Non-metastatic Ewing's sarcoma family of tumors of bone in adolescents and adults: prognostic factors and clinical outcome-single institution results.
There is limited data regarding outcomes of Ewing's sarcoma family of tumors in adolescents and adults compared with the same tumors in childhood. The aim of the study was to analyze prognostic factors and treatment results in a cohort of adolescents and adults with non-metastatic skeletal Ewing's sarcoma family of tumors. From 1992-2008, 90 adolescents and adults with Ewing's sarcoma family of tumors of the bone were referred to our institution. Sixty-five (72%) non-metastatic patients with analyzable data and treated in our institution were retrospectively evaluated. All patients were treated with alternated chemotherapy regimens administered every 3 weeks. The local treatment modality was selected according to tumor and patient characteristics. The median age was 21 years (range, 13-50). Most patients (74%) were >17 years of age. Forty-six percent of the tumors were located in the extremities. Local therapy was surgery in 45 patients and radiotherapy alone in 19 patients. Twenty-one patients received preoperative and 13 patients postoperative radiotherapy. Median follow-up was 43 months (range, 7-167). The 5-year event-free and overall survival rates for all patients were 44% and 49%, respectively. On univariate survival analysis, event-free and overall survival were worse for patients >17 years of age, tumor size >8 cm in diameter, an axial location, positive surgical margins, and poor histopathological response (<90% necrosis). Age, tumor site and tumor size on event-free and overall survival remained significant on multivariate analysis. We identified age, tumor size, and tumor site as independent prognostic factors, in accord with the Western literature. These patients require novel treatment modalities.


Installation of site-specific methylation into histones using methyl lysine analogs.
Chromatin structure is influenced by post-translational modifications on histones, the principal basic protein component of chromatin. In order to study one of these modifications, lysine methylation, in the context of reconstituted chromatin, this unit describes the installation of analogs of methyl lysine residues into recombinant histones. The modification site is specified by mutating the lysine of interest to cysteine. The mutant histones are expressed and purified, and the cysteine residue alkylated to produce N-methyl aminoethylcysteine, an isosteric analog of methyl lysine. Using different alkylating reagents, it is possible to install analogs of mono-, di-, or trimethyl lysine. While these analogs are not identical to methyl lysine residues, they show similar biochemical properties to their natural counterparts. The ease of synthesis of methyl lysine analog (MLA) histones, especially on a large scale, makes them particularly useful reagents for studying the effects of histone lysine methylation on chromatin structure, biophysics and biochemistry.


Curvature in metabolic scaling.
For more than three-quarters of a century it has been assumed that basal metabolic rate increases as body mass raised to some power p. However, there is no broad consensus regarding the value of p: whereas many studies have asserted that p is 3/4 (refs 1-4; 'Kleiber's law'), some have argued that it is 2/3 (refs 5-7), and others have found that it varies depending on factors like environment and taxonomy. Here we show that the relationship between mass and metabolic rate has convex curvature on a logarithmic scale, and is therefore not a pure power law, even after accounting for body temperature. This finding has several consequences. First, it provides an explanation for the puzzling variability in estimates of p, settling a long-standing debate. Second, it constitutes a stringent test for theories of metabolic scaling. A widely debated model based on vascular system architecture fails this test, and we suggest modifications that could bring it into compliance with the observed curvature. Third, it raises the intriguing question of whether the scaling relation limits body size.


Emerging polio-free zone--southern Africa, 1990-1994.
A key component of the global strategy to eradicate poliomyelitis by the year 2000 is surveillance for all cases of acute flaccid paralysis (AFP), ensuring the detection of cases of paralytic polio. During the 1990s, most of the countries of southern Africa (Table 1) have reported high (i.e., 70%-90%) levels of vaccination coverage among children aged < 1 year with three doses of oral poliovirus vaccine (OPV3). In addition, with the exception of Namibia, all of these countries have reported very low or zero incidence of polio (Table 1, Figure 1). To determine whether the low number of reported polio cases reflects the true incidence or underreporting, during 1992 and 1993 assessments of polio incidence and the quality of surveillance of suspected polio were conducted by teams consisting of national health officials, World Health Organization (WHO) staff and consultants, and representatives from Rotary International, using a standard protocol (1). This report summarizes the findings of assessments in Botswana, Lesotho, Malawi, South Africa, Swaziland, and Zimbabwe.


Perceived parental monitoring and health risk behavior among public secondary school students in El Salvador.
Although parental monitoring has received considerable attention in studies of U.S. adolescents, few published studies have examined how parents' knowledge of their children's whereabouts may influence health risk behaviors in adolescents living in Latin America. We investigated the association between perceived parental monitoring and substance use, fighting, and sexual behaviors in rural and urban Salvadoran adolescents (n = 982). After adjusting for several sociodemographic covariates, multilevel regression analyses indicated that students reporting low parental monitoring were between 2 to 3.5 times more likely to report risk behaviors examined. The promotion of specific parenting practices such as parental monitoring may hold promise for reducing adolescent risk behaviors in El Salvador.


GABA selectively increases mucin-1 expression in isolated pig jejunum.
The inhibitory neurotransmitter GABA (γ-aminobutyric acid) is synthesized by glutamic acid decarboxylase, which is expressed in the central nervous system and in various other tissues including the intestine. Moreover, GABA can be ingested in vegetarian diets or produced by bacterial commensals in the gastrointestinal tract. As previous studies in lung have suggested a link between locally increased GABA availability and mucin 5AC production, the present study sought to test whether the presence or lack of GABA (and its precursor glutamine) has an effect on intestinal mucin expression. Porcine jejunum epithelial preparations were incubated with two different amounts of GABA or glutamine on the mucosal side for 4 h, and changes in the relative gene expression of seven different mucins, enzymes involved in mucin shedding, GABA B receptor, enzymes involved in glutamine/GABA metabolism, glutathione peroxidase 2, and interleukin 10 were examined by quantitative PCR (TaqMan(®) assays). Protein expression of mucin-1 (MUC1) was analyzed by Western blot. On the RNA level, only MUC1 was significantly up-regulated by both GABA concentrations compared with the control. Glutamine-treated groups showed the same trend. On the protein level, all treatment groups showed a significantly higher MUC1 expression than the control group. We conclude that GABA selectively increases the expression of MUC1, a cell surface mucin that prevents the adhesion of microorganisms, because of its size and negative charge, and therefore propose that the well-described positive effects of glutamine on enterocytes and intestinal integrity are partly attributable to effects of its metabolite GABA.


[EFFICACY OF CYTOFLAVIN IN COMPLEX TREATMENT OF DIABETIC FOOT SYNDROME].
The study involved 97 patients with severe diabetic foot syndrome (DFS) subcompensated type 2 diabetes. All patients were available mediacalcification foot and lower leg arteries of different severity. Depending on the treatment, all patients were divided into 2 groups by stratified randomization. The І group received standard therapy, which is indicated for the DFS. A ІІ group of patients additionally received basic therapy drug Cytoflavin 10 ml 0,9% NaCl 200 ml for 10 days, followed by transfer to tablet form Cytoflavin 2 tablets 2 times per day orally for one month. We noted a positive trend of treatment of patients who, in addition to standard therapy received the drug Cytoflavin. Thus, the use of complex surgical treatment of patients with mixed form of DFS Cytoflavin reduces the severity of distal polyneuropathy, improves oxygenation of tissues and restores the enzyme activity of antioxidant system, that manifested neuroprotective, antioxidant and anti-hypoxic effects of drugs, which substantiates the indications for its use in the this pathology.


Maxillofacial-Derived Mesenchymal Stem Cells: Characteristics and Progress in Tissue Regeneration.
Maxillofacial-derived mesenchymal stem cells (MFSCs) are a particular collective type of mesenchymal stem cells (MSCs) that originate from the hard and soft tissue of the maxillofacial region. Recently, many types of MFSCs have been isolated and characterized. MFSCs have the common characteristics of being extremely accessible and amazingly multipotent and thus have become a promising stem cell resource in tissue regeneration. However, different MFSCs can give rise to different cell lineages, have different advantages in clinical use, and regulate the immune and inflammation microenvironment through paracrine mechanisms in different ways. Hence, in this review, we will concentrate on the updated new findings of all types of MFSCs in tissue regeneration and also introduce the recently discovered types of MFSCs. Important issues about proliferation and differentiation in vitro and in vivo, up-to-date clinical application, and paracrine effect of MFSCs in tissue regeneration will also be discussed. Our review may provide a better guide for the clinical use of MFSCs and further direction of research in MFSC regeneration medicine.


Interleukin-4 receptor-targeted liposomal doxorubicin as a model for enhancing cellular uptake and antitumor efficacy in murine colorectal cancer.
Our previous studies showed that colorectal tumor has high interleukin-4 receptor α (IL-4Rα) expression, whereas adjacent normal tissue has low or no IL-4Rα expression. We also observed that human atherosclerotic plaque-specific peptide-1 (AP1) can specifically target to IL-4Rα. In this study, we investigated the therapeutic efficacy and systemic toxicity of AP1-conjuagted liposomal doxorubicin. AP1 bound more strongly to and was more efficiently internalized into IL-4Rα-overexpressing CT26 cells than CT26 control cells. Selective cytotoxicity experiment revealed that AP1-conjugated liposomal doxorubicin preferentially killed IL-4Rα-overexpressing CT26 cells. AP1-conjugated liposomal doxorubicin administered intravenously into mice produced significant inhibition of tumor growth and showed decreased cardiotoxicity of doxorubicin. These results indicated that AP1-conjugated liposomal doxorubicin has a potent and selective anticancer potential against IL-4Rα-overexpressing colorectal cancer cells, thus providing a model for targeted anticancer therapy.


Overexpression of sphingosine kinase 1 is predictive of poor prognosis in human breast cancer.
Sphingosine kinase 1 (SPHK1) is a bioactive lipid mediator that has been identified as a biomarker in various cancers and is considered to play an important role in tumor progression. In the present study, the expression level of SPHK1 was examined in breast cancer clinical specimens, and its association with patient survival was investigated to clarify the clinical significance of SPHK1 in breast cancer. SPHK1 mRNA expression was increased in breast cancer tissues compared with that in matched adjacent breast tissues in 19 of 32 paired tissue specimens (59.4%). Immunohistochemical analysis of 122 breast cancer cases revealed that the expression levels of SPHK1 were upregulated in 64 tumor tissues (52.5%), and increased expression levels of the protein were significantly associated with the presence of lymph node metastasis (P=0.0016), number of positive lymph nodes (P=0.0268) and presence of distant metastasis (P=0.0097). Increased SPHK1 protein expression was also associated with human epidermal growth factor receptor 2 status (P=0.0100), initial symptoms (P=0.0025) and tumor location (P=0.0457). Patients with increased SPHK1 protein expression had shorter overall survival and disease-free survival times compared with patients with lower SPHK1. Univariate and multivariate analyses indicated that high SPHK1 expression may be a poor prognostic factor. These results indicated that SPHK1 may perform an important role in breast cancer and may be a predictive factor in patients with breast cancer.


