Gamma-patterned sensory stimulation reverses synaptic plasticity deficits in rat models of early Alzheimer's disease.
Non-invasive sensory stimulation in the range of the brain's gamma rhythm (30-100 Hz) is emerging as a new potential therapeutic strategy for the treatment of Alzheimer's disease (AD). Here, we investigated the effect of repeated combined exposure to 40 Hz synchronized sound and light stimuli on hippocampal long-term potentiation (LTP) in vivo in three rat models of early AD. We employed a very complete model of AD amyloidosis, amyloid precursor protein (APP)-overexpressing transgenic McGill-R-Thy1-APP rats at an early pre-plaque stage, systemic treatment of transgenic APP rats with corticosterone modelling certain environmental AD risk factors and, importantly, intracerebral injection of highly disease-relevant AD patient-derived synaptotoxic beta-amyloid and tau in wild-type animals. We found that daily treatment with 40 Hz sensory stimulation for 2 weeks fully abrogated the inhibition of LTP in all three models. Moreover, there was a negative correlation between the magnitude of LTP and the level of active caspase-1 in the hippocampus of transgenic APP animals, which suggests that the beneficial effect of 40 Hz stimulation was dependent on modulation of pro-inflammatory mechanisms. Our findings support ongoing clinical trials of gamma-patterned sensory stimulation in early AD.


A novel frameshift mutation of Chediak-Higashi syndrome and treatment in the accelerated phase.
Chediak-Higashi syndrome (CHS) is a rare autosomal recessive immunodeficiency disease characterized by frequent infections, hypopigmentation, progressive neurologic deterioration and hemophagocytic lymphohistiocytosis (HLH), known as the accelerated phase. There is little experience in the accelerated phase of CHS treatment worldwide. Here, we present a case of a 9-month-old boy with continuous high fever, hypopigmentation of the skin, enlarged lymph nodes, hepatosplenomegaly and lung infection. He was diagnosed with CHS by gene sequencing, and had entered the accelerated phase. After 8 weeks of therapy, the boy had remission and was prepared for allogenic stem cell transplantation.


Putative mechanisms mediating tolerance for audiovisual stimulus onset asynchrony.
Audiovisual (AV) speech perception is robust to temporal asynchronies between visual and auditory stimuli. We investigated the neural mechanisms that facilitate tolerance for audiovisual stimulus onset asynchrony (AVOA) with EEG. Individuals were presented with AV words that were asynchronous in onsets of voice and mouth movement and judged whether they were synchronous or not. Behaviorally, individuals tolerated (perceived as synchronous) longer AVOAs when mouth movement preceded the speech (V-A) stimuli than when the speech preceded mouth movement (A-V). Neurophysiologically, the P1-N1-P2 auditory evoked potentials (AEPs), time-locked to sound onsets and known to arise in and surrounding the primary auditory cortex (PAC), were smaller for the in-sync than the out-of-sync percepts. Spectral power of oscillatory activity in the beta band (14-30 Hz) following the AEPs was larger during the in-sync than out-of-sync perception for both A-V and V-A conditions. However, alpha power (8-14 Hz), also following AEPs, was larger for the in-sync than out-of-sync percepts only in the V-A condition. These results demonstrate that AVOA tolerance is enhanced by inhibiting low-level auditory activity (e.g., AEPs representing generators in and surrounding PAC) that code for acoustic onsets. By reducing sensitivity to acoustic onsets, visual-to-auditory onset mapping is weakened, allowing for greater AVOA tolerance. In contrast, beta and alpha results suggest the involvement of higher-level neural processes that may code for language cues (phonetic, lexical), selective attention, and binding of AV percepts, allowing for wider neural windows of temporal integration, i.e., greater AVOA tolerance.


In Vivo Bioluminescence Imaging for Longitudinal Monitoring of Inflammation in Animal Models of Uveitis.
We develop a quantitative bioluminescence assay for in vivo longitudinal monitoring of inflammation in animal models of uveitis. Three models of experimental uveitis were induced in C57BL/6 albino mice: primed mycobacterial uveitis (PMU), endotoxin-induced uveitis (EIU), and experimental autoimmune uveitis (EAU). Intraperitoneal injection of luminol sodium salt, which emits light when oxidized, provided the bioluminescence substrate. Bioluminescence images were captured by a PerkinElmer In Vivo Imaging System (IVIS) Spectrum and total bioluminescence was analyzed using Living Image software. Bioluminescence on day zero was compared to bioluminescence on the day of peak inflammation for each model. Longitudinal bioluminescence imaging was performed in EIU and EAU. In the presence of luminol, intraocular inflammation generates detectable bioluminescence in three mouse models of uveitis. Peak bioluminescence in inflamed PMU eyes (1.46 × 105 photons/second [p/s]) was significantly increased over baseline (1.47 × 104 p/s, P = 0.01). Peak bioluminescence in inflamed EIU eyes (3.18 × 104 p/s) also was significantly increased over baseline (1.09 × 104 p/s, P = 0.04), and returned to near baseline levels by 48 hours. In EAU, there was a nonsignificant increase in bioluminescence at peak inflammation. In vivo bioluminescence may be used as a noninvasive, quantitative measure of intraocular inflammation in animal models of uveitis. Primed mycobacterial uveitis and EIU are both acute models with robust anterior inflammation and demonstrated significant changes in bioluminescence corresponding with peak inflammation. Experimental autoimmune uveitis is a more indolent posterior uveitis and generated a more modest bioluminescent signal. In vivo imaging system bioluminescence is a nonlethal, quantifiable assay that can be used for monitoring inflammation in animal models of uveitis.


Effect of Trigger Sensitivity on Redistribution of Ventilation During Pressure Support Ventilation Detected by Electrical Impedance Tomography.
In supine position, pressure support ventilation causes a redistribution of ventilation towards the ventral regions of the lung. Theoretically, a less sensitive support trigger would cause the patient to breathe more actively, potentially attenuating the effect of positive pressure ventilation. To quantify the effect of trigger setting, we assessed redistribution of ventilation during pressure support ventilation (PSV) using electrical impedance tomography (EIT). With approval from the local ethics committee, six orthopedic patients were enrolled. All patients had general anesthesia with a laryngeal mask airway and a standardized anesthetic regimen (sufentanil, propofol and sevoflurane). Pressure support trigger settings varied between 2 and 15 L/minute and compared to unassisted spontaneous breathing. From EIT data, the center of ventilation (COV), the fraction of the total ventilation per region of interest (ROI) and intratidal gas distribution were calculated. At all trigger settings, pressure support ventilation caused a significant ventral shift of the center of ventilation compared with during spontaneous breathing, confirmed by the analysis by regions of interest. During spontaneous breathing, COV was not different from baseline values obtained before induction of anesthesia. During PSV, the intratidal regional gas distribution (ITV-analysis) revealed subtle changes during the early inspiratory phase not detected by the COV-analysis. Pressure support ventilation, but not spontaneous breathing, induces a significant redistribution of ventilation towards the ventral region. The sensitivity of the support trigger appears to influence the distribution of ventilation only during the early phase of inspiration.


Vagus Nerve Stimulation for Tumor-Related Epilepsy: Does It Make Sense?
Seizure is a common presenting symptom for those with brain tumor due to its unique pathogenesis. Several choices of antiepileptic drug are available to use, but some patients can still go on to develop tumor-related refractory epilepsy. Vagus nerve stimulation is becoming a popular option for those with medical refractory epilepsy but no brain tumor due to its effectiveness. There are very few studies available that address the topic of using vagus nerve stimulation for tumor-related epilepsy. Here we discuss the evidence of using vagus nerve stimulation for refractory tumor-related epilepsy and its challenges and gaps moving forward.


Human gonadotropin therapy: hormonal and ultrasonographic characteristics of conceptual and nonconceptual cycles in the same women.
A retrospective analysis was carried out to assess hormonal and sonographic characteristics of 52 conceptual (P-cycles) and 53 nonconceptual (F-cycles) gonadotropin treatment cycles in the same women. In the P-cycles, an exponential E2 pattern was observed up to the day of hCG (human chorionic gonadotropin) administration (day 0). In the F-cycle group, a similar pattern was observed till day (-1), and then levels plateaued. Forty-two (80.9%) of the pregnancies were achieved when the active phase was 6 +/- 1 days; seven pregnancies (14.8%) occurred when the active phase was more than 7 days. Only one of these pregnancies was a singleton viable pregnancy (P less than .05). It is, therefore, postulated that 6 +/- 1 days rising E2 and exponential E2 rise pattern up to the day of hCG are the two main monitoring variables leading to the highest percentage of viable singleton or twin pregnancies in hMG-stimulated cycles.


Use of acute phase proteins in pleural effusion discrimination.
The differentiation between exudates and transudates is fundamental when investigating the cause of pleural effusions. Acute-phase proteins could be potentially useful markers in this discrimination. In the attempt to define diagnostic criteria for the differentiation of pleural exudates from transudates, we measured alpha 1 acid glycoprotein, C-reactive protein, haptoglobin, ceruloplasmin and transferrin in pleural effusions and serum in patients with pleural effusions of various etiologoies. We measured the concentrations of the above proteins in the serum and pleural fluid of 80 (54 exudate, 26 transudate) consecutive patients by immunoturbidometrical methods. Pleural effusion acute phase proteins were elevated in the patients with exudate compared to patients with transudate (p< 0.001 for all). In receiver operator characteristic analysis showed that pleural fluid ceruloplasmin levels and the ratio pleural fluid/serum transferrin were superior to the others. Using the optimum cut-off point of 0.16 g/L pleural fluid ceruloplasmin achieves a sensitivity of 92% with a specificity of 85%. In addition to, the optimum cut-off point for pleural fluid/serum transferrin ratio was 0.4 with sensitivity and specificity of 92% and 80%. When using together these parameters sensitivity and specificity were increased (95%, 85%). In differential diagnosis, none of these proteins were significantly different in subgroups of pleural exudate. We conclude that when using together ceruloplasmin levels in pleural fluid and the ratio of pleural to serum transferrin have a high sensitivity and specificity in discrimination of exudative pleural effusions.


