Components of the smooth pursuit function in deficit and nondeficit schizophrenia.
The diagnosis of schizophrenia likely encompasses a heterogeneous group of disorders, complicating the search for its causes. Studies of deficit schizophrenia represent an attempt to reduce this heterogeneity by identifying biologically distinct subgroups. Supplementing clinical phenotypes with biological markers of risk (e.g., eye-tracking and sensory-gating deficits) have also been used to reduce disease heterogeneity. In this study, we examined smooth pursuit eye movements in healthy controls (n = 37), and deficit (n = 18) and nondeficit (n = 32) patients with schizophrenia to determine what aspects of abnormal smooth pursuit are associated with the two patient groups, and which, if any, specifically mark the deficit phenotype. A small sample of relatives of deficit (n = 12) and nondeficit (n = 35) patients was also examined. Positive symptoms were equally present in deficit and nondeficit patients. Subtle, psychotic-like positive traits were also equally present in the relatives of both deficit and nondeficit probands, whereas negative symptoms were significantly more prevalent among the relatives of deficit probands. Deficits in predictive pursuit were present in both patient groups and both groups of relatives. Deficit patients showed significantly lower initiation acceleration. A similar pattern of results was seen in our pilot sample of relatives of deficit patients. These findings suggest that predictive smooth pursuit abnormality is associated with positive symptoms in schizophrenia, and that initiation abnormalities may be associated with the deficit syndrome.


Association of HLA-DRB1 and -DQ Alleles and Haplotypes with Type 1 Diabetes in Jordanians.
The Human Leukocyte Antigen (HLA) class II genes, particularly the HLADR and -DQ loci, have been shown to play a crucial role in Type 1 Diabetes (T1D) development. This study is the first to examine the contribution of the HLA-DR/DQ alleles and haplotypes to T1D susceptibility in Jordanians. Polymerase chain reaction sequence-specific primers (PCR-SSP) were used to genotype 41 Jordanian healthy controls and 50 insulin-dependent diabetes mellitus (IDDM) patients. The following alleles were found to be significant high risk alleles in T1D Jordanian patients: DRB1*04 (OR=3.95, p<0.001), DRB1*0301(OR=5.27, p<0.001), DQA1*0301 (OR=5.67, p<0.001), DQA1*0501(OR=3.18, p=0.002), DQB1*0201(OR=2.18, p=0.03), DQB1*0302 (OR=5.67, p<0.001). However, Jordanians harboring the DRB1*0701 (OR=0.37, p=0.01), DRB1*1101 (OR=0.2, p=0.01), DQA1*0505 (OR=0.31, p=0.02), DQA1*0103 (OR=0.33, p=0.04), DQA1*0201 (OR=0.45, p=0.04), DQB1*0301 (OR=0.23, p=0.001), DQB1*0501 (OR=0.18, p=0.009) alleles had a significantly lower risk of developing T1D. A strong positive association of DRB1*04-DQA1*0301-DQBl*0302 (OR=5.67, p<0.001) and DRB1*0301-DQA1*0501-DQB1*0201 (OR=6.24, p<0.001) putative haplotypes with IDDM was evident in Jordanian IDDM patients whereas DRB1*1101-DQA1*0505- DQB1*0301 (OR=0.23, p=0.03) was shown to have a protective role against T1D in Jordanians. Our findings show that specific HLA class II alleles and haplotypes are significantly associated with susceptibility to T1D in Jordanians.


Role of infections in miscarriage.
Infections with certain pathogens can lead to perinatal complications. Several infections have been also associated with an increased likelihood of miscarriage. This manuscript discusses these infections, their modes of transmission, the evidence linking them to an increased risk of miscarriage, and whether prevention or treatment strategies are available.


[Junctional reciprocating tachycardia with second degree A-V block (author's transl)].
Two cases of paroxysmal supraventricular tachycardia sustained by an atrioventricular junctional reentry mechanism are presented. During the electrophysiological study it was possible to induce paroxysms of tachycardia showing 3:2 Lucianai-Wenckebach type and 2:1 atrioventricular block. The site of the block, its functional nature and the possible involvement of an anterogradely blocked atrio-nodal or atrio-His accessory pathway in the reentry circuit are discussed.