Prosthetic Rehabilitation of a Patient Diagnosed With Sarcoidosis Using Dental Implants: A Clinical Case Report.
No previously published studies have reported on the placement and restoration of dental implants in a patient diagnosed with sarcoidosis. Patients with sarcoidosis may develop periodontitis as a manifestation of systemic disease and are therefore at increased risk of tooth loss. These patients are likely to want fixed dental prostheses, which may need to be supported by dental implants. The case presented is that of a 31-year-old female patient presenting with a missing maxillary central incisor and a sarcoidal process affecting the anterior maxilla, which had severely compromised the periodontium of the adjacent lateral incisor. The patient was successfully rehabilitated with an implant-retained prosthesis following a staged horizontal and vertical bone augmentation procedure. At the 4-year review, the implant restoration performed well with stable peri-implant bone levels. We conclude that dental implant rehabilitation in patients with sarcoidosis may be a predictable treatment option, depending on disease stability and concurrent systemic therapy, but these patients will require additional maintenance because of the possibility of an increased risk of peri-implantitis. The effects of sarcoidosis and its management on the success of dental implants are discussed to aid treatment planning for such patients.


Pulmonary artery sarcoma: a rare cause of dyspnoea.
A 72-year-old woman with no significant medical history presented to the emergency room for severe dyspnoea. The initial clinical diagnosis was acute pulmonary embolism. Heparin infusion was initiated while awaiting a computed tomographic scan but the patient's condition deteriorated dramatically and stat echocardiogram showed tamponade. Post-evacuation echo showed a dilated right ventricle with pulmonary hypertension and obstruction of the right pulmonary artery by a homogeneous mass attached to the pulmonary artery, suggesting a tumour rather than a thrombus. Computed tomographic scan confirmed the presence of an obstructive mass with almost no perfusion of the right lung. The patient was referred to cardiac surgery and the mass was removed, with anatomo-pathological diagnosis of a typical pulmonary artery sarcoma. Unfortunately, the patient died a few days after surgery. Primary pulmonary artery sarcoma is a rare tumour that arises in the central pulmonary arteries. Clinical presentation is often attributed to other causes of pulmonary hypertension, like pulmonary embolism. Magnetic resonance imaging could help to distinguish a soft tissue mass from a thrombus but definitive diagnosis is almost always made at surgery or autopsy since patients usually present in acute and unstable situations. Prognosis is poor, from several months to a few years, and depends on how early the diagnosis is made, the presence of recurrence or metastasis after surgical resection, and the use of adjuvant therapy like radiation and chemotherapy.


Tuberculosis case burden and treatment outcomes in children, adults and older adults, Vanuatu, 2007-2011.
All five DOTS centres in Vanuatu. To determine across the age spectrum the tuberculosis (TB) case burden, disease pattern and treatment outcomes in patients registered between 2007 and 2011. Retrospective cohort study involving reviews of TB registers and treatment cards. Of 588 TB patients, 142 (24%) were children (aged 0-14 years), 327 (56%) adults (aged 15-54 years) and 119 (20%) were older adults (aged ⩾55 years; subdivided into 55-64 and ⩾65 years); 568 were new patients, 13 had been treated previously and 7 had unknown status. Compared with adults, children with new TB had a higher prevalence of extra-pulmonary TB (75% vs. 34%, OR 5.7, 95%CI 3.6-9.0) and a lower prevalence of smear-positive pulmonary TB (11% vs. 45%, OR 0.15, 95%CI 0.1-0.3), while older adults with new TB had a higher prevalence of smear-negative pulmonary TB (38% vs. 21%, OR 2.4, 95%CI 1.5-3.8). Overall TB treatment success was 83%, but in the second category of older adults (⩾65 years) treatment success was 67% and case fatality was 18%. Children and older adults constitute 45% of the TB burden in Vanuatu. Differences in disease patterns and poorer treatment outcomes in older adults have implications for policy and practice.


Technical note: bone marrow aspirate needle to assist in-situ screw fixation of slipped capital femoral epiphysis.
Slipped capital femoral epiphysis (SCFE) is characterized by posterior and inferior displacement of the capital femoral epiphysis in relationship to the metaphysis. Although universally accepted as a treatment modality for SCFE, in-situ pinning may be technically challenging in obese adolescents with large body habitus. Adequate screw position is important to achieve stabilization of the epiphysis and to allow closure of the growth plate. During the surgical procedure of in-situ pinning, it is crucial to obtain not only a perfect starting point but also an appropriate trajectory. However, creating a perfect entry point in obese patients with a large thigh may be troublesome. Often the pediatric orthopedic surgeon is faced with intraoperative challenges for screw placement including, but not limited to, the guidewire skiving down anteriorly on the metaphysis, and bending of the guidewire due to a large body habitus when the hip is positioned to obtain a lateral radiograph. We have used a bone marrow biopsy needle as an adjunct for placement of the guidewire during in-situ pinning for SCFE. This technical trick describes our method of using a bone marrow biopsy needle to ease the placement of a guidewire during in-situ pinning.


Cyclooxygenase Inhibition: Pain, Inflammation, and the Cardiovascular System.
Inhibitors of the cyclooxygenases (COXs), the nonsteroidal antiinflammatory drugs (NSAIDs), relieve inflammatory pain, but are associated with gastrointestinal and cardiovascular complications. Given the widespread use of NSAIDs, there has been a longstanding interest in optimizing their risk-benefit ratio, for example by reducing their gastrointestinal risk. More recently, the focus has shifted toward the cardiovascular complications of NSAIDs and very large prospective studies have been performed to compare cardiovascular risk across distinct NSAIDs. Surprisingly, much less attention has been paid to the efficacy side of the risk-benefit ratio. There is marked variability in the degree of pain relief by NSAIDs due to the complex interplay of molecular mechanisms contributing to the pain sensation, variability in the disposition of NSAIDs, and imprecision in the quantification of human pain. Here we discuss how NSAIDs relieve pain, how molecular mechanisms relate to clinical efficacy, and how this may inform our interpretation of clinical trials.


Maturational changes of effective elastance in the first 10 days of life.
The effective elastance of the respiratory system (E'rs) is a measure of its ability to resist a change in tidal volume under conditions of changing elastic loads. E'rs was measured while subjects breathed air and 2% CO2 and 4% CO2 in air in two groups of premature infants of different gestational ages at 1 day 3-4 days, and 7-10 days of age. E'rs was shown to decrease with increasing maturation and was independent of changes in control tidal volume. The decrease of E'rs with increased gestational age could be accounted for by differences in calculated thoracic gas volumes in all but one instance, where E'rs was lower in one group on the 3rd day of life. The activity of the Hering-Breuer reflex, as measured by the degree of slowing of inspiratory time after occlusion at FRC, has been previously reported to be normal to increased in similar infants. This suggests that differences related to size account for most of the maturational changes of E'rs in newborns.


Tuberculous aortitis in an human immunodeficiency virus-positive Ivorian migrant: A case report.
We report an unusual case of a 35-year-old Ivorian migrant with an abdominal mass and medical history relevant for human immunodeficiency virus-2 positivity with a CD4/CD8 ratio of 0.63; Mantoux and lymphocyte stimulation tests (QuantiFERON) were positive. 3D-CT images revealed a voluminous non-homogeneous retroperitoneal mass in the right abdominal region presenting no significant contrast impregnation. Thoraco-abdominal aorta presented diffuse-altered morphology with multiple ectasias throughout its course and an aneurysm at the level of the subrenal tract. The patient underwent vascular surgery. Mycobacterium tuberculosis complex was detected by polymerase chain reaction performed on intraoperative tissue specimens. Postoperative course was uneventful. After surgery, 3D-CT images showed no signs of malfunction of the prosthesis. At last, at 6-month follow-up, the patient was well. Cross-sectional imaging techniques, such as contrasted-CT, are essential and allow for making diagnosis, assessing disease activity, and evaluating post-treatment condition. 3D reconstruction permits an appropriate patient care by means of an excellent visualization and staging of the disease process.


A minor experimental stenosis in porcine descending thoracic aorta affects the spectral content of pressure pulse wave.
To carry out research into the possible changes of the spectral content of pressure pulse wave after the creation of an experimentally induced stenosis in the pig descending thoracic aorta. Eight healthy, normotensive Landrace pigs were subjected to thoracotomy under sterile conditions. At the upper segment of the descending thoracic aorta, a 5-mm-long circumferential symmetric constriction was imposed and stabilized; hence, a 15-20 mm Hg pressure gradient was established. Pressure tip catheters were used in order to monitor the pressure gradient. Blood flow disturbances were recorded through a bidirectional Doppler flow meter at pre- and poststenotic areas (A and B, respectively). Measurements were carried out before, 10 min after, and 90 days after the creation of the stenosis. The recorded waveforms were analyzed mathematically by using Fourier Transform, in order to determine their spectral component. Eight sham-operated pigs were used as controls. Fourier Transform analysis showed a significant increase (P < 0.05) of spectral content in A and B areas. Also, the "relative" harmonic amplitudes in nonstenotic subjects were higher than in stenotic animals (P < 0.05). A minor experimental constriction located at the level of the descending thoracic aorta increased the spectral content of the pressure pulse wave, indicating that spectral analysis may detect slight flow disturbances before developing remarkable signs of an impaired circulation system.


Chromatic aberration effect on solar energy systems using Fresnel lenses.
In concentration systems using Fresnel lenses the effect of the chromatic aberration can become important. In this paper we propose a method to take this effect into account for designing purposes. Also we define a parameter that allows one to estimate the degradation of the thermodynamic quality of the concentrator due to this effect. This parameter follows a hyperbolic law, with the acceptance angle showing that it is important to consider chromatic aberration when modeling concentrators with a high concentration factor. However, this complexity is unnecessary for moderate or low concentration factors.