Which patients should be offered caesarean section?
Caesarean section (CS) rates have steadily risen from 10% of all deliveries in the 1980s to a current figure of around 23.8%. Approximately 75% of CS are emergency procedures and only 25% are elective planned deliveries. When deciding whether to offer CS, it is important to consider the psychological implications for the patient as well as the physical and mental sequelae in future pregnancies. Clinicians should provide pregnant women with evidence-based information and support. Information should include details about the true indication(s) for the CS and what it implies, including its risks and benefits. The updated NICE guideline does not advocate CS in uncomplicated pregnancies. However, it supports CS on maternal request when attempts to empower the mother to have a vaginal birth have not been successful. CS on maternal request only represented 1.4% of all CS in 2001. CS may reduce perineal and abdominal pain during birth and 3 days postpartum. It may also reduce injury to the vagina, early postpartum haemorrhage and obstetric shock. The following patients should be offered a planned elective CS: singleton breech presentation at term, after external cephalic version has failed, has been declined or is contraindicated; multiple pregnancies when the first twin is not cephalic; placenta praevia, minor or major, (close to or covering the os); HIV-positive women who are not on any antiretroviral therapy, have a high viral load or co-infection with hepatitis C irrespective of viral load; and women with primary genital herpes simplex virus infection occurring in the third trimester.


Some considerations concerning the deep femoral artery.
The great importance of the deep femoral artery as a collateral vessel in occlusion of the superficial femoral artery is a well-established fact. It has been found in the course of reconstructive operations of this artery that the origin of the two circumflex arteries varies considerably. A study of one hundred cadavers has given some idea of the frequency and nature of these anatomical variations. The importance of this vessel as a collateral is partially explained by the fact that the deep femoral artery has two groups of branches, both of them anastomosing with the branches of the popliteal artery. If the deep femoral artery is to function adequately as a collateral, it has to have a large caliber. An explanation for this may be found in comparative anatomy. In the phylogenetically farther advanced vertebrate animals, all of which have very strongly developed extensors in the posterior extremities, the deep femoral artery which supplies blood to this muscle group is a branch of the iliac artery, and accordingly, a pelvic artery. In man, this artery originates distal to the inguinal ligament from the common femoral artery and supplies blood to less well-developed muscle groups. In this way, phylogeny explains the large caliber of the deep femoral artery, which has originally been a pelvic artery and it also explains the numerous anatomical variations at the site of the bifurcation of the common femoral artery.


Extrinsic allergic bronchiolitis in a bird fancier.
A patient in whom a severe systemic illness was characterised by weight loss, arthralgia and breathlessness was exposed to her pet bird. This pragmatic approach reproduced the features of her illness. The changes that occurred in her pulmonary physiology and histology differed from those seen in extrinsic allergic alveolitis in many important respects.


Pyeloduodenal fistula diagnosed with technetium-99m scintigraphy and managed with a conservative strategy.
We present a case of pyeloduodenal fistula in an 89-year-old woman with history of nephrolithiasis and recurrent urinary tract infection (UTI) who presented to the emergency department with back pain. CT revealed a malrotated right kidney with a large renal stone and possible fistulous connection between the second portion of the duodenum and the right renal collecting system. Technetium-99m scintigraphy confirmed presence of the fistula. The patient declined intervention and was discharged from the hospital with oral antibiotic suppressive therapy. The patient remained clinically stable at time of follow-up 3 months later. Spontaneous pyeloduodenal fistula is an aetiology of recurrent upper or lower UTIs or persistent bacteriuria though uncommonly recognised. Diagnosis may be achieved using several modalities, including technetium-99m scintigraphy. Nephrectomy and primary fistula closure has traditionally been the treatment of choice for this condition; however, conservative management is an option for patients with intact renal function.


Concomitant lymphoplasmacytic lymphoma and plasma cell myeloma, a diagnostic challenge.
Lymphoplasmacytic lymphoma and plasma cell myeloma are two B cell lymphoproliferative neoplasms derived from mature B-lymphocytes in different differentiation stages. The coexistence of these two tumors in the same patient is exceedingly rare and can be difficult to diagnose. A 76-year-old male presented with a pathologic fracture after a fall. Radiography showed a lytic lesion in the pelvis. Serum immunofixation showed distinct IgM kappa and IgA kappa monoclonal protein bands. Bone marrow examination revealed aggregates of small, mature lymphoid cells with admixed plasma cells. Immunohistochemical studies and flow cytometric analysis showed the lymphoid cells were CD10-/CD5- kappa restricted monoclonal B cells. The plasma cells were monoclonal with kappa light chain restriction. The majority of plasma cells were positive for IgA and cyclin D1 with a few plasma cells positive for IgM. Additional studies showed the presence of both a positive MYD88 L265P mutation and a CCND1/IGH fusion. A diagnosis of concomitant lymphoplasmacytic lymphoma and plasma cell myeloma was rendered. Concomitant lymphoplasmacytic lymphoma and plasma cell myeloma can be rarely encountered and is diagnostic challenging. It is commonly associated with biclonal monoclonal proteins. This case demonstrates the importance of a comprehensive work-up in the diagnosis of this disease combination and highlights the diagnostic role of MYD88 mutation study.


Needle aspiration of calcific deposits versus shock wave therapy for conservative therapy resistant calcifying tendinitis of the shoulder: protocol of a randomized, controlled trial.
Calcific tendinitis of the shoulder (CT) is a common disorder with a large disease burden. The initial treatment is with conservative measures. However, when this fails the next step treatment remains unclear. Minimal invasive treatment modalities have emerged. Needle aspiration of the calcific deposits (NACD) and extracorporeal shock wave therapy (ESWT) have both shown good clinical results. Nonetheless, in the current orthopedic literature there are not any studies available that compare both the effectiveness and cost-effectiveness of those two treatment modalities. Therefore, our primary objective is to compare the effectiveness of NACD to ESWT. A secondary objective is to compare the cost-effectiveness of both treatment modalities and workability. Following a power calculation using the minimal clinical important difference of our primary outcome (Constant-Murley score, CMS) 140 patients will be included in the study. Enrolment is based upon strict inclusion/ exclusion criteria outlined in the Methods section. Participants will be randomized by computer in two groups (e.g. 70 patients will receive NACD and 70 patients will receive ESWT). The NACD treatment will consist of a sonographically guided removal of the calcific deposits and the ESWT treatment will be a focused ESWT. Both treatments will be conducted according to a standardized protocol, as part of care as usual in our hospital. The primary outcome will be the between group differences in functional outcome (measured with the CMS) between baseline and after 12 months follow-up. Secondary outcomes will be questionnaires regarding the clinical outcome (SST) and quality of life (EQ-5D-5L). Furthermore, NRS pain and cost related questionnaires (iPCQ and ProDisQ) will be collected during follow-up after two months, six months and at final follow-up after 12 months. This study will provide more insight regarding treatment for conservative therapy resistant calcific tendinitis of the shoulder by comparing NACD to focused ESWT, which will aid the physician and patient in determining the appropriate treatment plan. Dutch trial register: NTR7093 registered on 11 March 2018.


Sympathetic neural mechanisms in human hypertension.
This review discusses the role of the sympathetic nervous system in the pathogenesis and maintenance of human hypertension. Three points are emphasized: first, there are mechanisms by which the sympathetic nervous system can contribute to the long-term regulation of vascular resistance and arterial pressure in addition to the moment-to-moment regulation of arterial pressure; second, the microneurographic method for direct intraneural recording of sympathetic nerve activity in humans has provided mounting evidence for increased sympathetic neural activity in human essential and renovascular hypertension; and third, there are both peripheral reflex and humoral mechanisms that may contribute to sympathetic overactivity in human hypertension.


Induction of linalool as a pharmaceutical and medicinal metabolite via cell suspension culture of cumin (Cuminum cyminum L.).
Cumin is an important medicinal plant in Iran. Plant cell suspension culture is a method for the production of medicinal and secondary metabolites. The linalool is a plant secondary metabolite that has been recognized as a neuroprotective agent. The purpose of this study was to evaluate the effects of salicylic acid elicitor on induction of linalool in cell suspension culture of cumin. For this purpose, the cumin seeds were prepared, to obtain sterile seedling, were disinfected with sodium hypochlorite and alcohol, and were cultured on MS basal medium. This research was conducted in two separate experiments including callus induction and suspension cultures. Leaf explants were prepared from sterile seedlings and used to produce callus on MS medium supplemented with 1 mg/l NAA and 0.5 mg/l BAP. In order to establish suspension culture, the appropriate calli were transferred to liquid medium. Then cell cultures were treated with elicitors. The effects of elicitor on the production of linalool secondary metabolite and cell viability were assessed by GC-Mass and tetrazolium test respectively. For this purpose, the salicylic acid (at concentrations of 0, 1, 2, 4 and 8 mg/l) was used. The experimental design was a completely randomized design with five treatments and three replications. The results of cell culture and GC-Mass analysis showed that salicylic acid had significant effects on the linalool production (<0.01). At all concentrations of salicylic acid, viability of the cells in suspension culture experiments was lower than control. Increasing the elicitor concentrations lead to reduction in cell survival. In conclusion it is possible to produce linalool as a secondary metabolite and pharmaceutical agent in cell culture of cumin. It is necessary to determine the best combination of medium and elicitor.


Comparative studies of the bactericidal, morphological and post-antibiotic effects of arbekacin and vancomycin against methicillin-resistant Staphylococcus aureus.
Arbekacin, an aminoglycoside antibiotic, has antibacterial activity against both Gram-positive and Gram-negative bacteria and is stable in the presence of aminoglycoside-inactivating enzymes produced by methicillin-resistant Staphylococcus aureus (MRSA). In this report, the antibacterial activity of arbekacin was compared with that of vancomycin, a glycopeptide antibiotic that also has potent antibacterial activity against MRSA. Arbekacin showed concentration-dependent bactericidal activity against MRSA strain 1936 (0.5-2 x MIC), but vancomycin showed only slight bactericidal activity, even at high concentrations of 19 x MIC. Arbekacin showed a longer post-antibiotic effect (2.3-3.8 h) than vancomycin (0-1.3 h) against MRSA strain 1936. Arbekacin induced marked morphological changes at 0.5 x MIC and the changes remained for 2 h after removal of the agent. When exposed to 0.5 x MIC of vancomycin, no notable morphological change was observed in the treated cells. Since arbekacin has broad-spectrum activity, these findings suggest that it may be a useful agent against MRSA infection, especially for polymicrobial MRSA infection with Gram-negative bacilli, such as Pseudomonas aeruginosa.