Isolation and characterization of plasminogen activators from hyperplastic and malignant prostate tissue.
Plasminogen activators from prostate tissue were purified to apparent homogeneity by a procedure involving reverse ammonium sulfate gradient solubilization, chromatography on gelatine-Sepharose, gel filtration on Sephadex G-150, and chromatography on Con A-Sepharose as a final step. Two activators were obtained. The predominant one exhibited physicochemical, immunochemical and functional properties indistinguishable from human urinary high molecular weight urokinase. The other one, which amounted to about 20% was immunochemically related to tissue type plasminogen activator and its plasminogen activator activity was enhanced by addition of CNBr-fibrinogen fragments in a similar pattern as for the vascular plasminogen activator. The molecular weight, however, and enzymatic activities on the synthetic low molecular weight paranitroanilide substrates pyro-Glu-Gly-Arg-pNA and H-D-Ile-Pro-Arg-pNA were different to vascular plasminogen activator but similar to high molecular weight urinary urokinase.


Glycodeoxycholate transport in brush border membrane vesicles isolated from rat jejunum and ileum.
The transport of the bile salt, glycodeoxycholate, was studied in vesicles derived from rat jejunal and ileal brush border membranes using a rapid filtration technique. The uptake was osmotically sensitive, linearly related to membrane protein and resembled D-glucose transport. In ileal, but not jejunal, vesicles glycodeoxycholate uptake showed a transient vesicle/medium ratio greater than 1 in the presence of an initial sodium gradient. The differences between glycodeoxycholate uptake in the presence and absence of a Na+ gradient yielded a saturable transport component. Kinetic analysis revealed a Km value similar to that described previously in everted whole intestinal segments and epithelial cells isolated from the ileum. These findings support the existence of a transport system in the brush border membrane that: (1) reflects kinetics and characteristics of bile salt transport in intact intestinal preparations, and (2) catalyzes the co-transport of Na+ and bile salt across the ileal membrane in a manner analogous to D-glucose transport.


Detection of Leishmania DNA in phlebotomines captured in Campo Grande, Mato Grosso do Sul, Brazil.
Over the past years, leishmaniases have become a public health issue in the Brazilian state of Mato Grosso do Sul, particularly in Campo Grande, the state capital. The purpose of this study was to detect the presence of Leishmania DNA in the population of phlebotomine sandflies using DNA amplification by PCR. Insect captures were carried out from 4 pm. to 7 am for 4 consecutive days each month from October 2005 to September 2006 in 16 neighborhoods located in 7 urban regions of Campo Grande. Traps were placed indoors and in the vicinity of households. As many as 971 males and 203 females were collected. One hundred and five naturally fed females were identified and grouped as 1- to 4-specimen pools. DNA extraction was carried out using whole insects. Lutzomyia longipalpis predominated, accounting for 99.15% of the phlebotomines captured. Also found was Nyssomyia whitmani, the vector of tegumentary leishmaniasis. Abundance was greatest in the vicinity of households (69.8% of the phlebotomines captured). As revealed by PCR, parasites were present in 1.9% of the Leishmania spp. specimens investigated and confirmed for visceral leishmaniasis.


Platelet antibodies in thrombocytopenic patients.
Platelet antibodies either bound to the surface of platelets or free in the serum were sought in patients who had low platelet counts for a variety of reasons. They were detected by finding excess IgG on the surface of washed platelets either directly or after incubation of the serum with normal platelets. The technique used was a modification of that described recently (Dixon et al, 1975) in which the greater the amount of anti-IgG consumed by the reaction with platelets the less the subsequent lysis of sheep red cells coated with IgG. This test could be calibrated by adding known quantities of IgG to the antisera and thus the amount of bound IgG could be measured. Platelets from normal donors and those with thrombocytopenia due to non-immunological causes such as aplastic anaemia or acute leukaemia were found to have 15-70 ng IgG/10(7) platelets (mean 53 ng). 37 out of 38 thrombocytopenic patients in whom immune destruction of platelets was suspected were found to have excess IgG on their platelets ranging from 70 to 720 ng/10(7) (mean 297 ng, P less than 0.001) and there was a significant inverse correlation between this amount and the platelet count (r = 0.85, P less than 0.001). Antibody in the serum was found in 14 of 22 patients with 'idiopathic' thrombocytopenic purpura (ITP), three of four patients with underlying lymphoma and in all five cases of systemic lupus erythematosus (SLE). Four non-thrombocytopenic patients with autoimmune haemolytic anaemia (AIHA) due to IgG on the red cells were also studied and were shown to have no increase in platelet-bound IgG. Our results confirm the work of Dixon et al (1975) that platelet antibody as excess IgG can be readily detected on the surface of platelets in patients with immune thrombocytopenia. The clinical implications of these findings are discussed.