Consensus statement: Safe Airway Society principles of airway management and tracheal intubation specific to the COVID-19 adult patient group.
This statement was planned on 11 March 2020 to provide clinical guidance and aid staff preparation for the coronavirus disease 2019 (COVID-19) pandemic in Australia and New Zealand. It has been widely endorsed by relevant specialty colleges and societies. Generic guidelines exist for the intubation of different patient groups, as do resources to facilitate airway rescue and transition to the "can't intubate, can't oxygenate" scenario. They should be followed where they do not contradict our specific recommendations for the COVID-19 patient group. Consideration should be given to using a checklist that has been specifically modified for the COVID-19 patient group. Early intubation should be considered to prevent the additional risk to staff of emergency intubation and to avoid prolonged use of high flow nasal oxygen or non-invasive ventilation. Significant institutional preparation is required to optimise staff and patient safety in preparing for the airway management of the COVID-19 patient group. The principles for airway management should be the same for all patients with COVID-19 (asymptomatic, mild or critically unwell). Safe, simple, familiar, reliable and robust practices should be adopted for all episodes of airway management for patients with COVID-19. Airway clinicians in Australia and New Zealand should now already be involved in regular intensive training for the airway management of the COVID-19 patient group. This training should focus on the principles of early intervention, meticulous planning, vigilant infection control, efficient processes, clear communication and standardised practice.


Intensive consolidation with G-CSF support: Tolerability, safety, reduced hospitalization, and efficacy in acute myeloid leukemia patients ≥60 years.
The aim of this study was to evaluate the efficacy and feasibility of intensified consolidation therapy employing fludarabine and ARA-C in cycle 1 and intermediate-dose ARA-C (IDAC) in cycles 2 through 4, in elderly acute myeloid leukemia (AML) patients and to analyze the effects of pegfilgrastim on the duration of neutropenia, overall toxicity, and hospitalization-time during consolidation in these patients. Thirty nine elderly patients with de novo AML (median age 69.9 years) who achieved complete remission (CR) after induction-chemotherapy were analyzed. To examine the effect of pegfilgrastim on neutropenia and hospitalization, we compared cycles 2 and 4 where pegfilgrastim was given routinely from day 6 (IDAC-P) with cycle 3 where pegfilgrastim was only administered in case of severe infections and/or prolonged neutropenia. All four planned cycles were administered in 23/39 patients (59.0%); 5/39 patients (12.8%) received 3 cycles, 3/39 (7.7%) 2 cycles, and 8/39 (20.5%) one consolidation-cycle. The median duration of severe neutropenia was 7 days in cycle 2 (IDAC-P), 11.5 days in cycle 3 (IDAC), and 7.5 days in cycle 4 (IDAC-P) (P < .05). Median overall survival was 1.1 years and differed significantly between patients aged <75 and ≥75 years (P < .05). The probability to be alive after 5 years was 32%. Together, intensified consolidation can be administered in AML patients ≥60, and those who are <75 may benefit from this therapy. Routine administration of pegfilgrastim during consolidation shortens the time of neutropenia and hospitalization in these patients.


Hypoxia induces hypersensitivity and hyperreactivity to thromboxane receptor agonist in neonatal pulmonary arterial myocytes.
PPHN, caused by perinatal hypoxia or inflammation, is characterized by an increased thromboxane-prostacyclin ratio and pulmonary vasoconstriction. We examined effects of hypoxia on myocyte thromboxane responsiveness. Myocytes from 3rd-6th generation pulmonary arteries of newborn piglets were grown to confluence and synchronized in contractile phenotype by serum deprivation. On the final 3 days of culture, myocytes were exposed to 10% O2 for 3 days; control myocytes from normoxic piglets were cultured in 21% O2. PPHN was induced in newborn piglets by 3-day hypoxic exposure (Fi(O2) 0.10); pulmonary arterial myocytes from these animals were maintained in normoxia. Ca2+ mobilization to thromboxane mimetic U-46619 and ATP was quantified using fura-2 AM. Three-day hypoxic exposure in vitro results in increased basal [Ca2+]i, faster and heightened peak Ca2+ response, and decreased U-46619 EC50. These functional changes persist in myocytes exposed to hypoxia in vivo but cultured in 21% O2. Blockade of Ca2+ entry and store refilling do not alter peak U-46619 Ca2+ responses in hypoxic or normoxic myocytes. Blockade of ryanodine-sensitive or IP3-gated intracellular Ca2+ channels inhibits hypoxic augmentation of peak U-46619 response. Ca2+ response to ryanodine alone is undetectable; ATP-induced Ca2+ mobilization is unaltered by hypoxia, suggesting no independent increase in ryanodine-sensitive or IP3-linked intracellular Ca2+ pool mobilization. We conclude hypoxia has a priming effect on neonatal pulmonary arterial myocytes, resulting in increased resting Ca2+, thromboxane hypersensitivity, and hyperreactivity. We postulate that hypoxia increases agonist-induced TP-R-linked IP3 pathway activation. Myocyte thromboxane hyperresponsiveness persists in culture after removal from the initiating hypoxic stimulus, suggesting altered gene expression.


Addition of IFN-alpha to treatment of malignant brain tumors.
Despite many attempts to improve the survival after surgery of patients with malignant astrocytoma the prognosis is poor. We have used natural IFN-alpha in 16 patients with malignant astrocytoma treated between 1987 and 1990; 6 for recurrent tumors. Radiation therapy was given in 2 Gy fractions daily to a total dose of 50 Gy in the tumor area, 5 fractions per week and IFN twice per week, cisplatinum 60 mg/m2 i.v. every second week and vincristine 2 mg every week in 12-h i.v. infusions. Eight patients were reoperated when clinical deterioration suggested recurrent tumor; histological examination showed no residual tumor in 7 of them. Of these 8 patients 3 are alive and well, 2 of them after more than 5 years. The study suggests that malignant astrocytoma can be successfully eradicated with surgery, irradiation, IFN-alpha and chemotherapy. The treatment had, however, unacceptably high neurotoxicity. Earlier removal of the tumor necrosis, before clinical deterioration, could possibly diminish the high complication rate and consequently improve survival.


Interrenal responses to high ambient temperature in soft-shelled turtle, Lissemys punctata punctata.
An exposure to ambient temperature of 25 degrees C had no perceptible effect on interrenal function but further increase of temperature to 35 degrees C caused nuclear hypertrophy with increase of nuclear diameter, RNA concentration, acid phosphatase and alkaline phosphatase activities, accompanied by quantitative depletions of cholesterol (free, esterified and total) and ascorbic acid levels in the interrenal gland of the soft-shelled turtle Lissemys p. punctata. Similar manifestations of stimulation, except in the nucleus, were marked after exposure to 38 degrees C, but the degree of response in respect of esterified and free cholesterol levels was higher at 38 degrees C than at 35 degrees C. Moreover, withdrawal of 38 degrees C temperature and subsequently maintaining at 25 degrees C for 15 days showed reverse manifestations to those of 35 degrees C/38 degrees C, leading to a tendency towards normalcy. It is suggested that high a ambient temperature of 35 degrees C significantly stimulates interrenal function of Lissemys turtles, but further increase of 38 degrees C does not cause further overall stimulation, and withdrawal of higher temperature (38 degrees C) shows a tendency towards normalcy. It is also suggested that (a) high ambient temperature causes thermal stress, (b) it is reversible and (c) it acts on interrenal activity presumably via CRF-ACTH-axis in turtles.


Low- to high-throughput analysis of telomerase modulators with Telospot.
We designed a method termed Telospot to discover and characterize telomerase modulators as anticancer drugs or chemical biology tools. Telospot is based on a highly efficient human telomerase expression system and the detection of telomerase DNA reaction products in macroarray format. Telospot offers a highly scalable, cost- and time-effective alternative to presently available telomerase assays, which are limited by the requirement for PCR, telomerase purification or technologies not amenable to high throughput.


Induction of monocyte chemoattractant protein-1 (MCP-1/CCL2) gene expression by human immunodeficiency virus-1 Tat in human astrocytes is CDK9 dependent.
Human immunodeficiency virus-1 (HIV-1) invades the brain early in infection and may cause HIV-associated dementia (HAD), which is characterized by reactive astrocytes, and macrophage and T-cell infiltrates. HIV-1 Tat protein is thought to contribute to HAD by transactivating host genes, such as that encoding monocyte chemoattractant protein-1 (MCP-1/CCL2), although its mechanisms of action are not fully understood. We investigated the molecular pathways involved in Tat-induced MCP-1/CCL2 gene expression in human astrocytes. We found that Tat induced MCP-1/CCL2 synthesis in human astrocytes infected with a lentivirus carrying the gene encoding Tat or treated with a biologically active synthetic Tat protein. The induction of MCP-1/CCL2 was independent of the nuclear factor kappaB (NF-kappaB) classical pathway, but was significantly inhibited by specific cyclin-dependent kinase 9 (cdk9) inhibitors, such as a dominant-negative mutant or siRNA. By contrast, broader-spectrum cdk inhibitors, such as roscovitine, 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole (DRB), and flavopiridol, inhibited MCP-1/CCL2 induction by Tat. We also analyzed the effects of roscovitine, DRB, and flavopiridol on Tat-induced HIV-1 long terminal repeat (LTR) expression following the infection of astrocytes and HeLa cells. Astrocytes showed no inhibition by roscovitine, 59% inhibition by DRB, and 80% inhibition by flavopiridol. In control HeLa cells, high levels of inhibition were observed with roscovitine, DRB, and flavopiridol. We have ascertained the direct implication of cdk9 in Tat-induced MCP-1 expression by performing ChIP assay. These results demonstrate that cdk9 is involved in Tat-induced HIV-1 LTR, MCP-1/CCL2 gene expression.


Dehydrogenative Annulation of Silylated 1H-Indoles with Alkynes via Silyl Migration.
We investigated the dehydrogenative annulation of silylated 1H-indole derivatives with alkynes to synthesize a silole-fused indole. The addition of the in situ generated silylium ion to alkynes was followed by the sila-Friedel-Crafts reaction via silyl migration, realizing regioselective dehydrogenative annulation controlled by the steric bulkiness of a base. The optical properties of the obtained siloloindoles indicated fluorescence of which the intensity depends on the location of the fused silole.


Date palm pollen allergoid: characterization of its chemical-physical and immunological properties.
Date palm (DP) pollen can cause allergic symptoms in people living in different countries. Specific immunotherapy with allergenic extracts by subcutaneous route is effective to cure allergic people. However, the risk of side effects has led to explore safer therapeutic modalities. The aim of our work was to evaluate IgE cross-reactivity between DP and autochthonous palm (European fan palm, EFP) pollen extracts, to chemically modify DP extract with potassium cyanate in order to obtain an allergoid, and to characterize it. By radioallergosorbent test inhibition, immunoblotting (IB) and skin prick test, in vitro and in vivo allergenic activities of native and modified DP extracts were compared. By SDS-PAGE and IB, we compared the protein profile and IgE-binding capacity of both native and modified DP, as well as of EFP extracts. By IB inhibition, IgE cross-reactivity of native DP and EFP extracts was evaluated. By ELISA, the capacity of modified DP-induced IgG to react with native DP extract was determined. Radioallergosorbent test inhibition, IB and skin prick test results demonstrated that modified DP was significantly less allergenic than native DP extract. The SDS-PAGE profile showed that potassium cyanate treatment of DP extract did not alter the molecular weight of its components. In addition, no difference was observed between native DP and EFP extracts. Subsequent IB inhibition data evidenced the existence of a strong IgE cross-reactivity between native DP and EFP extracts. ELISA results indicated that the administration of modified DP in mice was able to induce specific IgG also recognizing native DP extract. Modified DP extract (allergoid) seems to be a good candidate for immunotherapy of patients affected by specific allergy.