Low virulence of oocysts of Czech Toxoplasma gondii isolates on the basis of biological and genetic characteristics.
The virulence of the oocysts of 7 Czech Toxoplasma gondii isolates was tested. The oocysts were obtained by experimental infection of cats with the tissue cysts of T. gondii isolates from dogs, cats, and rabbits. The cats shed the oocysts in feces, with prepatent periods of 3-5 days postinfection (PI); the patent period was 7-18 days. The number of oocysts shed varied between 0.94 million and 47 million, with 0.66 million-39 million oocysts found in the daily samples of excrement. The cats ceased oocyst production at 11-22 days PI. Sporulated oocysts were used to prepare infective doses of 1 to 10(5) oocysts for oral infection of 10 mice. Deoxyribonucleic acid isolated from 4 T. gondii isolates was used in polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for amplification of the ROP1 gene and restriction of the product of amplification by restriction endonuclease DdeI. On the basis of their biological characteristics, all 7 isolates belonged to the group of "avirulent" strains. In the PCR-RFLP tests, 2 isolates, K9 and K19, showed an "avirulent" strain pattern.


Virus and virus-like particles in the faeces of cats with and without diarrhoea.
Negative staining electron microscopy was used to identify viruses in 166 normal and 62 diarrhoeal faecal samples from 208 cats admitted to an animal shelter during a 16-month period (March 1984 to June 1985). On the basis of size and shape 7 distinct viral types were detected: 24 nm parvovirus-like particles, 30 nm astrovirus, 30 nm picornavirus-like particles, reovirus, rotavirus, coronavirus and a 75 nm "togavirus-like" particle. The incidence of these particles in the 208 cats was 11%, 7%, 6%, 0.4%, 5%, 1% and 1% respectively. Virus isolation studies using 40 of the faecal samples succeeded in isolating reovirus 1 in 2 cases. Immune electron microscope studies demonstrated the presence of antibody in a human serum to cat astrovirus, but failed to clarify the identity of the parvovirus-like particles and picornavirus-like particles, other than showing that some of the parvovirus-like particles were not related to feline panleukopenia virus. It was found that parvovirus-like particles, astrovirus, picornavirus-like particles, reovirus and rotavirus could be excreted by cats with normal faeces as well as cats with diarrhoeal faeces. Parvovirus-like particles, astrovirus, picornavirus-like particles and rotavirus could be excreted in high concentration in normal faeces. There was no simple relationship between age and diarrhoea in the population of cats studied. Age was not a critical factor in the excretion of parvovirus-like particles, astrovirus, picornavirus-like particles and rotavirus. The incidence of diarrhoea was not clearly associated with the seasons.


Structural, electrochemical, phosphate-hydrolysis, DNA binding and cleavage studies of new macrocyclic binuclear nickel(II) complexes.
New macrocyclic binuclear nickel(ii) complexes have been synthesized by using the bicompartmental mononuclear complex [NiL] [3,30-((1E,7E)-3,6-dioxa-2,7-diazaocta-1,7-diene-1,8-diyl)bis(3-formyl-5-methyl-2-diolato)nickel(II)] with various diamines like 1,2-bis(aminooxy)ethane (L(1)), 1,2-diamino ethane (L(2)), 1,3-diamino propane (L(3)), 1,4-diamino butane (L(4)), 1,2-diamino benzene (L(5)), and 1,8-diamino naphthalene (L(6)). The complexes were characterized by elemental analysis and spectroscopic methods. The molecular structures of the symmetrical binuclear complex [Ni(2)L(1)(H(2)O)(4)](ClO(4))(2) (1) and unsymmetrical binuclear complex [Ni(2)L(3)(H(2)O)(4)](ClO(4))(2).(H(2)O)(4) (3) were determined by single-crystal X-ray diffraction. The geometry around both the nickel(II) ions in each molecule is a slightly distorted octahedral. The distance between the Ni...Ni centers for complex 1 is 3.039 A and for complex 3 is 3.059 A. The influence of the coordination geometry and the ring size of the binucleating ligands on the electronic, redox, phosphate hydrolysis, DNA binding and cleavage properties have been studied. Electrochemical studies of the complexes show two quasi-reversible one electron reduction processes between -0.49 to -1.69 V. The reduction potential of the binuclear Ni(II) complexes shifts towards anodically upon increasing the macrocyclic ring size. The observed first order rate constant values for the hydrolysis of 4-nitrophenyl phosphate reaction are in the range from 8.69 x 10(-3) to 1.85 x 10(-2) s(-1). The complexes show good binding propensity to calf thymus DNA giving binding constant values in the range from 1.4 x 10(4) to 17.5 x 10(4) M(-1). The absorption, fluorescence and CD spectral data suggests that the complexes are strongly interacting with DNA. These complexes display hydrolytic cleavage of supercoiled pBR322DNA in the presence of H(2)O(2) at pH 7.2 and 37 degrees C. The hydrolytic cleavage of DNA by the complexes is supported by the evidence from free radical quenching and T4 ligase ligation. The pseudo-Michaelis-Menten kinetic parameters k(cat) = 1.27 +/- 0.4 h(-1) and K(M) = 7.7 x 10(-2) M for naphthalene diimine containing macrocyclic binuclear nickel(II) complex, (6) were obtained.


A Case of Neutrophil-Rich Anaplastic Large-Cell Lymphoma with Relapse.
After anaplastic large-cell lymphoma (ALCL) was first described by Stain in 1985, there have been several histological variants of ALCL reported. There are classified histological subtypes of ALCL, such as lymphohistiocytic, small cell, Hodgkin-like, composite pattern, and other less common variants including neutrophil-rich ALCL. A 63-year-old male patient presented with erythematous exophytic mass on the left lower leg. In the past, his condition had been diagnosed as abdominal primary cutaneous ALCL (pcALCL), which recurred as systemic ALCL (sALCL) in the left bronchus. After treatment, he achieved complete remission. Histopathologic examination showed large-sized pleomorphic, anaplastic mitotic tumor cells, several neutrophils, and a few lymphocytes. Neutrophil-rich ALCL is a rare histological variant of ALCL. It is characterized by the presence of CD30-positive anaplastic tumor cells with numerous neutrophil infiltrations. Neutrophil-rich ALCL responds well to treatment but tends to recur. There were four cases reported to have recurrent neutrophil-rich ALCL. All cases were diagnosed with neutrophil-rich pcALCL prior to recurrence. Three cases had local recurrence, and only one case relapsed as sALCL. Herein, we present the first case of neutrophil-rich ALCL recurring as sALCL twice.


The emerging role of immunotherapy in head and neck squamous cell carcinoma (HNSCC): anti-tumor immunity and clinical applications.
Head and neck squamous cell carcinoma (HNSCC) carries a poor prognosis, with low survival rates for advanced stage tumors and minimal improvement in survival trends through the past decades. It is becoming increasingly clear that HNSCC oncogenesis and evolution is characterized by profound immune defects, as cancer cells evade immunosurveillance due to accumulation of genetic mutations and tumor heterogeneity. Improved understanding of the role of the immune system in cancer has led to the identification of novel therapeutic targets, which are being investigated for their potential to provide durable responses. In this review, we will summarize the role of the immune system in HNSCC, the rationale behind immunotherapy strategies and their clinical applications.


Specific CaMKIIs mediate convergent extension cell movements in early zebrafish development.
Noncanonical Wnts are morphogens that can elevate intracellular Ca2+ , activate the Ca2+ /calmodulin-dependent protein kinase, CaMKII, and promote cell movements during vertebrate gastrulation. Zebrafish express seven CaMKII genes during embryogenesis; two of these, camk2b1 and camk2g1, are necessary for convergent extension (CE) cell movements. CaMKII morphant phenotypes were observed as early as epiboly. At the 1-3 somite stage, neuroectoderm and paraxial cells remained unconverged in both morphants. Later, somites lacked their stereotypical shape and were wider, more closely spaced, and body gap angles increased. At 24hpf, somite compression and notochord undulation coincided with a shorter and broader body axis. A camk2b1 crispant was generated which phenocopied the camk2b1 morphant. The levels of cell proliferation, apoptosis and paraxial and neuroectodermal markers were unchanged in morphants. Hyperactivation of CaMKII during gastrulation by transient pharmacological intervention (thapsigargin) also caused CE defects. Mosaically expressed dominant-negative CaMKII recapitulated these phenotypes and showed significant midline bifurcation. Finally, the introduction of CaMKII partially rescued Wnt11 morphant phenotypes. Overall, these data support a model whereby cyclically activated CaMKII encoded from two genes enables cell migration during the process of CE.


[Efficacy of Hybrid anterior cervical spine surgery on range of motion and curvature in the treatment of cervical degenerative diseases].
To observe the change of cervical curvature and range of motion (ROM) on imaging at 6 months after Hybrid surgery. A total of 29 patients with cervical degenerative disease who underwent Hybrid surgery from January 2017 to July 2018 were retrospectively analyzed. Also, they all met the inclusion criteria and had complete preoperative and 6 months postoperative imaging data. There were 11 males and 18 females, aged from 34 to 76 (55.86±10.69) years, and the operation time was from 2 to 4(3.03±0.51) hours. The Cobb angle method was used to measure the changes of cervical curvature and ROM of C2-C7, replacement segments, fusion segments, and upper adjacent segments on cervical lateral X-rays before and 6 months after surgery. There was no statistically significant difference in C2-C7 curvature and ROM between 6 months after operation and before operation (P>0.05). The degree of curvature and ROM of the replacement segment increased compared with that before operation (P<0.05). The curvatureof the fusion segment was increased than that before operation (P<0.05). There was no statistically significant difference in ROM of the fusion segment compared with that before operation (P>0.05). There was no statistically significant difference in the curvature and ROM of the upper adjacent segments compared with those before operation (P>0.05). There was no significant difference in the curvature between the replacement and fusion segments before and 6 months after operation (P>0.05);the ROM of the replacement segment was higher than that of the fusion segment at 6 months after operation (P<0.05). Hybrid surgery reconstructs the lordotic curvature of the entire cervical spine and the responsible segment, retains the ROM of the cervical replacement segment, and restores the biomechanical function of cervical spine.


Interpersonal schemata in child psychotherapy: a cognitive-interpersonal perspective.
Presents a cognitive-interpersonal framework for child psychotherapy derived from attachment theory. Interpersonal schema, conceptualized as expectations regarding others' probable responses to the self, are posited as a key mediating mechanism linking past interpersonal experience with current social-emotional functioning, and as an important target for intervention. Three schema-based models of pathogenic process are examined: preemptive information-processing, schema-triggered affect, and schema-primed interpersonal and emotion-regulation strategies. Implications for assessment of and intervention with interpersonal schema are considered. Preventive, compensatory, and remedial intervention strategies are proposed.