Molecular mechanisms of caffeine-mediated intestinal epithelial ion transports.
As little is known about the effect of caffeine, one of the most widely consumed substances worldwide, on intestinal function, we aimed to study its action on intestinal anion secretion and the underlying molecular mechanisms. Anion secretion and channel expression were examined in mouse duodenal epithelium by Ussing chambers and immunocytochemistry. Ca2+ imaging was also performed in intestinal epithelial cells (IECs). Caffeine (10 mM) markedly increased mouse duodenal short-circuit current (Isc ), which was attenuated by a removal of either Cl- or HCO3 - , Ca2+ -free serosal solutions and selective blockers of store-operated Ca2+ channels (SOC/Ca2+ release-activated Ca2+ channels), and knockdown of Orai1 channels on the serosal side of duodenal tissues. Caffeine induced SOC entry in IEC, which was inhibited by ruthenium red and selective blockers of SOC. Caffeine-stimulated duodenal Isc was inhibited by the endoplasmic reticulum Ca2+ chelator (N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine), selective blockers (ruthenium red and dantrolene) of ryanodine receptors (RyR), and of Ca2+ -activated Cl- channels (niflumic acid and T16A). There was synergism between cAMP and Ca2+ signalling, in which cAMP/PKA promoted caffeine/Ca2+ -mediated anion secretion. Expression of STIM1 and Orai1 was detected in mouse duodenal mucosa and human IECs. The Orai1 proteins were primarily co-located with the basolateral marker Na+ , K+ -ATPase. Caffeine stimulated intestinal anion secretion mainly through the RyR/Orai1/Ca2+ signalling pathway. There is synergism between cAMP/PKA and caffeine/Ca2+ -mediated anion secretion. Our findings suggest that a caffeine-mediated RyR/Orai1/Ca2+ pathway could provide novel potential drug targets to control intestinal anion secretion.


Review of 64 cases of death in children with Prader-Willi syndrome (PWS).
Several deaths have been reported in children with Prader-Willi syndrome (PWS) following treatment with growth hormone (GH). We collected all of the reports of deaths in PWS children, both in treatment and non-treatment groups, analyzed the causes of the death and compared the two groups. We conducted an exhaustive search for reports using bibliographic databases, toxicology pharmacovigilance databases, and personal communications. Sixty-four PWS children (42M/22F) aged from a few days to 19 years were identified, 28 received GH treatment. Our results show that respiratory disorders were the most common cause of death (respiratory insufficiency or infections) which were reported in 61% of the children (68% in GH-treated and 55.5% in -untreated patients). We found no significant differences in gender, prevalence of obesity or prevalence of sleep apnea, between the patients treated with GH and the untreated patients. Nevertheless, most of the deaths in GH-treated children (75%) occurred during the first 9 months after the initiation of GH treatment. Our analysis shows the high frequency of respiratory infections in both GH-treated and -untreated PWS children. The first 9 months of GH treatment seems to be a high-risk period emphasizing the need for comprehensive care before and during GH treatment.


Factors associated with clonal hematopoiesis and interaction with marrow environment.
Clonal hematopoiesis (CH) is an expansion of clones in individuals without any hematologic abnormalities, often carrying the driver mutations implicated in myeloid tumors, such as DNMT3A, TET2, and ASXL1. Most notably, CH is an age-related event, accounting for ~ 10% of cases in people over 60 years old. CH may also be correlated with a previous history of cancer treatment with chemotherapeutic drugs/radiation and infection episodes. The link between aging and CH acquisition is best explained by the enhanced inflammatory level in the bone marrow environment, which in turn expands hematopoietic cell clones with mutations in myeloid drivers. This positive feedback accounts for not only increased incidence of subsequent myeloid tumors in CH carriers but also for increased all-cause mortality and cardiovascular diseases (CVD). Recent evidence from large-scale epidemiological studies with genetic profiles, and mice models that recapitulate hematopoietic clones harboring driver gene mutations has revealed the detailed pathophysiology of CH clones represented by specific driver mutations, especially regarding expansion mechanisms under environmental factors and how they alter the environment. This review introduces the current knowledge of CH with a special focus on its interaction with the marrow environment.