Pediatric Spine Trauma: A Brief Review.
Pediatric spinal trauma is a broad topic with nuances specific to each anatomic region of the spinal column. The purpose of this report is to provide a brief review highlighting the most important and common clinical issues regarding the diagnosis and management of pediatric spine trauma. Detailed descriptions of imaging findings along with specific operative and nonoperative management of each fracture and dislocation type are beyond the scope of this review.


Protecting the unborn clone: can law and science evolve together?
The courts have treated the unborn child as neither person nor property. Human cloning will challenge this legal principle. Human cloning provides options for future scientific development and treatment of disease and infertility. However, cloning gives rise to issues not yet considered, in law, let alone resolved. These issues are not present in the context of normal human birth. At present, the common law restricts its scope to normal human birth. Does the donor "own" their unborn clone? Who makes decisions on behalf of the unborn clone? The gap between science and law is too large in human cloning research. Law lags behind in adapting to new technologies. This paper will address legal issues in relation to the unborn clone. Cloning will challenge the law in its current state. Decision-making and control of the unborn child are vital issues, to be determined before human cloning can be permitted to take place. The individuals who might have an interest in the unborn clone include the donor, the scientist, who either developed the finished clone or stored the clone prior to implantation, and the surrogate mother. Claims or conflicts might arise in many areas of medicine and law. Does the scientist have an intellectual property right? Can the surrogate mother terminate the pregnancy at will? If the unborn clone is not aborted, what measures are required to protect the fetus? Can the surrogate mother be liable for neglect? Who decides about disclosure of information and knowledge or choice regarding fetal diagnosis and treatment? Who has custody of the unborn clone? In this paper, the concepts of trusts are explored to develop a means of resolving conflicts among the individuals who might claim an interest in the unborn clone. The trust doctrine is flexible and may be useful in resolving claims or conflicts.


Immobilization of Aspergillus niger NRC 107 Xylanase and beta-Xylosidase, and Properties of the Immobilzed Enzymes.
Aspergillus niger NRC 107 xylanase and beta-xylosidase were immobilized on various carriers by different methods of immobilization, including physical absorption, covalent binding, ionic binding, and entrapment. The immobilized enzymes were prepared by physical adsorption on tannin-chitosan, ionic binding onto Dowex-50W, covalent binding on chitosan beads through glutaraldehyde, and entrapment in polyacrylamide had the highest activities. In most cases, the optimum pH of the immobilized enzymes were shifted to lower than those of free enzymes. The optimum reaction temperature of immobilized xylanase was shifted from 50C to 52.5-65C, whereas that of immobilized beta-xylosidase was shifted from 45C to 50-60C. The Km values of immobilized enzymes were higher than those of native enzymes. The operational stability of the immobilized enzymes was evaluated in continuous operation in packed-bead column-type reactors. The enzymes covalently bounded to chitosan showed the highest operational stability. However, the enzymes immobilized by physical absorption or by ionic binding showed a low operational stability. The enzymes entrapped in polyacrylamide exhibited lower activity, but better operational stability.


Reading speed and phonological awareness deficits among Arabic-speaking children with dyslexia.
Although reading accuracy of isolated words and phonological awareness represent the main criteria of subtyping developmental dyslexia, there is increasing evidence that reduced reading speed also represents a defining characteristic. In the present study, reading speed and accuracy were measured in Arabic-speaking phonological and mixed dyslexic children matched with controls of the same age. Participants in third and fourth grades, aged from 9-10 to 9-8 years, were given single frequent and infrequent word and pseudo-word reading and phonological awareness tasks. Results showed that the group with dyslexia scored significantly lower than controls in accuracy and speed in reading tasks. Phonological and mixed dyslexic subgroups differed in infrequent and frequent word reading accuracy, the latter being worse. In contrast, the subgroups were comparable in pseudo-word identification and phonological awareness. Delayed phonological and recognition processes of infrequent and frequent words, respectively, were placed in the context of the dual route model of reading and the specific orthographic features of the Arabic language.


Sleep-dependent activity of T cells and regulatory T cells.
A number of immunological functions are dependent on circadian rhythms and regular sleep. This has impact on the type and magnitude of immune responses following antigenic challenge, for example in vaccination. Little is known about the underlying mechanisms. One possibility may be the circadian and sleep-dependent modulation of CD4(+)CD25(-) T cell responses by CD4(+)CD25(+) natural regulatory T cells (nT(reg)). In a variety of studies, nT(reg) have been shown to regulate T cell responses negatively. Thus, we investigated the influence of sleep and circadian rhythm on the number and function of nT(reg) as well as on the function of CD4(+)CD25(-) T cells. Seven healthy young men were examined under defined conditions on two occasions, i.e. during sleep and sleep deprivation. Venous blood was drawn periodically; numbers of nT(reg), suppressive activity of nT(reg), interleukin-2 production and proliferation of CD4(+)CD25(-) T cells were explored in vitro. nT(reg) counts revealed a significant circadian rhythm with highest levels during the night (mean 95 nT(reg)/microl) and lowest levels during the day (mean 55 nT(reg)/microl). During normal sleep, the suppressive activity of nT(reg) was highest at 02.00 h and somewhat lower at 15.00 h. Surprisingly, almost no suppressive activity was present at 07.00 h. Deprivation of sleep abrogated this rhythm. CD4(+)CD25(-) T cell proliferation was dampened significantly by sleep deprivation. This is the first study in human cells to show that nT(reg) number and function follow a rhythm across the 24-h period. Furthermore, sleep deprivation severely disturbs the functional rhythm of nT(reg) and CD4(+)CD25(-) T cells.


A potassium-39 NMR study of potassium binding to double-helical DNA.
The binding of K+ to double-helical DNA has been examined by 39K NMR. The results obtained are in substantial agreement with previous measurements of 23Na+ binding to DNA. Thus, in both cases the fractional neutralization of DNA phosphate charge appears independent of the total univalent cation concentration. Further, the dependences of the 23Na+ and 39K+ linewidths on Mg2+ and on temperature are strikingly similar. The implications of these results are discussed in terms of current theories of counterion binding to cylindrical polyelectrolytes.


Constructing abortion as a social problem: "Sex selection" and the British abortion debate.
Between February 2012 and March 2015, the claim that sex selection abortion was taking place in Britain and that action needed to be taken to stop it dominated debate in Britain about abortion. Situating an analysis in sociological and social psychological approaches to the construction of social problems, particularly those considering "feminised" re-framings of anti-abortion arguments, this paper presents an account of this debate. Based on analysis of media coverage, Parliamentary debate and official documents, we focus on claims about grounds (evidence) made to sustain the case that sex selection abortion is a British social problem and highlight how abortion was problematised in new ways. Perhaps most notable, we argue, was the level of largely unchallenged vilification of abortion doctors and providers, on the grounds that they are both law violators and participants in acts of discrimination and violence against women, especially those of Asian heritage. We draw attention to the role of claims made by feminists in the media and in Parliament about "gendercide" as part of this process and argue that those supportive of access to abortion need to critically assess both this aspect of the events and also consider arguments about the problems of "medical power" in the light of what took place.


[Phenylpropanoid amides from whole plants of Corydalis edulis].
Ten phenylpropanoid amides were isolated from the whole plants of Corydalis edulis Maxim. by various of column chromatographies including silica gel, Sephadex LH-20, and ODS. Their structures were identified on the basis of physicochemical properties, MS, NMR, and IR spectroscopic data. These compounds were identified as N-trans-sinapoyl-3-methoxytyramine-4'-O-β-glucoside(1), N-trans-sinapoyl-3-methoxytyramine(2), N-trans-sinapoyltyramine(3), N-trans-p-coumaroyltyramine(4), N-trans-sinapoyl-7-hydroxytyramine(5), N-cis-feruloyltyramine(6), N-cis-p-coumaroyltyramine(7), N-trans-feruloyltyramine(8), N-trans-feruloyl-3-methoxytyramine(9), and N-trans-feruloyl-7-hydroxytyramine(10). Compound 1 is a new compound. Compounds 2-7 are obtained from the plants of Papaveraceae for the first time, while compounds 8-10 are firstly isolated from C. edulis.


Prognostic psychosocial factors for disabling low back pain in Japanese hospital workers.
Although the occupational health field has identified psychosocial factors as risk factors for low back pain that causes disability, the association between disabling low back pain and psychosocial factors has not been examined adequately in Japanese hospital workers. Therefore, this study examined the association between low back pain, which interfered with work, and psychosocial factors in Japanese hospital workers. This cross-sectional study was conducted at a hospital in Japan. In total, 280 hospital workers were recruited from various occupational settings. Of these, 203 completed a self-administered questionnaire that included items concerning individual characteristics, severity of low back pain, fear-avoidance beliefs (Fear-Avoidance Beliefs Questionnaire), somatic symptoms (Somatic Symptom Scale-8), psychological distress (K6), workaholism, and work-related psychosocial factors (response rate: 72.5%). Logistic regression was used to explore risk factors associated with disabling low back pain. Of the 203 participants who completed questionnaires, 36 (17.7%) reported low back pain that interfered with their work. Multivariate analyses with individual factors and occupations adjusted for showed statistically significant associations between disabling low back pain and fear-avoidance beliefs (adjusted odds ratio [OR]: 2.619, 95% confidence interval [CI]: 1.003-6.538], somatic symptoms (OR: 4.034, 95% CI: 1.819-9.337), and interpersonal stress at work (OR: 2.619, 95% CI: 1.067-6.224). Psychosocial factors, such as fear-avoidance beliefs, somatic symptoms, and interpersonal relationships at work, were important risk factors in low back pain that interfered with work in Japanese hospital workers. With respect to occupational health, consideration of psychosocial factors is required to reduce disability related to low back pain.