Professional continuous glucose monitoring in subjects with type 1 diabetes: retrospective hypoglycemia detection.
An important task in diabetes management is detection of hypoglycemia. Professional continuous glucose monitoring (CGM), which produces a glucose reading every 5 min, is a powerful tool for retrospective identification of unrecognized hypoglycemia. Unfortunately, CGM devices tend to be inaccurate, especially in the hypoglycemic range, which limits their applicability for hypoglycemia detection. The objective of this study was to develop an automated pattern recognition algorithm to detect hypoglycemic events in retrospective, professional CGM. Continuous glucose monitoring and plasma glucose (PG) readings were obtained from 17 data sets of 10 type 1 diabetes patients undergoing insulin-induced hypoglycemia. The CGM readings were automatically classified into a hypoglycemic group and a nonhypoglycemic group on the basis of different features from CGM readings and insulin injection. The classification was evaluated by comparing the automated classification with PG using sample-based and event-based sensitivity and specificity measures. With an event-based sensitivity of 100%, the algorithm produced only one false hypoglycemia detection. The sample-based sensitivity and specificity levels were 78% and 96%, respectively. The automated pattern recognition algorithm provides a new approach for detecting unrecognized hypoglycemic events in professional CGM data. The tool may assist physicians and diabetologists in conducting a more thorough evaluation of the diabetes patient's glycemic control and in initiating necessary measures for improving glycemic control.


Secreted dipeptidyl peptidases as potential virulence factors for Microsporum canis.
Dermatophytoses caused by Microsporum canis are frequently encountered in cats and dogs; they are highly contagious and readily transmissible to humans. In this study, two single genes, respectively coding for dipeptidyl peptidases IV and V (DppIV and DppV), were isolated and characterized. Both proteins share homology with serine proteases of the S9 family, some of which display properties compatible with implication in pathogenic processes. Both genes are expressed in vivo in experimentally infected guinea-pigs and in naturally infected cats, and when the fungus is grown on extracellular matrix proteins as the sole nitrogen and carbon source. DppIV and V were produced as active recombinant proteases in the yeast Pichia pastoris; the apparent molecular weight of rDppV is 83 kDa, whereas rDppIV appears as a doublet of 95 and 98 kDa. Like other members of its enzymatic subfamily, rDppIV has an unusual ability to cleave Pro-X bonds. This activity does not enhance the solubilization of keratin by fungal secreted endoproteases, and the protease probably acts solely on small soluble peptides. RDppV showed no ability to induce delayed-type hypersensitivity (DTH) skin reactions in guinea-pigs, despite the known immunogenic properties of homologous proteins.


The serotonin retaining effect of lithium in the rat thyroid.
The hypothesis of a lithium induced serotonin retention in the rat thyroid has been tested. It has been found that the thyroid in rats treated with lithium contains double the amount of serotonin compared with glands from untreated animals. The ability of TSH to stimulate serotonin release is inhibited by lithium. The ability of serotonin to stimulate thyroid hormone secretion in vitro is documented. The inhibitory action of lithium on both TSH and serotonin stimulation of hormone release is documented. The serotonin retaining effect of lithium as part of the goitrogenic effect of this ion is discussed.


Oral candidiasis in high-risk patients as the initial manifestation of the acquired immunodeficiency syndrome.
We studied the frequency with which unexplained oral candidiasis led to unequivocal acquired immunodeficiency syndrome (AIDS) in patients at risk. Twenty-two previously healthy adults with unexplained oral candidiasis, of whom the 19 tested had a reversed T4/T8 ratio and 20 had generalized lymphadenopathy, were compared with 20 similar patients with a reversed T4/T8 ratio and generalized lymphadenopathy who did not have oral candidiasis. All were intravenous-drug abusers, homosexual or bisexual men, or both. Thirteen of the 22 patients with oral candidiasis (59 per cent) acquired a major opportunistic infection or Kaposi's sarcoma at a median of three months (range, 1 to 23) as compared with none of 20 patients with generalized lymphadenopathy and immunodeficiency but without candidiasis who were followed for a median of 12 months (range, 5 to 21) (P less than 0.001). AIDS developed in 12 of 15 patients with candidiasis and T4/T8 ratios less than or equal to 0.51, as compared with none of four with ratios equal to or greater than 0.60 (P less than 0.01). We conclude that in patients at high risk for AIDS, the presence of unexplained oral candidiasis predicts the development of serious opportunistic infections more than 50 per cent of the time. Whether the remainder will have AIDS is not yet known.


Functional antagonism of chemokine receptor CCR1 reduces mortality in acute pneumovirus infection in vivo.
We present an antiviral-immunomodulatory therapeutic strategy involving the chemokine receptor antagonist Met-RANTES, which yields significant survival in the setting of an otherwise fatal respiratory virus infection. In previous work, we demonstrated that infection with the natural rodent pathogen pneumonia virus of mice involves robust virus replication accompanied by cellular inflammation modulated by the CC chemokine macrophage inflammatory protein 1alpha (MIP-1alpha). We found that the antiviral agent ribavirin limited virus replication in vivo but had no impact on morbidity and mortality associated with this disease in the absence of immunomodulatory control. We show here that ribavirin reduces mortality, from 100% to 10 and 30%, respectively, in gene-deleted CCR1(-/-) mice and in wild-type mice treated with the small-molecule chemokine receptor antagonist, Met-RANTES. As MIP-1alpha-mediated inflammation is a common response to several distantly related respiratory virus pathogens, specific antiviral therapy in conjunction with blockade of the MIP-1alpha/CCR1 inflammatory cascade may ultimately prove to be a useful, generalized approach to severe respiratory virus infection and its pathological sequelae in human subjects.


TESTS FOR ANCIENT SPECIES FLOCKS BASED ON MOLECULAR PHYLOGENETIC APPRAISALS OF SEBASTES ROCKFISHES AND OTHER MARINE FISHES.
The concept of species flocks has been central to previous interpretations of patterns and processes of explosive species radiations within several groups of freshwater fishes. Here, molecular phytogenies of species-rich Sebastes rockfishes from the northeastern Pacific Ocean were used to test predictions of null theoretical models that assume random temporal placements of phylogenetic nodes. Similar appraisals were conducted using molecular data previously published for particular cichlid fishes in Africa that epitomize, by virtue of a rapid and recent radiation of species, the traditional concept of an intralacustrine "species flock." As gauged by the magnitudes of genetic divergence in cytochrome b sequences from mitochondrial DNA, as well as in allozymes, most speciation events in the Sebastes complex were far more ancient than those in the cichlids. However, statistical tests of the nodal placements in the Sebastes phylogeny suggest that speciation events in the rockfishes were temporally nonrandom, with significant clustering of cladogenetic events in time. Similar conclusions also apply to an ancient complex of icefishes (within the Notothenioidei) analyzed in the same fashion. Thus, the rockfishes (and icefishes) may be interpreted as ancient species flocks in the marine realm. The analyses exemplified in this report introduce a conceptual and operational approach for extending the concept of species flocks to additional environmental settings and evolutionary timescales.


Kinesin family member 4A: a potential predictor for progression of human oral cancer.
Kinesin family member 4A (KIF4A), a microtubule-based motor protein, was implicated in regulation of chromosomal structure and kinetochore microtubule dynamics. Considering the functions of KIF4A, we assumed that KIF4A is involved in progression of oral squamous cell carcinomas (OSCCs) via activation of the spindle assembly checkpoint (SAC). However, little is known about the relevance of KIF4A in the behavior of OSCC. We investigated the KIF4A expression status and its functional mechanisms in OSCC. The KIF4A expression levels in seven OSCC-derived cells were analyzed by quantitative reverse transcriptase-polymerase chain reaction and immunoblotting analyses. Using a KIF4A knockdown model, we assessed the expression of (SAC)-related molecules (BUB1, MAD2, CDC20, and cyclin B1), cell-cycle, and cellular proliferation. In addition to in vitro data, the clinical correlation between the KIF4A expression levels in primary OSCCs (n = 106 patients) and the clinicopathologic status by immunohistochemistry (IHC) also were evaluated. KIF4A mRNA and protein were up-regulated significantly (P < 0.05) in seven OSCC-derived cells compared with human normal oral keratinocytes. In the KIF4A knockdown cells, SAC activation was observed via increased BUB1 expression on the kinetochores, appropriate kinetochore localization of MAD2, down-regulation of CDC20, up-regulation of cyclin B1, and cell-cycle arrested at G2/M phase. The results showed that cellular proliferation of KIF4A knockdown cells decreased significantly (P < 0.05) compared with control cells. IHC showed that KIF4A expression in primary OSCCs was significantly (P < 0.05) greater than in the normal oral counterparts and that KIF4A-positive OSCCs were correlated closely (P < 0.05) with tumoral size. Our results proposed for the first time that KIF4A controls cellular proliferation via SAC activation. Therefore, KIF4A might be a key regulator for tumoral progression in OSCCs.


Hemodialysis in patients with carcinoma.
All patients who underwent hemodialysis as part of their treatment for cancer at Roswell Park Memorial Institute from 1965 to 1974 were retrospectively studied to determine the value of hemodialysis in cancer patients. Approximately 25% (8 cases) lived 5 weeks or longer in spite of advanced renal failure and carcinoma with no severe complications. The longest survivor is still alive after ten years.


A Comparative Study of Hypofractionated and Conventional Radiotherapy in Postmastectomy Breast Cancer Patients.
The aim of this study was to compare toxicity and locoregional control of short duration hypofractionated (HF) radiotherapy (RT) with conventional RT in breast cancer patients. A total of 100 postmastectomy breast cancer patients were randomized for adjuvant RT in control group (comprising fifty patients who received the standard conventional dose of 50 Gy in 25 fractions with 2 Gy per fraction) and study group (comprising fifty patients who received HF RT with dose of 42.72 Gy in 16 fractions with 2.67 Gy per fraction). All patients were treated on linear accelerator with 3-dimensional conformal RT technique. Outcome was analyzed in terms of toxicity, tolerability, and locoregional control. In the present study, at a median follow-up of 20 months, almost similar results were seen in both the groups in terms of toxicity, tolerability, and locoregional control. Adjuvant postmastectomy HF RT was found to be well tolerated with mild-to-moderate side effects that neither reached statistical significance nor warranted any treatment interruption/hospitalization. HF postmastectomy RT is comparable to conventional RT without evidence of higher adverse effects or inferior locoregional tumor control and has an added advantage of increased compliance because of short duration; hence, it can help in accommodating more breast cancer patients in a calendar year, ultimately resulting in decreased waiting list, increased turnover, and reduced cost of treatment.