Clinical and Histopathological Findings of Frontal Fibrosing Alopecia-Associated Lichen Planus Pigmentosus.
Frontal fibrosing alopecia (FFA) is a primary lymphocytic scarring alopecia occurring mainly in postmenopausal women. A range of facial lesions have been described in FFA, such as lichen planus (LP) pigmentosus, red dots, facial papules, and perifollicular and diffuse erythema. These lesions can be the first sign of FFA. LP pigmentosus is a rare variant of LP. The first description of LP pigmentosus associated with FFA (in 2012) reported 22 cases of LP pigmentosus among 44 cases of FFA affecting South African patients. We reviewed 16 FFA patients with LP pigmentosus and the histopathological findings of the biopsy of LP pigmentosus in 9 patients. Most patients had intermediate skin phototypes (III-IV; n = 10; 62%). The age at onset of LP pigmentosus ranged from 30 to 60 years. The most common histopathological findings were epidermal atrophy, basal cell degeneration, interfollicular inflammatory infiltrate and melanophages, and perifollicular changes. Other findings not previously described in LP pigmentosus were inflammation and interface changes on sweat duct epithelia (acrosyringium and superior dermal duct), and lichenoid perisebaceitis. Histology of our cases confirmed previous findings and showed a high incidence of perifollicular involvement with occasional changes affecting sebaceous and sweat glands.


Serum and urine levels of levocarnitine family components in genetically diabetic rats.
Serum concentration and urinary excretion of levocarnitine (L-carnitine, CAS 541-15-1) family components were evaluated in a Wistar derived strain of genetically diabetic rats BB/BB, in comparison with normal Wistar rats, and their control rats BB/WB of both sexes. BB/BB diabetic animals have lower serum concentration of total-L-carnitine (TC), L-carnitine (LC), acetyl-L-carnitine (ALC), and short chain L-carnitine esters (SCLCE) than both the strains of non-diabetic rats, as previously observed in streptozotocin diabetic rats. No or marginal variations between control and diabetic rats were detected in cumulative urinary excretion of L-carnitine family components. A strain difference was observed between Wistar and BB/WB non-diabetic rats, BB/WB showing higher serum concentration and lower cumulative urinary excretion of LC and TC than Wistar animals. Renal clearance of L-carnitine components proved to be markedly higher in BB/BB diabetic rats, as previously shown in streptozotocin rats. The reduction of serum concentration of the carnitines endogenous pool may explain this finding. The lack of an increased urinary excretion of L-carnitine components in diabetic animals despite the high increase of diuresis suggests that the saturable tubular reabsorption of L-carnitine family components also in diabetes is the primary mechanism to preserve the homeostatic equilibria of the L-carnitine family, the variation in serum concentration being attributable to the complex systemic metabolic alterations typical of diabetes. In agreement with previous investigations, male animals of all the strains showed higher serum concentration and urinary excretion of L-carnitine components as compared to females.


T cell receptor gamma-chain gene polymerase chain reaction to diagnose central nervous system involvement by cutaneous T cell lymphoma.
The authors describe a patient who was suspected of having cutaneous T cell lymphoma involvement of the brain despite repeatedly negative cerebrospinal fluid (CSF) cytology, inconclusive flow cytometry, and no discrete lesion for brain biopsy. The diagnosis was made by polymerase chain reaction (PCR) analysis that showed a monoclonal T cell receptor gamma-chain gene rearrangement in the CSF, identically sized to that present in a skin biopsy specimen. Thus, PCR could be used early and routinely to diagnose central nervous system spread of T cell lymphomas, because of its potentially superior sensitivity and specificity to CSF cytology.


Does this dyspneic patient in the emergency department have congestive heart failure?
Dyspnea is a common complaint in the emergency department where physicians must accurately make a rapid diagnosis. To assess the usefulness of history, symptoms, and signs along with routine diagnostic studies (chest radiograph, electrocardiogram, and serum B-type natriuretic peptide [BNP]) that differentiate heart failure from other causes of dyspnea in the emergency department. We searched MEDLINE (1966-July 2005) and the reference lists from retrieved articles, previous reviews, and physical examination textbooks. We retained 22 studies of various findings for diagnosing heart failure in adult patients presenting with dyspnea to the emergency department. Two authors independently abstracted data (sensitivity, specificity, and likelihood ratios [LRs]) and assessed methodological quality. Many features increased the probability of heart failure, with the best feature for each category being the presence of (1) past history of heart failure (positive LR = 5.8; 95% confidence interval [CI], 4.1-8.0); (2) the symptom of paroxysmal nocturnal dyspnea (positive LR = 2.6; 95% CI, 1.5-4.5); (3) the sign of the third heart sound (S(3)) gallop (positive LR = 11; 95% CI, 4.9-25.0); (4) the chest radiograph showing pulmonary venous congestion (positive LR = 12.0; 95% CI, 6.8-21.0); and (5) electrocardiogram showing atrial fibrillation (positive LR = 3.8; 95% CI, 1.7-8.8). The features that best decreased the probability of heart failure were the absence of (1) past history of heart failure (negative LR = 0.45; 95% CI, 0.38-0.53); (2) the symptom of dyspnea on exertion (negative LR = 0.48; 95% CI, 0.35-0.67); (3) rales (negative LR = 0.51; 95% CI, 0.37-0.70); (4) the chest radiograph showing cardiomegaly (negative LR = 0.33; 95% CI, 0.23-0.48); and (5) any electrocardiogram abnormality (negative LR = 0.64; 95% CI, 0.47-0.88). A low serum BNP proved to be the most useful test (serum B-type natriuretic peptide <100 pg/mL; negative LR = 0.11; 95% CI, 0.07-0.16). For dyspneic adult emergency department patients, a directed history, physical examination, chest radiograph, and electrocardiography should be performed. If the suspicion of heart failure remains, obtaining a serum BNP level may be helpful, especially for excluding heart failure.


Functional Relationship between Osteogenesis and Angiogenesis in Tissue Regeneration.
Bone tissue renewal can be outlined as a complicated mechanism centered on the interaction between osteogenic and angiogenic events capable of leading to bone formation and tissue renovation. The achievement or debacle of bone regeneration is focused on the primary role of vascularization occurrence; in particular, the turning point is the opportunity to vascularize the bulk scaffolds, in order to deliver enough nutrients, growth factors, minerals and oxygen for tissue restoration. The optimal scaffolds should ensure the development of vascular networks to warrant a positive suitable microenvironment for tissue engineering and renewal. Vascular Endothelial Growth Factor (VEGF), a main player in angiogenesis, is capable of provoking the migration and proliferation of endothelial cells and indirectly stimulating osteogenesis, through the regulation of the osteogenic growth factors released and through paracrine signaling. For this reason, we concentrated our attention on two principal groups involved in the renewal of bone tissue defects: the cells and the scaffold that should guarantee an effective vascularization process. The application of Mesenchymal Stem Cells (MSCs), an excellent cell source for tissue restoration, evidences a crucial role in tissue engineering and bone development strategies. This review aims to provide an overview of the intimate connection between blood vessels and bone formation that appear during bone regeneration when MSCs, their secretome-Extracellular Vesicles (EVs) and microRNAs (miRNAs) -and bone substitutes are used in combination.


High sensitivity X-ray phase contrast imaging by laboratory grating-based interferometry at high Talbot order geometry.
X-ray phase contrast imaging is a powerful analysis technique for materials science and biomedicine. Here, we report on laboratory grating-based X-ray interferometry employing a microfocus X-ray source and a high Talbot order (35th) asymmetric geometry to achieve high angular sensitivity and high spatial resolution X-ray phase contrast imaging in a compact system (total length <1 m). The detection of very small refractive angles (∼50 nrad) at an interferometer design energy of 19 keV was enabled by combining small period X-ray gratings (1.0, 1.5 and 3.0 µm) and a single-photon counting X-ray detector (75 µm pixel size). The performance of the X-ray interferometer was fully characterized in terms of angular sensitivity and spatial resolution. Finally, the potential of laboratory X-ray phase contrast for biomedical imaging is demonstrated by obtaining high resolution X-ray phase tomographies of a mouse embryo embedded in solid paraffin and a formalin-fixed full-thickness sample of human left ventricle in water with a spatial resolution of 21.5 µm.


Matrine suppresses AGE-induced HAEC injury by inhibiting ROS-mediated NRLP3 inflammasome activation.
Diabetes is characterized by a high level of advanced glycation end products (AGEs), which induce damage in the arterial endothelium. Matrine has been shown to have cardioprotective effects. This study's aim was to investigate the protective effects and possible molecular mechanisms of matrine in AGE-induced human aortic endothelial cell (HAEC) injury. Cultured HAECs were treated with AGEs and/or serially diluted matrine. Cell viability was evaluated by MTT assay. Intracellular reactive oxygen species production was determined by flow cytometry. The expression levels of nucleotide-binding, leucine-rich repeat, and pyrin-domain-containing 3 (NLRP3), adaptor molecule apoptosis-associated speck-like protein, cleaved caspase-1 and interleukin-1β (IL-1β) were assessed by Western blotting; the concentration of IL-1β in culture supernatants was determined by enzyme-linked immunosorbent assay (ELISA). In a concentration-dependent manner, matrine co-treatment with AGEs substantially inhibited the reduction in cell viability and the increase in intracellular reactive oxygen species induced by AGEs. Co-treatment with matrine significantly inhibited the AGE-induced increase in NLRP3, ASC, caspase-1, p20 and IL-1β expression in HAECs in a concentration-dependent manner. Moreover, the AGE-mediated increase in IL-1β expression in cell culture supernatants was also reduced by co-treatment with matrine in a concentration-dependent manner. AGEs induced HAEC injury by inducing reactive oxygen species -mediated NLRP3 inflammasome activation. Matrine recovered HAEC viability by inhibiting reactive oxygen species -mediated NLRP3 inflammasome activation.


The hepatitis B virus X protein promotes hepatocellular carcinoma metastasis by upregulation of matrix metalloproteinases.
The hepatitis B virus (HBV) is a major cause of human hepatocellular carcinoma (HCC) which has a very high mortality rate due to high incidence of metastasis. It is unknown whether HBV contributes to HCC metastasis. In this report, we present clinical data obtained from HCC patients indicating that the expression of hepatitis B virus X protein (HBx) in HCC is associated with an increased expression of membrane-type 1 matrix metalloproteinase (MT1-MMP), and matrix metalloproteinase-2(MMP-2), which correlates with a poor prognosis. We further demonstrate experimentally that HBx upregulates MT1-MMP, which in turn induces MMP-2. Significantly, HBx-mediated MMP activation is associated with a marked increase of cell migration, as revealed by both wound-healing and transwell migration assays, suggesting that HBx may facilitate tumor cell invasion by upregulation of MMPs and subsequent destruction of the extracellular matrix. Together, our results support a model in which HBx contributes to HCC metastasis by upregulation of MMPs.


Effects of exercise on depressive behavior and striatal levels of norepinephrine, serotonin and their metabolites in sleep-deprived mice.
Exercise is a promising adjunctive therapy for depressive behavior, sleep/wake abnormalities, cognition and motor dysfunction. Conversely, sleep deprivation impairs mood, cognition and functional performance. The objective of this study is to evaluate the effects of exercise on anxiety and depressive behavior and striatal levels of norepinephrine (NE), serotonin and its metabolites in mice submitted to 6h of total sleep deprivation (6h-TSD) and 72h of Rapid Eye Movement (REM) sleep deprivation (72h-REMSD). Experimental groups were: (1) mice submitted to 6h-TSD by gentle handling; (2) mice submitted to 72h-REMSD by the flower pot method; (3) exercise (treadmill for 8 weeks); (4) exercise followed by 6h-TSD; (5) exercise followed by 72h-REMSD; (6) control (home cage). Behavioral tests included the Elevated Plus Maze and tail-suspension. NE, serotonin and its metabolites were determined in the striatum using high-performance liquid chromatography (HPLC). Sleep deprivation increased depressive behavior (time of immobilization in the tail-suspension test) and previous exercise hindered it. Sleep deprivation increased striatal NE and previous exercise reduced it. Exercise only was associated with higher levels of serotonin. Furthermore, exercise reduced serotonin turnover associated with sleep deprivation. In brief, previous exercise prevented depressive behavior and reduced striatal high NE levels and serotonin turnover. The present findings confirm the effects of exercise on behavior and neurochemical alterations associated with sleep deprivation. These findings provide new avenues for understanding the mechanisms of exercise.


Adenomyosis among samples from hysterectomy due to abnormal uterine bleeding in Ahwaz, southern Iran.
Adenomyosis is one of the most common, yet underdiagnosed, underlying causes of abnormal uterine bleeding (AUB). We aimed to evaluate the prevalence of adenomyosis among subjects who underwent hysterectomy due to AUB. We studied the pathological specimens from 100 cases of AUB who underwent hysterectomy and were referred to Jundishapur University of Medical Sciences, Ahwaz (Iran) from 2007 to 2010. All specimens were reviewed by the same pathologist. Pathological findings included adenomyosis 21%, leiomyoma 30%, adenomyosis and leiomyoma 21%, adenomyosis and other pathological causes 7%, and other pathological causes 21%. The overall prevalence of adenomyosis was 49%. Mean age of the patients was 46.9 ± 7.8 years and the highest frequency of adenomyosis was observed in the age group 30-60 years. Overall prevalence of adenomyosis in the population with AUB (49%) that we studied was higher than that in the reports from other populations. Occurrence of isolated adenomyosis in those aged less than 30 years was rare, and adenomyosis was usually accompanied by other lesions.


Knowledge of medical students, residents, and attending physicians about opiate abuse.
A questionnaire concerning knowledge of opiate abuse and attitudes about abusers was administered to 94 randomly selected physicians and medical students at a large urban teaching hospital. Physicians from four clinical departments and at each level of residency training and medical students in the final year were represented. The mean knowledge score was 3.3 out of a possible 12. Neither the level of training nor specialty was related to test score for the group as a whole. However, family practitioners gained knowledge with increasing experience, while medical and surgical specialists scored lower as they advanced in training. On the attitude section, physicians had strong but individualistic views about drug abuse. Level of training, specialty, and knowledge test score were on the whole unrelated to attitude. The results indicated that physicians at every level of training might benefit from improved teaching in the area of opiate abuse.


Clonal anergy of memory B cells in epitope-specific regulation.
Immunization of carrier (keyhole limpet hemocyanin (KLH)) primed mice with the hapten-carrier TNP-KLH induces specific suppression for the IgG anti-TNP-response without interfering with the response to epitopes on the carrier molecule. To examine the status of hapten-specific memory B cells from suppressed mice, highly enriched populations of TNP-specific memory B cells were purified from the spleen of TNP-KLH (control) or KLH/TNP-KLH (suppressed) immunized mice and tested in vitro for their ability to respond to TD or TI (TNP-KLH, TNP-LPS) antigenic challenge in presence of a KLH-specific Th cell line. Similar numbers of TNP-specific B cells with the characteristics of memory B cells were obtained from control and suppressed mice. TNP-specific B cells from suppressed mice could be triggered to IgG production by TNP-LPS but had an impaired ability to differentiate into IgG-secreting cells in response to TNP-KLH. This impaired IgG response to TNP-KLH was not due to an active suppression by a subset of TNP-specific B cells, or to an impedence of memory cells to a class switching but to an intrinsic memory B cell defect. TNP-specific B cells from suppressed mice were as efficient as memory B cells from control mice to present TNP-KLH to KLH-specific Th cells and to proliferate in response to T cell help. Our data support the view that the effector mechanism of epitope specific regulation does not interfere with the development of hapten-specific memory B cells but that these cells have an intrinsic defect that prevents their differentiation into active IgG antibody secreting cells in response to a T-dependent antigenic challenge.


Cardamine hirsuta: a comparative view.
Current advances in developmental genetics are increasingly underpinned by comparative approaches as more powerful experimental tools become available in non-model organisms. Cardamine hirsuta is related to the model plant Arabidopsis thaliana and comparisons between these two experimentally tractable species have advanced our understanding of development and diversity. The power of forward genetics to uncover new biology was evident in the isolation of REDUCED COMPLEXITY, a gene which is present in C. hirsuta but lost in A. thaliana, and shapes crucifer leaf diversity. Transferring two Knotted1-like homeobox genes between C. hirsuta and A. thaliana revealed a constraint imposed by pleiotropy on the evolutionary potential of cis regulatory change to modify leaf shape. FLOWERING LOCUS C was identified as a heterochronic gene that underlies natural leaf shape variation in C. hirsuta.


Health-related quality of life of adults with upper respiratory tract infections.
To determine the impact that upper respiratory tract infections have on patients' physical, social, and emotional functioning, we measured the health-related quality of life (HRQL) of adults with upper respiratory tract infections. Acute care clinic from November 2001 to February 2002. Prospectively administered survey. To measure HRQL, we used the Acute Form of the Short Form-36, version 2 (SF-36). For all 8 SF-36 subscales, we used norm-based scoring, in which the general U.S. population has a mean of 50. Adults who had symptoms for fewer than 30 days completed the SF-36; and were diagnosed with nonspecific upper respiratory infection, viral syndrome, otitis media, sinusitis, nonstreptococcal pharyngitis, streptococcal pharyngitis, or acute bronchitis. The sample of 318 patients was 63% female, 81% white, and had a mean age of 35 years. The primary diagnoses were nonspecific upper respiratory infection (42%), acute bronchitis (16%), sinusitis (12%), viral syndrome (9%), nonstreptococcal pharyngitis (8%), otitis media (7%), and streptococcal pharyngitis (6%). Patients had a mean general health subscale score of 50.9, which is not significantly different from the mean population value of 50 (P =.09). However, there were significant decrements in the remaining 7 subscales of the SF-36: physical functioning (45.5), role-physical (38.5), bodily pain (42.6), vitality (40.8), social functioning (37.8), role-emotional (46.8), and mental health (46.8; P <.0001 for all 7 subscales compared with normative values). Results were similar for the subset of patients with no comorbid illnesses (P <.001 for the same 7 subscales) and patients diagnosed with nonspecific upper respiratory infection (P <.001 for the same 7 subscales). These decrements were similar in magnitude, but somewhat different in subscale pattern, to those of adults with chronic lung disease, osteoarthritis, and depression. Physicians should remember that adults who seek care for upper respiratory tract infections have measurable, significant decrements in HRQL. For researchers, HRQL is an attractive, potential measure of outcome in future trials of established and novel therapies for upper respiratory tract infections.


Persistence of elevated deamidated gliadin peptide antibodies on a gluten-free diet indicates nonresponsive coeliac disease.
Histologically nonresponsive coeliac disease (NRCD) is a potentially serious condition diagnosed during the follow-up of coeliac disease (CD) when patients have persistent villous atrophy despite following a gluten-free diet (GFD). As current assessments of recovery are limited to invasive and costly serial duodenal biopsies, we sought to identify antibody biomarkers for CD patients that do not respond to traditional therapy. Bacterial display peptide libraries were screened by flow cytometry to identify epitopes specifically recognised by antibodies from patients with NRCD, but not by antibodies from responsive CD patients. Deamidated gliadin was confirmed to be the antigen mimicked by library peptides using ELISA with sera from NRCD (n = 15) and responsive CD (n = 45) patients on a strict GFD for at least 1 year. The dominant consensus epitope sequence identified by unbiased library screening QPxx(A/P)FP(E/D) was highly similar to reported deamidated gliadin peptide (dGP) B-cell epitopes. Measurement of anti-dGP IgG titre by ELISA discriminated between NRCD and responsive CD patients with 87% sensitivity and 89% specificity. Importantly, dGP antibody titre correlated with the severity of mucosal damage indicating that IgG dGP titres may be useful to monitor small intestinal mucosal recovery on a GFD. The finding of increased levels of anti-dGP IgG antibodies in CD patients on strict GFDs effectively identifies patients with NRCD. Finally, anti-dGP IgG assays may be useful to monitor mucosal damage and histological improvement in CD patients on a strict GFD.


Zika infection and the development of neurological defects.
Starting with the outbreak in Brazil, Zika virus (ZIKV) infection has been correlated with severe syndromes such as congenital Zika syndrome and Guillain-Barré syndrome. Here, we review the status of Zika virus pathogenesis in the central nervous system (CNS). One of the main concerns about ZIKV exposure during pregnancy is abnormal brain development, which results in microcephaly in newborns. Recent advances in in vitro research show that ZIKV can infect and obliterate cells from the CNS, such as progenitors, neurons, and glial cells. Neural progenitor cells seem to be the main target of the virus, with infection leading to less cell migration, neurogenesis impairment, cell death and, consequently, microcephaly in newborns. The downsizing of the brain can be directly associated with defective development of the cortical layer. In addition, in vivo investigations in mice reveal that ZIKV can cross the placenta and migrate to fetuses, but with a significant neurotropism, which results in brain damage for the pups. Another finding shows that hydrocephaly is an additional consequence of ZIKV infection, being detected during embryonic and fetal development in mouse, as well as after birth in humans. In spite of the advances in ZIKV research in the last year, the mechanisms underlying ZIKV infection in the CNS require further investigation particularly as there are currently no treatments or vaccines against ZIKV infection.