RNA under tension: Folding Landscapes, Kinetic partitioning Mechanism, and Molecular Tensegrity.
Non-coding RNA sequences play a great role in controlling a number of cellular functions, thus raising the need to understand their complex conformational dynamics in quantitative detail. In this perspective, we first show that single molecule pulling when combined with with theory and simulations can be used to quantitatively explore the folding landscape of nucleic acid hairpins, and riboswitches with tertiary interactions. Applications to riboswitches, which are non-coding RNA elements that control gene expression by undergoing dynamical conformational changes in response to binding of metabolites, lead to an organization principle that assembly of RNA is determined by the stability of isolated helices. We also point out the limitations of single molecule pulling experiments, with molecular extension as the only accessible parameter, in extracting key parameters of the folding landscapes of RNA molecules.


Influence of Flue Gas Injection on the Long-Term Durability of a Natural Draft Concrete Cooling Tower.
The article undertakes the very important topic of the long-term durability of concrete in a natural draft concrete cooling tower with flue gas injection. The corrosive conditions, including temperature, relative humidity, and CO2 and SO2 gas concentrations, near the inner wall of a cooling tower with flue gas injection were monitored in real time to obtain the long-term durability performance of concrete. The pH and chemical compositions of the condensed liquid that adhered to the tower's inner face and the macromorphology, compressive strength, and neutralization depth of in situ specimens were tested periodically. In addition, a finite element numerical simulation was conducted to simulate and verify the concentration distributions of CO2 and SO2 in the flue gas in the cooling tower. The results showed that the cleaned flue gas was enveloped, diluted, and uplifted by hot vapor in the cooling tower, and its concentration decreased. Meanwhile, the effective diffusion radius increased gradually as the flue gas rose. With the same elevation in the cooling tower, the concentration of flue gas decreased rapidly from the central point to the surrounding area. The air near the inner surface of the cooling tower was merely dampened air with a low concentration of acidic gas due to the gigantic diameter of the cooling tower. As a result, the injection of cleaned flue gas will not evidently increase the corrosion risk in a natural draft concrete cooling tower.


A sequential transformation approach to the internally contracted multireference coupled cluster method.
The internally contracted multireference coupled cluster (ic-MRCC) approach is formulated using a new wave function ansatz based on a sequential transformation of the reference function (sqic-MRCC). This alternative wave function simplifies the formulation of computationally viable methods while preserving the accuracy of the ic-MRCC approach. The structure of the sqic-MRCC wave function allows folding the effect of the single excitations into a similarity-transformed Hamiltonian whose particle rank is equal to the one of the Hamiltonian. Consequently, we formulate an approximation to the sqic-MRCC method with singles and doubles (included respectively up to fourfold and twofold commutators, sqic-MRCCSD[2]) that contains all terms present in the corresponding single-reference coupled cluster scheme. Computations of the potential energy curves for the dissociation of BeH(2) show that the untruncated sqic-MRCCSD scheme yields results that are almost indistinguishable from the ordinary ic-MRCCSD method. The energy obtained from the computationally less expensive sqic-MRCCSD[2] approximation is found to deviate from the full ic-MRCCSD method by less than 0.2 mE(h) for BeH(2), while, in the case of water, the harmonic vibrational frequencies of ozone, the singlet-triplet splitting of p-benzyne, and the dissociation curve of N(2), sqic-MRCCSD[2] faithfully reproduces the results obtained via the ic-MRCCSD scheme truncated to two commutators. A formal proof is given of the equivalence of the ic-MRCC and sqic-MRCC methods with the internally contracted and full configuration interaction approaches.


Private Financial Transfers, Family Income, and the Great Recession.
Using longitudinal data from the Fragile Families and Child Wellbeing Study (N = 4,701; 1998-2010), the authors studied whether the unemployment rate was associated with private financial transfers (PFTs) among urban families with young children and whether family income moderated these associations. They found that an increase in the unemployment rate was associated with greater PFT receipt and that family income moderated the association. Poor and near-poor mothers experienced increases in PFT receipt when unemployment rates were high, whereas mothers with incomes between 2 and 3 times the poverty threshold experienced decreases. Simulations estimating the impact of the Great Recession suggest that moving from 5% to 10% unemployment is associated with a 9-percentage-point increase in the predicted probability of receiving a PFT for the sample as a whole, with greater increases in predicted probabilities among poor and near poor mothers.


In vitro and in vivo biological activities of anthocyanins from Nitraria tangutorun Bobr. fruits.
Anthocyanins are the main compounds in Nitraria tangutorun Bobr. The enrichment and purification of anthocyanins on macroporous resins were investigated. Regarding anthocyanin purification, static adsorption and desorption were studied. The optimal experimental conditions were the following: resin type: X-5; static adsorption time: 6h; desorption solution: ethanol-water-HCl (80:19:1, V/V/V; pH 1); desorption time: 40min. Furthermore, the in vitro and in vivo biological activities of the anthocyanins were evaluated. The anthocyanins showed ideal scavenging effects on free radicals in vitro, especially on 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl free radical (OH). In the animal experiment, blood lipid metabolism of hyperlipidemia rats was regulated by anthocyanin contents. The superoxide dismutase (SOD) activity and the total antioxidant capacity (TAC) of hyperlipidemia rats were also improved by anthocyanins. These results showed that anthocyanins from N. tangutorun Bobr. fruits had potential biological activities in vivo as well as in vitro.


Hyperthermia induces multiple pancreatic heat shock proteins and protects against subsequent arginine-induced acute pancreatitis in rats.
Heat shock proteins (HSPs) which are induced by stress can provide protection against subsequent cellular damage. Whole body hyperthermia in rats leading to induction of HSP70 has been shown to protect against subsequent caerulein-induced acute pancreatitis. We studied the effect of hyperthermia on pancreatic HSP expression and found a significant increase in HSP70 (26.0-fold) and HPS27 (6.0-fold) but no change in HSP60, HSP90 or GRP78. Hyperthermia conferred significant protection against subsequent arginine-induced acute pancreatitis. More specifically, the degradation and disorganization of the actin cytoskeleton, an important early component of acute pancreatitis, was prevented. These results generalize previous work on caerulein-induced pancreatitis to another model of experimental pancreatitis, arginine-induced pancreatitis, and suggest that multiple HSPs may be involved in the cytoprotective effect in rat pancreas.


High doses of tyrosine kinase inhibitor PTK787 enhance the efficacy of ischemic hypoxia for the treatment of hepatocellular carcinoma: dual effects on cancer cell and angiogenesis.
The present study aimed to investigate the therapeutic efficacy of combining vascular endothelial growth factor (VEGF) receptor blockade using tyrosine kinase inhibitor PTK787 with hypoxia for the treatment of hepatocellular carcinoma (HCC). The in vivo effects of the treatments were determined in a rat orthotopic HCC model, in which hypoxia was generated by hepatic artery ligation (HAL). Compared with HAL alone, PTK787 combined with HAL significantly prolonged the animal survival, reduced the tumor size, induced more tumor tissue necrosis and apoptosis, and down-regulated the expression of von Willebrand factor. The mechanism was explored in vitro using murine HCC and endothelial cell lines, respectively. PTK787 combined with hypoxia decreased the expression of VEGF and VEGF receptors in both cell lines and suppressed the cell viability by induction of cell cycle arrest and promotion of apoptosis. Up-regulation of cleaved form caspase-9 and down-regulation of Bcl-2 and cyclin D1 were detected with the combined treatment. Hypoxia sensitized endothelial cells to the inhibitory effect of PTK787 on forming tubular-like structure. The motility of tumor cells was inhibited by hypoxia and the combined approach, with down-regulation of Rac1, Rho, and phosphorylated Akt expression. However, in the endothelial cells, the combined treatment inhibited the hypoxia-enhanced cell motility, with suppressed Rac1, Rho, and phosphorylated Akt expression. In conclusion, PTK787 combined with hypoxia achieved a better therapeutic efficacy than hypoxia alone through enhancing hypoxia-induced antitumor cell effect and preventing the activation of angiogenic process.


Shape controllable microgel particles prepared by microfluidic combining external ionic crosslinking.
Alginate microgels with varied shapes, such as mushroom-like, hemi-spherical, red blood cell-like, and others, were generated by combining microfluidic and external ionic crosslinking methods. This novel method allows a continuous fine tuning of the microgel particles shape by simply varying the gelation conditions, e.g., viscosity of the gelation bath, collecting height, interfacial tension. The release behavior of iopamidol-loaded alginate microgel particles with varied morphologies shows significant differences. Our technique can also be extended to microgels formation from different anionic biopolymers, providing new opportunities to produce microgels with various anisotropic dimensions for the applications in drug delivery, optical devices, and in advanced materials formation.


Taking a Stab at Cancer; Oncolytic Virus-Mediated Anti-Cancer Vaccination Strategies.
Vaccines have classically been used for disease prevention. Modern clinical vaccines are continuously being developed for both traditional use as well as for new applications. Typically thought of in terms of infectious disease control, vaccination approaches can alternatively be adapted as a cancer therapy. Vaccines targeting cancer antigens can be used to induce anti-tumour immunity and have demonstrated therapeutic efficacy both pre-clinically and clinically. Various approaches now exist and further establish the tremendous potential and adaptability of anti-cancer vaccination. Classical strategies include ex vivo-loaded immune cells, RNA- or DNA-based vaccines and tumour cell lysates. Recent oncolytic virus development has resulted in a surge of novel viruses engineered to induce powerful tumour-specific immune responses. In addition to their use as cancer vaccines, oncolytic viruses have the added benefit of being directly cytolytic to cancer cells and thus promote antigen recognition within a highly immune-stimulating tumour microenvironment. While oncolytic viruses are perfectly equipped for efficient immunization, this complicates their use upon previous exposure. Indeed, the host's anti-viral counter-attacks often impair multiple-dosing regimens. In this review we will focus on the use of oncolytic viruses for anti-tumour vaccination. We will explore different strategies as well as ways to circumvent some of their limitations.


Performance of Real-Time Polymerase Chain Reaction Assays for the Detection of 20 Gastrointestinal Parasites in Clinical Samples from Senegal.
Gastrointestinal parasite infections represent one of the biggest public health problems in the world. Therefore, appropriate innovative tools are needed for assessing interventions to control these infections. This study aims to compare the performance of real-time polymerase chain reaction (PCR) assays to microscopic examination for detection of intestinal parasites. A direct microscopic examination and stool concentration was performed on 98 stool samples from patients attending Senegalese hospitals. Negative microscopic control samples were also collected in Nice and Marseille (France). Species-specific primers/probes were used to detect 20 common gastrointestinal protozoans and helminths. Positive frequency and the sensitivity of each real-time PCR assay were compared with conventional microscopic examination. Real-time PCR was positive in 72 of 98 samples (73.5%), whereas microscopic examination was positive in 37 (37.7%) samples (P < 0.001). The real-time PCR assays were more sensitive than microscopy, with 57.4% (31/54) versus 18.5% (10/54), respectively, in the detection of parasites in asymptomatic patients (P < 0.05). In terms of polyparasitism, there were more coinfections detected by real-time PCR assays compared with microscopic methods (25.5% versus 3.06%). In comparison to parasite prevalence on individual samples, the results showed a perfect agreement (100%) between the two techniques for seven species, whereas discrepancies were observed for the others (agreement percentage varying from 64.2% to 98.9%). Real-time PCR appeared to be superior to microscopic examination for the detection of parasites in stool samples. This assay will be useful in diagnostic laboratories and in the field for evaluating the efficacy of mass drug administration programs.


Multidrug resistance to commonly prescribed antibiotics in Escherichia coli isolated from barbecued beef (Suya) sold in a Nigerian City.
Suya, a form of barbecued meat widely consumed in Nigeria is a rising source of concern for the dissemination of pathogens and antibiotic resistance. this study was carried out to determine the antibiotic resistance profile of Escherichia coli (E. coli) isolated from Suya sold in Karu Local Government Area, Nasarawa State, Nigeria. A total of three hundred (300) Suya samples were collected and screened for the presence of E. coli. An antibiotic susceptibility study was carried out on the isolated bacteria to determine their resistance profiles. the overall isolation and occurrence of E. coli was 13.3%. The isolated organisms were most resistant to Ampicillin (100%) followed by Amoxicillin/Clavulanic acid (95%), Ciprofloxacin (92.5%), Nitrofurantoin, Imipenem and Ceftriaxone (85%), Cefixime (80%), Streptomycin (77.5%), and Cotrimoxazole (77%), with a low level of resistance recorded against Gentamycin (5%). Most of the E. coli isolates had multiple resistance (MAR) to at least five antibiotics (MAR Index of = 0.5) and the most frequent MAR Index was 0.8 with 37.5% occurrence. The most frequently encountered resistance phenotype was Nitrofurantoin-Imipenem-Streptomycin-Ciprofloxacin-Ceftriaxone-Amoxicillin/clavulanic acid-Cefixime-Ampicillin. The E. coli isolates categorised based on drug resistance classes were Multi-Drug Resistance, MDR (97.5%), Pan Drug Resistance, PDR (2.5%), Non-Multi-Drug Resistance, NMDR (0.0%) and Extensive Drug Resistance, XDR (0.0%). these findings indicate a potential danger of multidrug resistant organisms in circulation. Antibiotics stewardship and drug resistance surveillance is strongly recommended for all stakeholders.


A nonparametric approach to QT interval correction for heart rate.
We propose to use generalized additive models to fit the relationship between QT interval and RR (RR = 60/heart rate), and develop two new methods for correcting the QT for heart rate: the linear additive model and log-transformed linear additive model. The proposed methods are compared with six commonly used parametric models that were used in four clinical trial data sets and a simulated data set. The results show that the linear additive models provide the best fit for the vast majority of individual QT-RR profiles. Moreover, the QT correction formula derived from the linear additive model outperforms other correction methods.


Effect of Hypoxia-regulated Polo-like Kinase 3 (Plk3) on Human Limbal Stem Cell Differentiation.
Hypoxic conditions in the cornea affect epithelial function by activating Polo-like kinase 3 (Plk3) signaling and the c-Jun·AP-1 transcription complex, resulting in apoptosis of corneal epithelial cells. Hypoxic stress in the culture conditions also regulates limbal stem cell growth and fate. In this study, we demonstrate that there is a differential response of Plk3 in hypoxic stress-induced primary human limbal stem (HLS) and corneal epithelial (HCE) cells, resulting in different pathways of cell fate. We found that hypoxic stress induced HLS cell differentiation by down-regulating Plk3 activity at the transcription level, which was opposite to the effect of hypoxic stress on Plk3 activation to elicit HCE cell apoptosis, detected by DNA fragmentation and TUNEL assays. Hypoxic stress-induced increases in c-Jun phosphorylation/activation were not observed in HLS cells because Plk3 expression and activity were suppressed in hypoxia-induced HLS cells. Instead, hypoxic stress-induced HLS cell differentiation was monitored by cell cycle analysis and measured by the decrease and increase in p63 and keratin 12 expression, respectively. Hypoxic stress-induced Plk3 signaling to regulate c-Jun activity, resulting in limbal stem cell differentiation and center epithelial apoptosis, was also found in the corneas of wild-type and Plk3(-/-)-deficient mice. Our results, for the first time, reveal the differential effects of hypoxic stress on Plk3 activity in HLS and HCE cells. Instead of apoptosis, hypoxic stress suppresses Plk3 activity to protect limbal stem cells from death and to allow the process of HLS cell differentiation.


Insulin Represses Fasting-Induced Expression of Hepatic Fat-Specific Protein 27.
The fat-specific protein 27 (Fsp27) gene belongs to the cell death-inducing DNA fragmentation factor 45-like effector family. Fsp27 is highly expressed in adipose tissue as well as the fatty liver of ob/ob mice. Fsp27 is directly regulated by the peroxisome proliferator-activated receptor γ (PPARγ) in livers of genetically obese leptin deficient ob/ob mice. In the present study, Fsp27 was markedly induced by 24 h fasting in genetically normal mouse livers and repressed by refeeding a high sucrose diet. In contrast with the liver, Fsp27 expression was decreased in adipose tissue by fasting and increased by refeeding. Interestingly, fasting-induced Fsp27 liver expression was independent of PPARγ. Moreover, Fsp27 expression was induced in the insulin-depleted livers of streptozotocin-treated mice. Finally, Fsp27 expression was repressed by direct injection of glucose or insulin in fasting mice. These results suggest that insulin represses Fsp27 expression in the fasting liver.


What does end stage in neuromuscular diseases mean? Key approach-based transitions.
To revise the definition of end stage in the setting of neuromuscular disease (NMD), to understand the implications for the patient, family and healthcare team, and to address the obstacles involved in the lack of definition. Unlike several conditions such as cancer, kidney or liver disease, the literature reveals no clear definition or categorization for NMD. Many articles mention end stage without defining it. Many years ago an expert consensus panel defined it based on functional criteria (forced vital capacity values and hypercapnic events). Only for amyotrophic lateral sclerosis/motoneurone disease has a wider criteria been proposed. As a consequence, the management of this heterogeneous group of disorders is often fragmented compared with the well organized palliative care program for cancer patients. Better end-stage NMD definitions should help to identify the goals of care, but a broad range in time and intensity of deterioration make a valid definition difficult for end-stage NMD. Respiratory care, life-prolonging therapies, and structured care planning should be seen as complementary rather than dichotomous. This article emphasized the relevance of an integrated approach through the whole trajectories of NMD patients considering key transitions.


Your duty to report.
Anyone raising a concern about colleague should be able to do so with the expectation that their concern will be taken seriously and dealt with appropriately, and that they themselves will be supported. As a registered nurse, you have a duty under the Nursing and Midwifery Council (NMC) code to raise concerns if you believe patient safety, or the safety of others, is at risk.


Uncovering spatiotemporal patterns of atrophy in progressive supranuclear palsy using unsupervised machine learning.
To better understand the pathological and phenotypic heterogeneity of progressive supranuclear palsy and the links between the two, we applied a novel unsupervised machine learning algorithm (Subtype and Stage Inference) to the largest MRI data set to date of people with clinically diagnosed progressive supranuclear palsy (including progressive supranuclear palsy-Richardson and variant progressive supranuclear palsy syndromes). Our cohort is comprised of 426 progressive supranuclear palsy cases, of which 367 had at least one follow-up scan, and 290 controls. Of the progressive supranuclear palsy cases, 357 were clinically diagnosed with progressive supranuclear palsy-Richardson, 52 with a progressive supranuclear palsy-cortical variant (progressive supranuclear palsy-frontal, progressive supranuclear palsy-speech/language, or progressive supranuclear palsy-corticobasal), and 17 with a progressive supranuclear palsy-subcortical variant (progressive supranuclear palsy-parkinsonism or progressive supranuclear palsy-progressive gait freezing). Subtype and Stage Inference was applied to volumetric MRI features extracted from baseline structural (T1-weighted) MRI scans and then used to subtype and stage follow-up scans. The subtypes and stages at follow-up were used to validate the longitudinal consistency of subtype and stage assignments. We further compared the clinical phenotypes of each subtype to gain insight into the relationship between progressive supranuclear palsy pathology, atrophy patterns, and clinical presentation. The data supported two subtypes, each with a distinct progression of atrophy: a 'subcortical' subtype, in which early atrophy was most prominent in the brainstem, ventral diencephalon, superior cerebellar peduncles, and the dentate nucleus, and a 'cortical' subtype, in which there was early atrophy in the frontal lobes and the insula alongside brainstem atrophy. There was a strong association between clinical diagnosis and the Subtype and Stage Inference subtype with 82% of progressive supranuclear palsy-subcortical cases and 81% of progressive supranuclear palsy-Richardson cases assigned to the subcortical subtype and 82% of progressive supranuclear palsy-cortical cases assigned to the cortical subtype. The increasing stage was associated with worsening clinical scores, whilst the 'subcortical' subtype was associated with worse clinical severity scores compared to the 'cortical subtype' (progressive supranuclear palsy rating scale and Unified Parkinson's Disease Rating Scale). Validation experiments showed that subtype assignment was longitudinally stable (95% of scans were assigned to the same subtype at follow-up) and individual staging was longitudinally consistent with 90% remaining at the same stage or progressing to a later stage at follow-up. In summary, we applied Subtype and Stage Inference to structural MRI data and empirically identified two distinct subtypes of spatiotemporal atrophy in progressive supranuclear palsy. These image-based subtypes were differentially enriched for progressive supranuclear palsy clinical syndromes and showed different clinical characteristics. Being able to accurately subtype and stage progressive supranuclear palsy patients at baseline has important implications for screening patients on entry to clinical trials, as well as tracking disease progression.


Rapid and selective access to three distinct sets of indole-based heterocycles from a single set of Ugi-adducts under microwave heating.
Three distinct sets of indole-based heterocycles were rapidly and selectively synthesized from the same set of Ugi-adducts under microwave heating in a reaction-condition-controlled manner. Notably, an unprecedented metal-free intramolecular sp(3)-hybridized C-H arylation using only cesium carbonate was discovered.