A Service-Constrained Positioning Strategy for an Autonomous Fleet of Airborne Base Stations.
This paper proposes a positioning strategy for a fleet of unmanned aerial vehicles (UAVs) airlifting wireless base stations driven by communication constraints. First, two schedulers that model the distribution of resources among users within a single cell are analyzed. Then, an UAV autonomous positioning strategy is developed, based on a fair distribution of the radio resources among all the users of all the cells in a given scenario, in such a way that the user bitrate is the same regardless the users' distribution and spatial density. Moreover, two realistic constraints are added related to capacity of the backhaul link among the UAVs and the ground station: the bitrate delivered per UAV and the total backhaul bandwidth shared among all the UAVs. Additionally, an energy consumption model is considered to evaluate the efficiency and viability of the proposed strategy. Finally, numerical results in different scenarios are provided to assess both the schedulers performance and the proposed coordinated positioning strategy for the UAVs.


Patient Outcomes after Fat Grafting to the Radiated Chest Wall before Delayed Two-stage Alloplastic Breast Reconstruction.
Two-stage alloplastic breast reconstruction in patients having received mastectomy and radiation is associated with a high rate of complications. Fat grafting has been shown to mitigate the effects of radiation on the chest wall to allow for alloplastic reconstruction. In this study, we assess the outcomes (after a mean follow-up of 28 months), including complications and revisional procedures, of women who had fat grafting to the radiated chest wall before two-stage implant-based breast reconstruction. A retrospective chart review was performed on consecutive patients seeking delayed implant-based reconstruction after simple mastectomy and postmastectomy radiation therapy between 2011 and 2015. All patients underwent two sessions of fat grafting to the radiated chest wall before inserting a tissue expander and subsequent exchange to a silicone implant. Twenty patients were included in the study. No reconstructive failures were recorded. The short-term complication rate was 5%, with one hematoma leading to a revisional procedure. The mean follow-up after reconstruction was 28 months. During follow-up, two patients (10%) developed capsular contracture grade IV with implant malposition, leading to capsular revision and implant exchange. Four patients (20%) underwent additional fat grafting for contour deformities. Fat grafting before two-stage alloplastic breast reconstruction in patients treated with mastectomy and postmastectomy radiation therapy may provide an alternate method of alloplastic reconstruction in a select group of patients who are not suitable for autogenous reconstruction. Follow-up data show that additional surgery may be required for correction of implant malposition and capsular contracture.


CORRELATION OF PAIRWISE GENETIC AND GEOGRAPHIC DISTANCE MEASURES: INFERRING THE RELATIVE INFLUENCES OF GENE FLOW AND DRIFT ON THE DISTRIBUTION OF GENETIC VARIABILITY.
Attempts to relate estimates of regional FST to gene flow and drift via Wright's (1931) equation FST ≈ 1/ (4Nm + 1) are often inappropriate because most natural sets of populations probably are not at equilibrium (McCauley 1993), as assumed by the island model upon which the equation is based, or ineffective because the influences of gene flow and drift are confounded in the product Nm. Evaluations of the association between genetic (FST ) and geographic distances separating all pairwise populations combinations in a region allows one to test for regional equilibrium, to evaluate the relative influences of gene flow and drift on population structure both within and between regions, and to visualize the behavior of the association across all degrees of geographic separation. Tests of the model using microsatellite data from 51 populations of eastern collared lizards (Crotaphytus collaris collaris) collected from four distinct geographical regions gave results highly consistent with predicted patterns of association based on regional differences in various historical and ecological factors that affect the amount of drift and gene flow. The model provides a prerequisite for and an alternative to regional FST analyses, which often simply assume regional equilibrium, thus potentially leading to erroneous and misleading inferences regarding regional population structure.


Microbial Metalloproteomics.
Metalloproteomics is a rapidly developing field of science that involves the comprehensive analysis of all metal-containing or metal-binding proteins in a biological sample. The purpose of this review is to offer a comprehensive overview of the research involving approaches that can be categorized as inductively coupled plasma (ICP)-MS based methods, X-ray absorption/fluorescence, radionuclide based methods and bioinformatics. Important discoveries in microbial proteomics will be reviewed, as well as the outlook to new emerging approaches and research areas.


[Decontamination of organophosphorus compounds: Towards new alternatives].
Organophosphorus coumpounds (OP) are toxic chemicals mainly used for agricultural purpose such as insecticides and were also developed and used as warfare nerve agents. OP are inhibitors of acetylcholinesterase, a key enzyme involved in the regulation of the central nervous system. Chemical, physical and biological approaches have been considered to decontaminate OP. This review summarizes the current and emerging strategies that are investigated to tackle this issue with a special emphasis on enzymatic remediation methods. During the last decade, many studies have been dedicated to the development of biocatalysts for OP removal. Among these, recent reports have pointed out the promising enzyme SsoPox isolated from the archaea Sulfolobus solfataricus. Considering both its intrinsic stability and activity, this hyperthermostable enzyme is highly appealing for the decontamination of OP.


Pinocembrin triggers Bax-dependent mitochondrial apoptosis in colon cancer cells.
Bioflavanoids are the major pigments in plants with multitude of biological activities including inhibition of proliferation or induction of apoptosis in tumor cells. Even though the safety records of most flavanoids are exceptional, its therapeutic use is still in its infancy. We have isolated pinocembrin (5,7-dihydroxyflavanone) from Alpinia galanga that showed cytotoxicity against a variety of cancer cells including normal lung fibroblasts with relative nontoxicity to human umbilical cord endothelial cells. The compound induced loss of mitochondrial membrane potential with subsequent release of cytochrome c and processing of caspase-9 and -3 in colon cancer cell line HCT 116. Processing of caspase-8 was minimal. The initial trigger for mitochondrial apoptosis appears to be by the translocation of cytosolic Bax protein to mitochondria. Overexpression of proapoptotic Bax protein sensitized the colon cancer cells to pinocembrin-induced apoptosis and Bax knockout cells were resistant to pinocembrin-induced apoptosis. Antiapoptotic protein Bcl-X(L) only partially prevented apoptosis induced by this compound. The Bax-dependent cell death involving classical cytochrome c release and processing of caspase-9 and -3 suggests that pinocembrin is a classical mitochondrial apoptosis inducer. But the failure of Bcl-X(L) overexpression to completely prevent apoptosis induced by this compound suggests that pinocembrin is capable of triggering mitochondrial-independent cell death that needs to be clarified. The existence of cell death upon Bcl-X(L) overexpression is a promising feature of this compound that can be exploited against drug resistant forms of cancer cells either alone or in combination with other drugs.


Operative treatment for otosclerosis. Comparative study of long-term results following substitution of stapes by free cartilage grafts.
This comparative study of long-term results following the substitution of stapes by free cartilage grafts is based on 500 stapedectomies. The patients were operated on by the same surgeon (first author) and followed-up for a period of 5-20 years. Postoperative results, compared with the results of other stapedectomy techniques, demonstrate a statistically significant difference in favour of the cartilage implant technique with respect to the overall functional success rate and the incidence of postoperative complications.


Observation of an Unusual Uranyl Cation-Cation Interaction in the Strongly Fluorescent Layered Uranyl Phosphates Rb6[(UO2)7O4(PO4)4] and Cs6[(UO2)7O4(PO4)4].
Single crystals of two new uranyl phosphates, A6[(UO2)7O4(PO4)4] (A = Cs, Rb), featuring cation-cation interactions (CCIs) rarely observed in uranium(VI) compounds were synthesized by molten flux methods. This structure crystallizes in the triclinic space group P1̅ with lattice parameters, a = 9.2092(4) Å, b = 9.8405(4) Å, c = 10.1856(5) Å, α = 92.876(2)°, β = 95.675(2)°, and γ = 93.139(2)° for A = Cs and a = 9.2166(9) Å, b = 9.3771(10) Å, c = 10.1210(11) Å, α = 89.981(4)°, β = 96.136(4)°, and γ = 92.790(4)° for A = Rb. The optical properties are reported for both compounds and compared to a layered uranyl phosphate, K4[(UO2)3O2(PO4)2], having a similar phosphuranylite-based structure but no CCIs. Partial ion exchange of Cs and Rb cations into the Rb6[(UO2)7O4(PO4)4] and Cs6[(UO2)7O4(PO4)4] structures, respectively, was achieved.


Psychosocial Intervention on the Dual-Process Model for a Group of COVID-19 Bereaved Individuals in Wuhan: A Pilot Study.
Wuhan was the first large city where the initial breakout of COVID-19 took numerous lives. A group of social workers and mental health specialists coordinated the "Be Together Program" (BTP), a psychosocial grief intervention program to help a group of Wuhan COVID-19 bereaved people. Under the Dual-process model framework, BTP used the internet and social media as the main tools, combined with group and individual intervention. Additionally, it employed a "Supermarket Mode" with abundant intervention themes and approaches for BTP participants to choose according to their special needs. Additionally, Chinese cultural elements are integrated into the program. At the end of the program, the grief scores of participants in the qualified sample reduced significantly, and the prevalence of the potential Prolonged Grief Disorder diagnosis reduced from 75% to 12%. The study also found that the BTP was especially effective for those who had high levels of grief reaction.


Augmenting mesenchymal stem cell therapy for osteoarthritis via inflammatory priming: a comparative study on mesenchymal stem cells derived from various perinatal tissue sources.
Background: Osteoarthritis (OA), a degenerative disease prevalent among the elderly, poses significant challenges due to its high incidence and disability rates. Regrettably, there exists a lack of effective regenerative therapies for the irreversible degradation of cartilage in OA. Mesenchymal stem cells (MSCs), known for their robust differentiation and immune regulatory capabilities, have emerged as promising candidates for OA treatment. MSCs sourced from perinatal tissues offer the dual advantage of convenience in extraction and ethical non-controversy. However, the heterogeneous nature of MSCs derived from different perinatal tissue sources gives rise to varying therapeutic indications. Moreover, the immune response of MSCs may be modulated under the influence of inflammatory factors. Methods: In this study, we isolated mesenchymal stem cells from distinct parts of human perinatal tissue: umbilical cord-derived MSCs (UC-MSCs), fetal placenta-derived MSCs (FP-MSCs), and umbilical cord placental junction-derived MSCs (CPJ-MSCs). These cells were cultured in vitro and subjected to a 24-hour treatment with the inflammatory mediator Interleukin-1β (IL-1β). Subsequently, the MSCs were evaluated for changes in proliferation, migration, and regulatory capabilities. To assess the comparative anti-injury potential of MSCs from different sources, primary articular chondrocytes (ACs) were exposed to H2O2-induced injury and co-cultured with IL-1β-primed MSCs. Changes in the proliferation, migration, and regulatory abilities of ACs resembling those observed in OA were examined. Results: Following IL-1β treatment, all three types of MSCs displayed decreased rates of proliferation and migration. Notably, their chondrogenic differentiation capacities exhibited an enhancement. Additionally, diverse MSCs exhibited a degree of efficacy in restoring damaged ACs in vitro. Among these, CPJ-MSCs demonstrated superior potential in promoting cartilage cell proliferation, while FP-MSCs displayed notable anti-inflammatory effects. Conclusion: Our findings underscore the substantial capacity of primed FP-MSCs and CPJ-MSCs to alleviate the injury in OA-like ACs. Consequently, this study advocates for the prospective use of preconditioning strategies involving FP-MSCs and CPJ-MSCs in forthcoming OA therapies.