A Comparison of the Charlson and Elixhauser Methods for Predicting Nursing Indicators in Gastrectomy with Gastric Cancer Patients.
Background: Comorbidity indices such as Charlson's (CCI) and Elixhauser's (ECI) are used to adjust the patient's care, depending on the severity of their condition. However, no study has compared these indices' ability to predict nursing-sensitive outcomes (NSOs). We compared the performance of CCI and ECI in predicting NSOs in gastric cancer patients' gastrectomy. Methods: Gastric cancer patients with gastrectomy, aged 19 years or older and admitted between 2015 and 2016, were selected from the Korea Insurance Review and Assessment Service database. We examined the relationships between NSOs and CCI or ECI while adjusting patient and hospital characteristics with logistic regression. Results: The ECI item model was the best in view of the C-statistic and Akaike Information Criterion for total NSO, physiologic/metabolic derangement, and deep vein thrombosis, while the Charlson item model was the best for upper gastrointestinal tract bleeding. For the C-statistic, the ECI item model was the best for in-hospital mortality, CNS complications, shock/cardiac arrest, urinary tract infection, pulmonary failure, and wound infection, while the CCI item model was the best for hospital-acquired pneumonia and pressure ulcers. Conclusions: In predicting 8 of 11 NSOs, the ECI item model outperformed the others. For other NSOs, the best model varies between the ECI item and CCI item model.


The Effect of a Breastfeeding Motivation Program Maintained During Pregnancy on Supporting Breastfeeding: A Randomized Controlled Trial.
Exclusive breastfeeding is the recommended breastfeeding method for infants during the first 6 postnatal months. This study aimed to increase breastfeeding duration and frequency using a breastfeeding motivation program (BMP), which was structurally based on Pender's Health Promotion Model (HPM) and administered during pregnancy and the postnatal period. The study was also designed to determine the BMP effectiveness in supporting exclusive breastfeeding. The sample of this randomized controlled trial included 100 pregnant women (50 in the BMP, 50 in the control group) who applied to the pregnancy preparation course in a state hospital located in Usak, western Turkey. Participants in the study were allocated into either the BMP group or control group through systematic sampling and randomization. The BMP was structured based on the HPM and was carried out with the BMP study group four times: during the antenatal period, on the first postnatal day, between the fourth and sixth postnatal weeks, and during the fourth postnatal month. Data were analyzed using the descriptive statistical test, Pearson's chi-square test, independent samples t test, and ANOVA. The mothers in the BMP group started breastfeeding earlier than the mothers in the control group (97.1%) and had fewer problems with their first breastfeeding experience. The average score of perceived self-efficacy in breastfeeding and the rate of first breastfeeding experience (70.6%) were higher in the BMP group by a statistically significant amount. BMP for breastfeeding, structurally based on Pender's HPM, can help in supporting and maintaining exclusive breastfeeding.


Gastrointestinal motility disorders in scleroderma.
After the skin, the gastrointestinal tract is the second most common target of systemic sclerosis. The major clinical manifestations include gastroesophageal reflux, small bowel bacterial overgrowth, malnutrition, and intestinal pseudoobstruction. Treatment is symptomatic and supportive. Gastroesophageal reflux can usually be adequately managed with prokinetic drugs, omeprazole, and judicious use of antireflux surgery. If Barrett's esophagus is present, periodic endoscopic monitoring for development of dysplastic changes or adenocarcinoma is indicated. Bacterial overgrowth usually responds to rotating antibiotics and prokinetic drugs. Malnutrition and intestinal pseudoobstruction remain the major problems and often home total parenteral nutrition is required. Intestinal pseudoobstruction occurs in two phases: an early, neuropathic phase may respond to prokinetic drugs (metoclopramide, cisapride, octreotide, and erythromycin) and dietary modification (low-residue diets, vitamin supplementation). In the late myopathic phase, therapy is usually ineffective. Treatment consists of nutritional support. Careful manometric and radiographic localization of affected segments of stomach and small and large intestines may allow judicious surgical resection or venting procedures to reduce symptoms in this unfortunate group of patients.


Exploiting core knowledge for visual object recognition.
Humans recognize thousands of objects, and with relative tolerance to variable retinal inputs. The acquisition of this ability is not fully understood, and it remains an area in which artificial systems have yet to surpass people. We sought to investigate the memory process that supports object recognition. Specifically, we investigated the association of inputs that co-occur over short periods of time. We tested the hypothesis that human perception exploits expectations about object kinematics to limit the scope of association to inputs that are likely to have the same token as a source. In several experiments we exposed participants to images of objects, and we then tested recognition sensitivity. Using motion, we manipulated whether successive encounters with an image took place through kinematics that implied the same or a different token as the source of those encounters. Images were injected with noise, or shown at varying orientations, and we included 2 manipulations of motion kinematics. Across all experiments, memory performance was better for images that had been previously encountered with kinematics that implied a single token. A model-based analysis similarly showed greater memory strength when images were shown via kinematics that implied a single token. These results suggest that constraints from physics are built into the mechanisms that support memory about objects. Such constraints-often characterized as 'Core Knowledge'-are known to support perception and cognition broadly, even in young infants. But they have never been considered as a mechanism for memory with respect to recognition. (PsycINFO Database Record


The Green Prescription Active Families programme in Taranaki, New Zealand 2007-2009: Did it reach children in need?
The Green Prescription Active Families (GRxAF) programme focuses on overweight/obese children and adolescents, and is family/whanau based. It is an intervention supporting lifestyle changes through weekly sessions (nutrition advice and/or physical activity), and goal setting for the family/whanau for up to 12 months. To describe the GRxAF programme in Taranaki and evaluate its reach and engagement, especially for those most at risk of obesity. Participant files for each referred child from May 2007 to December 2009 were reviewed. Baseline demographic data, programme graduation information, and weekly activity session attendance were collected. Of the 109 participants during the audit period, 39% were Maori , 57% New Zealand European (NZE), 3% Pacific, and 1% Other ethnicity. Mean age at entry was 10 (range 4-17) years. Mean duration of programme involvement was five (range 0-12) months. Overall, 33/60 (55%) of the participants completing the programme during the audit period graduated, having made steps towards healthy lifestyle change. In comparison with NZE (68%), a smaller proportion of Maori (40%) graduated (p=0.04). In comparison with those who attended no sessions, participants who attended any sessions were more likely to make positive changes (OR=3.65, 95% CI 1.24-10.8). GRxAF in Taranaki met a need for some obese/overweight children, but not for all families/whanau, especially those over-represented in childhood obesity statistics. Programme delivery for Maori requires improvement, and assessment of readiness to make lifestyle change as an enrolment criteria for all participants is recommended.


A peptide disrupting the D2R-DAT interaction protects against dopamine neurotoxicity.
Dopamine reuptake from extracellular space to cytosol leads to accumulation of dopamine, which triggers neurotoxicity in dopaminergic neurons. Previous studies have shown that both dopamine D2 receptor (D2R) and dopamine transporter (DAT) are involved in dopamine neurotoxicity. However, blockade of either D2R or DAT causes side effects due to antagonism of other physiological functions of these two proteins. We previously found that DAT can form a protein complex with D2R and its cell surface expression is facilitated via D2R-DAT interaction, which regulates dopamine reuptake and intracellular dopamine levels. Here we found that an interfering peptide (DAT-S1) disrupting the D2R-DAT interaction protects neurons against dopamine neurotoxicity, and this effect is mediated by inhibiting DAT cell surface expression and inhibiting both caspase-3 and PARP-1 cleavage. This study demonstrates the role of the D2R-DAT complex in dopamine neurotoxicity and investigated the potential mechanisms, which might help better understand the mechanisms of dopamine neurotoxicity. The peptide may provide some insights to improve treatments for dopamine neurotoxicity and related diseases, such as Parkinson's disease, as well as methamphetamine- and 3,4-methsylenedioxy methamphetamine-induced neurotoxicity.


Similarity of hydrophobic properties of alpha-fetoprotein and albumin.
Human alpha-fetoprotein (AFP) and serum albumin (HSA) were studied by hydrophobic interaction chromatography. A close resemblance was observed both in the native state and after various perturbations (pH, salt and alcohol) indicating a significant similarity in their molecular structures. Both proteins displayed similar hydrophobic properties which apparently were different from those of other globular proteins. In agreement with the domain structure proposed by Brown (1976), our results indicated that surface nonpolar side chains of both the native HSA and AFP produced large hydrophobic areas located solely in crevices.


Ensemble-based release estimation for accidental river pollution with known source position.
Dispersion model is an important tool for decision makers to accurately assess risks and effectively plan countermeasures during river pollution accidents, but their applications suffer from significant modeling uncertainties, primarily due to the scarce information of the source. A fully sequential inverse estimation method is proposed to reconstruct the temporal release for accidental river pollution. The method is based on a one-dimensional advection-dispersion model in conjunction with the augmented ensemble Kalman filter method. Detailed analysis of the ensemble background error covariance (BEC) matrix is conducted to elucidate the "flow-dependent" mechanism, which enables the inversion method to simultaneously take into account the uncertainties in the hydrological parameters (mean flow velocity and longitudinal dispersion coefficient). The method is evaluated with six field tracer experiments with various mean flow velocities, ranging from 0.085 to 0.889ms-1, and also compared with the commonly used Tikhonov regularization inverse estimation method to demonstrate its performance improvement. The results indicate that it successfully reconstructs the temporal release and reduces the relative errors of the total release estimation by about 12.4% on average compared with the Tikhonov method, since the errors caused by the uncertainties in mean flow velocity and longitudinal dispersion coefficient are effectively alleviated.


High-dose methylprednisolone as initial therapy in patients with acute bronchospasm.
The use of steroids in treating acute respiratory obstruction is still controversial. In this double-blind controlled trial, we decided to examine the beneficial effects of a single large dose of methylprednisolone (MSSP), using objective criteria. In the emergency setting, methylprednisolone (30 mg/kg) has been shown to decrease the need for hospital admission in patients with acute bronchospasm. No difference in this improvement was seen among patients in the steroid-dependent or non-steroid-dependent populations. Based on our findings, we suggest that the early use of single-dose steroid therapy is appropriate treatment for patients with acute bronchospastic attacks.