Specificity of Adaptive Immune Responses in Central Nervous System Health, Aging and Diseases.
The field of neuroimmunology endorses the involvement of the adaptive immune system in central nervous system (CNS) health, disease, and aging. While immune cell trafficking into the CNS is highly regulated, small numbers of antigen-experienced lymphocytes can still enter the cerebrospinal fluid (CSF)-filled compartments for regular immune surveillance under homeostatic conditions. Meningeal lymphatics facilitate drainage of brain-derived antigens from the CSF to deep cervical lymph nodes to prime potential adaptive immune responses. During aging and CNS disorders, brain barriers and meningeal lymphatic functions are impaired, and immune cell trafficking and antigen efflux are altered. In this context, alterations in the immune cell repertoire of blood and CSF and T and B cells primed against CNS-derived autoantigens have been observed in various CNS disorders. However, for many diseases, a causal relationship between observed immune responses and neuropathological findings is lacking. Here, we review recent discoveries about the association between the adaptive immune system and CNS disorders such as autoimmune neuroinflammatory and neurodegenerative diseases. We focus on the current challenges in identifying specific T cell epitopes in CNS diseases and discuss the potential implications for future diagnostic and treatment options.


Formation of the transverse nerve in moth embryos. I. A scaffold of nonneuronal cells prefigures the nerve.
We have studied the embryonic development of the transverse nerve (TN), an unpaired segmental nerve of the moth Manduca sexta. Two identified motor neurons and 16 identified neuroendocrine neurons project axons within the larval TN; therefore, the TN is both a peripheral nerve and a neurohaemal organ. At 33% of embryogenesis, and prior to the arrival of any neuronal growth cones, the position, shape, and trajectory of the TN are anticipated by two groups of nonneuronal cells that we call the strap and the bridge. At this time the strap and the bridge together consist of approximately 100 cells, all of which express a cell surface epitope recognized by the monoclonal antibody TN-1. As development proceeds, both the number of nonneuronal cells within the strap and the bridge and the fraction that expresses the TN-1 antigen(s) decrease. Moreover, individual cells within the strap become morphologically identifiable before the arrival of the neuronal growth cones. Most of the axons that project to the TN also express the TN-1 antigen(s) during their period of outgrowth. The two motor neuron growth cones are the first to reach the environment of the strap and the bridge, doing so at approximately 37%; having encountered these cellular structures, the growth cones restrict their navigation to this preexisting scaffolding, until they reach their muscle target. The neuroendocrine growth cones arrive later and also grow within the confines of the strap and the bridge (J.N. Carr and P.H. Taghert, 1988, Dev. Biol, 130, 500-512). In this first paper we describe the development of the strap and the bridge, and the interactions of the motor neuron growth cones with these structures. The observations are novel in documenting the extent and precision to which a peripheral nerve pathway is prefigured by a contiguous assemblage of nonneuronal cells.


Comparison of supine and prone positions for percutaneous nephrolithotomy in treatment of staghorn stones.
Percutaneous nephrolithotomy (PNL) is the primary treatment modality for management of staghorn stones. PNL in supine position has important advantages over prone positon. However, studies comparing prone and supine positions for PNL in staghorn stone patients have conflicting results, and the aim of the current study was to compare prone and supine positions for PNL in staghorn stone cases. Data of patients underwent PNL for staghorn stones in supine or prone position by a single urologist were collected prospectively. The supine and prone position groups were compared for stone free rate (SFR) and complication rates. All patients were evaluated with NCCT for evaluation of SFR. Chi-square test was used to compare categorical variables and Student t test was applied for continuous variables of the treatment groups. The groups were similar for demographic and stone-related characteristics. Multi-caliceal and intercostal access was more common in prone position. Operation duration was significantly shorter and hemoglobin drop was significantly less in supine group. SFR was 64.1 and 60.4% in the supine and prone groups, respectively (p = 0.72). Complication rates were similar in the two groups but Clavien III complications were observed in two patients in the prone group. PNL in supine position is an effective treatment for management of staghorn stones. The need for multi-caliceal and intercostal puncture is less when combined with retrograde intrarenal surgery. PNL in supine position should be considered as primary treatment option in staghorn stone cases.


Successful management following combined thoracic endovascular aortic repair and minimally invasive esophagectomy for primary aortoesophageal fistula: A case report.
Aortoesophageal fistula (AEF) is a rare but life-threatening pathology. We report a case of a primary AEF that was successfully managed with temporary thoracic endovascular aortic repair (TEVAR) and esophagectomy with video-assisted thoracoscopic surgery. A 73-year-old man was transferred to the emergency department with a complaint of hematemesis. A computed tomography scan identified an AEF due to aortic aneurysm. We placed a stent using TEVAR for the purpose of hemodynamic stasis, and the operation was performed 23 h after admission. Right video-assisted thoracoscopic esophagectomy (VATS-E) was chosen, and a cervical esophagostomy and a feeding gastrostomy tube was constructed. Infection had been effectively controlled postoperatively. Four months after the first operation, we performed esophageal reconstruction. At the 70-month follow-up examination, the patient had no signs of mediastinitis. VATS-E immediately after hemostabilization by TEVAR is useful management for primary AEF.


Kiwifruit's Allergy in Children: What Do We Know?
Kiwifruit allergy is an emerging pathological condition in both general and pediatric populations with a wide range of symptoms linked to variable molecular patterns, justifying systemic and cross-reactions with other allergens (i.e., latex, pollen, and fruit). Skin prick test (SPT), specific serum IgE (Act d 1, Act d 2, Act d 5, Act d 8, and Act d 10) directed against five out of thirteen molecular allergens described in the literature, and oral test challenge with kiwifruit are available for defining diagnosis. The management is similar to that of other food allergies, mostly based on an elimination diet. Although kiwi allergy has been on the rise in recent years, few studies have evaluated the clinical characteristics and methods of investigating this form of allergy. Data collected so far show severe allergic reaction to be more frequent in children compared to adults. Therefore, the aim of this review is to collect the reported clinical features and the available association with specific molecular patterns of recognition to better understand how to manage these patients and improve daily clinical practice.


[Management of complications after liver resection].
Hepatic resections represent a standard procedure for both benign and malignant liver diseases. Nevertheless, typical complications arise follow-ing hepatic surgery. Besides common problems, such as bile leakage or impaired wound healing, rare complications, like progressive liver failure or portal vein thrombosis are observed. Mortality and morbidity after liver resection depend on the preoperative constitution of the patient, on the state of the liver parenchyma and on the re-main-ing liver volume. In particular, a marked steatosis increases both morbidity and mortality of hepatic resections. The advances of modern chemotherapy increases the number of surgical patients, who were previously not resectable. However, the chemotherapy induced hepatotoxicity implies additional problems, thus increasing the morbidity of liver resections. Therefore, before planning hepatic surgery, the individual situation of the patient has to be evaluated in order to maximise the security of the operative procedure.


Acanthosis nigricans as a clinical marker of insulin resistance among overweight adolescents.
Acanthosis nigricans (AN) is a hyperpigmented dermatosis associated with obesity and insulin resistance (IR). There is no consensus whether AN extension scoring offers added value to the clinical estimation of IR. In this study we aimed to assess and score AN using both a short and an extended version of the scale proposed by Burke et al. and analyze the relationships of both versions with hyperinsulinemia and IR. We analyzed data from 139 overweight adolescents (body mass index ≥85th percentile) aged 12-18 with (n=67) or without (n=72) AN who were followed at a pediatric obesity clinic. Adolescents with AN had higher levels of insulin (d=0.56, P=0.003) and HOMA-IR (d=0.55, P=0.003) compared to those without. Neither the short nor the extended versions of AN scores explained either hyperinsulinemia (β=1.10, P=0.316; β=1.15, P=0.251) or IR (β=1.07, P=0.422; β=1.10, P=0.374). The presence of AN alone predicted hyperinsulinemia and the presence of IR in 7.3% (β=2.68, P=0.008) and 7.1% (β=2.59, P=0.009) of adolescents, respectively. Screening for AN at the neck and axilla is a noninvasive and cost-effective way to identify asymptomatic overweight adolescents with or at risk of developing IR.


Royal Australian and New Zealand College of Psychiatrists expert consensus statement for the treatment, management and monitoring of the physical health of people with an enduring psychotic illness.
To use expert consensus to inform the development of policy and guidelines for the treatment, management and monitoring of the physical health of people with an enduring psychotic illness. The Delphi method was used. A systematic search of websites, books and journal articles was conducted to develop a 416-item survey containing strategies that health professionals should use to treat, manage and monitor the physical health of people with an enduring psychotic illness. Three panels of Australian experts (55 clinicians, 21 carers and 20 consumers) were recruited and independently rated the items over three rounds, with strategies reaching consensus on a priori-defined levels of importance written into the expert consensus statement. The participation rate for the clinicians across all three rounds was 65%, with consumers and carers only completing one round due to high endorsement rates. Finally, 386 strategies were endorsed as essential or important by one or all panels. The endorsed strategies provided information on engagement and collaborative partnerships; clinical governance; risk factors, morbidity and mortality in people with enduring psychotic illness; assessment, including initial and follow-up assessments; barriers to care; strategies to improve care of people with enduring psychotic illness; education and training; treatment recommendations; medication side effects; and the role of health professionals. The consensus statement is intended to be used by health professionals, people with an enduring psychotic illness and their families and carers. The next step needed is an implementation strategy by the Royal Australian and New Zealand College of Psychiatrists and other stakeholders.


Lack of association between the 3092 T-->C Clock gene polymorphism and cluster headache.
Recent studies suggested that genetic factors play a role in cluster headache (CH). However, the type and the number of genes involved in the disease are still unclear. We performed an association study in a cohort of Italian CH patients to evaluate whether a particular allele or genotype of the Clock gene would modify the occurrence and the clinical features of the disease. One hundred and seven CH patients, diagnosed according to the International Classification of Headache Disorders, 2nd Edition, (ICHD-II) criteria, and 210 healthy age, sex and ethnicity-matched controls were genotyped for the 3092 T-->C Clock gene polymorphism (also known as 3111 T-->C). Phenotype and allele frequencies were similarly distributed in CH patients and controls. The clinical features of the disease were not significantly influenced by different genotypes. In conclusion, our study suggests that the 3092 T-->C polymorphism of the Clock gene is unlikely to play an important role in cluster headache.