Outcome of serious blunt cardiac injury.
Although serious blunt cardiac injury (BCI) is usually fatal, patients who reach the hospital alive can have a spectrum of abnormalities. We attempted to define the clinical features that helped identify serious BCI and to evaluate outcome. Patients with serious BCI at a level I trauma center were identified during a 3-year period. Twelve patients had serious BCI. Six patients had cardiac arrest, and six had unexplained hypotension. Specific injuries included acute myocardial rupture (two patients); valvular disruption (two); myocardial contusion associated with either cardiac failure (two), complex ventricular arrhythmias (two), or delayed myocardial rupture (one), or present at autopsy (two); and coronary artery thrombosis (one). Seven of eight patients who did not have associated fatal injuries survived. Electrocardiography suggested cardiac injury in all nine patients in whom it was done, and echocardiography was useful to establish the diagnosis in four of five patients. Creatine phosphokinase isoenzyme levels did not distinguish serious injuries. The outcome of serious blunt cardiac injury can be favorable if patients have signs of life on arrival at the hospital, the signs of injury are recognized promptly, and other injuries do not supervene.


Development and Implementation Path of Kindergarten Stem Educational Activities Based on Data Mining.
Early childhood education in China has given stem education constant attention and study. On the one hand, it has introduced many foreign research findings on stem education, such as curriculum practice, evaluation systems, teacher training, and so on; on the other hand, this paper investigates the localization implementation path of stem education based on the realities of kindergartens. This paper investigates the development and implementation path of kindergarten stem education activities using data mining, analyzes how the kindergarten stem education monitoring index system is developed and further improved using data mining algorithm, and determines the function path and mode of data mining algorithm in kindergarten stem education. It is expected to be used as a reference in the development and implementation of stem education and teaching activities. The development and implementation path of kindergarten stem educational activities based on data mining algorithm using data technology to realize continuous audit can not only improve the audit means and scope but also provide new research ideas for the expansion and innovation of audit work, which is useful in building a path model of kindergarten stem educational activities development and implementation.


Expression levels of IL-17 and TNF-α in degenerated lumbar intervertebral discs and their correlation.
The present study aimed to investigate the expression and roles of interleukin (IL)-17 and tumor necrosis factor (TNF)-α in intervertebral disc degeneration (IDD) and to identify the association between the effects of IL-17 and TNF-α in IDD. This may increase understanding of the pathogenic mechanism underlying IDD, and aid the development of alternative therapies. The experimental group consisted of 40 samples of nucleus pulposus tissue obtained from the intervertebral discs (IVDs) of patients with IDD by surgical intervention, and was further divided into an annulus fibrosus disrupted group, comprising 18 patients in which the external annulus was ruptured, and an annulus fibrosus intact group comprising 22 patients. The control group consisted of 20 samples of nucleus pulposus tissue from the IVDs of patients with traumatic lumbar disc fractures. The mRNA and protein expression levels of IL-17 and TNF-α in the 50 tissue samples were detected by semi-quantitative reverse transcription polymerase chain reaction and immunohistochemical staining, respectively, and the results were statistically analyzed. The IL-17 and TNF-α protein and mRNA expression levels in the annulus fibrosus disrupted and annulus fibrosus intact groups were both higher compared with those in the control group. In addition, the expression levels of IL-17 and TNF-α in the annulus fibrosus disrupted group were significantly higher compared with those in the annulus fibrosus intact group (P<0.01). A positive correlation was identified between the mRNA and protein expression levels of IL-17 and TNF-α in the experimental group (r=0.957, P<0.01). IL-17 and TNF-α may therefore be involved in the progression of human IDD, and may have synergistic effects in the development of IDD.


Current employment characteristics and career intentions of Lithuanian dentists.
The present survey explored the current employment profile and future career intentions of Lithuanian general dentists and specialists. A census sampling method was employed with data collected by means of a structured questionnaire that inquired about demographics, different employment-related aspects (practice type and location, working hours, perceived lack of patients, etc.), and future career intentions (intent to emigrate, to change profession, or the timing of retirement). The final response rate was 67.6% corresponding to 2,008 respondents. The majority of all dentists work full or part-time in the private dental sector, more than one third of them owns a private practice or rents a dental chair. A minority of dentists works in the public dental sector. According to the survey, 26.6% of general dentists and 39.2% of dental specialists works overtime (> 40 hours per week; P < 0.001) and practice in multiple clinics (1.4 ± 0.6 and 2.0 ± 1.2, respectively; P < 0.001). One third of general dentists (31.3%) and dental specialists (31.4%) stated to have a low number of patients (P > 0.05). The majority (68.9% of general dentists and 65.9% of dental specialists) plans to work after the retirement age (P > 0.05). Emigration as an option for their professional career is being considered by 10.8% of general dentists and 8.3% of dental specialists (P > 0.05). Working either full or part-time in private practices (OR = 4.3) and younger age (≤ 35 years; OR = 2.2) are the two strongest predictors for a perceived insufficient number of patients. One third of dentists in Lithuania work long hours and lack patients. Many dentists practice in multiple locations and plan to retire after the official retirement age. Some dentists and dental specialists plan to emigrate. The perceived shortcomings within the dental care system and workforce planning of dentists need to be addressed.


Metagenomic Insights Reveal the Microbial Diversity and Associated Algal-Polysaccharide-Degrading Enzymes on the Surface of Red Algae among Remote Regions.
Macroalgae and macroalgae-associated bacteria together constitute the most efficient metabolic cycling system in the ocean. Their interactions, especially the responses of macroalgae-associated bacteria communities to algae in different geographical locations, are mostly unknown. In this study, metagenomics was used to analyze the microbial diversity and associated algal-polysaccharide-degrading enzymes on the surface of red algae among three remote regions. There were significant differences in the macroalgae-associated bacteria community composition and diversity among the different regions. At the phylum level, Proteobacteria, Bacteroidetes, and Actinobacteria had a significantly high relative abundance among the regions. From the perspective of species diversity, samples from China had the highest macroalgae-associated bacteria diversity, followed by those from Antarctica and Indonesia. In addition, in the functional prediction of the bacterial community, genes associated with amino acid metabolism, carbohydrate metabolism, energy metabolism, metabolism of cofactors and vitamins, and membrane transport had a high relative abundance. Canonical correspondence analysis and redundancy analysis of environmental factors showed that, without considering algae species and composition, pH and temperature were the main environmental factors affecting bacterial community structure. Furthermore, there were significant differences in algal-polysaccharide-degrading enzymes among the regions. Samples from China and Antarctica had high abundances of algal-polysaccharide-degrading enzymes, while those from Indonesia had extremely low abundances. The environmental differences between these three regions may impose a strong geographic differentiation regarding the biodiversity of algal microbiomes and their expressed enzyme genes. This work expands our knowledge of algal microbial ecology, and contributes to an in-depth study of their metabolic characteristics, ecological functions, and applications.


Anticoagulant-induced breast hematoma.
Warfarin is the most commonly used oral anticoagulant and is widely prescribed to prevent thromboembolic events. Warfarin-dependent spontaneous breast hematoma is a very rare complication. Presently described is rare case of warfarin-induced breast hematoma.


How essential is the 'essential' active-site lysine in dihydrodipicolinate synthase?
Dihydrodipicolinate synthase (DHDPS, E.C. 220.127.116.11), a validated antibiotic target, catalyses the first committed step in the lysine biosynthetic pathway: the condensation reaction between (S)-aspartate beta-semialdehyde [(S)-ASA] and pyruvate via the formation of a Schiff base intermediate between pyruvate and the absolutely conserved active-site lysine. Escherichia coli DHDPS mutants K161A and K161R of the active-site lysine were characterised for the first time. Unexpectedly, the mutant enzymes were still catalytically active, albeit with a significant decrease in activity. The k(cat) values for DHDPS-K161A and DHDPS-K161R were 0.06 +/- 0.02 s(-1) and 0.16 +/- 0.06 s(-1) respectively, compared to 45 +/- 3 s(-1) for the wild-type enzyme. Remarkably, the K(M) values for pyruvate increased by only 3-fold for DHDPS-K161A and DHDPS-K161R (0.45 +/- 0.04 mM and 0.57 +/- 0.06 mM, compared to 0.15 +/- 0.01 mM for the wild-type DHDPS), while the K(M) values for (S)-ASA remained the same for DHDPS-K161R (0.12 +/- 0.01 mM) and increased by only 2-fold for DHDPS-K161A (0.23 +/- 0.02 mM) and the K(i) for lysine was unchanged. The X-ray crystal structures of DHDPS-K161A and DHDPS-K161R were solved at resolutions of 2.0 and 2.1 A respectively and showed no changes in their secondary or tertiary structures when compared to the wild-type structure. The crystal structure of DHDPS-K161A with pyruvate bound at the active site was solved at a resolution of 2.3 A and revealed a defined binding pocket for pyruvate that is thus not dependent upon lysine 161. Taken together with ITC and NMR data, it is concluded that although lysine 161 is important in the wild-type DHDPS-catalysed reaction, it is not absolutely essential for catalysis.


Global cerebral edema after subarachnoid hemorrhage: frequency, predictors, and impact on outcome.
Cerebral edema visualized by CT is often seen after subarachnoid hemorrhage (SAH). Inflammatory or circulatory mechanisms have been postulated to explain this radiographic observation after SAH. We sought to determine the frequency, causes, and impact on outcome of early and delayed global cerebral edema after SAH. We evaluated the presence of global edema on admission and follow-up CT scans in 374 SAH patients admitted within 5 days of onset to our Neurological Intensive Care Unit between July 1996 and February 2001. Using multivariate analysis, we identified predictors of global cerebral edema and evaluated the impact of global edema on outcome 3 months after onset with the modified Rankin Scale. Global edema was present on admission CT scans in 8% (n=29) and developed secondarily in 12% (n=44) of the patients. Global edema on admission was predicted by loss of consciousness at ictus and increasing Hunt-Hess grade. Delayed global edema was predicted by aneurysm size >10 mm, loss of consciousness at ictus, use of vasopressors, and increased SAH sum scores. Thirty-seven percent (n=137) of the patients were dead or severely disabled (modified Rankin Scale 4 to 6) at 3 months. Death or severe disability was predicted by any global edema, aneurysm size >10 mm, loss of consciousness at ictus, increased National Institutes of Health Stroke Scale scores, and older age. Global edema is an independent risk factor for mortality and poor outcome after SAH. Loss of consciousness, which may reflect ictal cerebral circulatory arrest, is a risk factor for admission global edema, and vasopressor-induced hypertension is associated with the development of delayed global edema. Critical care management strategies that minimize edema formation after SAH may improve outcome.