Rapid and simple determination of sennoside A and B in rhei rhizoma by ion-pair high-performance liquid chromatography.
A simple and precise ion-pair high-performance liquid chromatographic method was developed for the determination of sennoside A and B in Rhei Rhizoma. A reversed-phase chromatographic system consisting of a chemically bonded ODS silica gel column with an acetate buffer (pH 5.0)-acetonitrile (68:32), containing 5 mM tetra-n-heptylammonium bromide, as the mobile phase was used. Sennoside A and B in this crude drug were separated and determined within 20 min after direct injection of the solution extracted with 70% methanol. The results for various samples are presented.


The PHY domain is required for conformational stability and spectral integrity of the bacteriophytochrome from Deinococcus radiodurans.
Bacteriophytochrome from Deinococcus radiodurans (DrBphP) is a plant phytochrome homolog. To investigate the interaction of chromophore and protein structure, we purified recombinant DrBphP and performed biochemical analyses. Differences of apo- and holo-protein in electrophoretic properties in native gels and their susceptibility to trypsin indicate changes in both the conformation and surface topography of this protein as a result of chromophore assembly. Furthermore, proteolysis to Pr and Pfr conformers displayed distinctive cleavage patterns with a noticeable Pr-specific tryptic fragment. Of interest, a prolonged tryptic digestion showed a more severe impact upon the Pfr form. Most importantly, when we assessed the extent of dark reversion to evaluate the role of the cleaved part, a rapidly accelerated reversion was observed upon cleavage at residues 329-505 corresponding to the PHY domain. Our data thus show that the PHY domain is necessary for the Pfr stabilization and spectral integrity of DrBphP.


Ultradispersed nanoarchitecture of SnS nanoparticles/reduced graphene oxide for enhanced sodium storage performance.
SnSanodes for Na-ions (NIBs) batteries are known for theirs significantly high theoretical capacities involving conversion reactions and alloying/dealloying mechanisms. However, the large volume expansion of the SnS materials during electrode reactions and the lowelectrical conductivity could cause severe structural degradation and electrodes pulverization, consequently resulting in capacity fading. In this study, Ultradispersed nanoarchitecture of SnS nanoparticles/reduced graphene oxide (SnS/rGO) is prepared by the in situ growing SnS nanoparticles on the graphene followed by the thermal treatment. When served as the anode materials for NIBs, the SnS/rGO composites can deliver anexcellent reversible capacity of 559mAhg-1 at a current density of0.2Ag-1 after 70 cycles and an outstanding rate capability of 456mAhg-1 at a current density of 2Ag-1. The excellent electrochemical properties could be attributed to: (1) The structural merits of the ultradispersed SnS nanoparticles. (2) The synergistic effects between SnS nanoparticles and graphene.Which not only provides robust protection against the aggregation and volume changes of the SnSnanoparticles, but also ensures high transport kinetics for both electrons and Na ions. Therefore, the obtained ultradispersed nanoarchitecture of SnS nanoparticles/reduced graphene oxide composites possesses great potential as anode materials for NIBs.


Utility Of Three-Dimensional Heads-Up Surgery In Cataract And Minimally Invasive Glaucoma Surgeries.
This study aimed to assess the utility of the three-dimensional (3D) heads-up visualization system for minimal incision cataract surgery (MICS) and minimally invasive glaucoma surgeries (MIGSs). Toric intraocular lens (IOL) implantation with phacoemulsification and trabecular microbypass stent implantation in patients with cataract and open-angle glaucoma were performed using the heads-up 3D visualization system combined with surgical navigation rather than the conventional microscope. This procedure was found to have the following advantages: the ability to clearly observe the anterior chamber angle image without requiring frequent focus adjustment owing to the extended depth of field and emphasized stereoscopic effect provided by this system and maintain the surgeon's posture. The feasibility and comfort of this system are greater than those of the conventional microscopic for performing MICS and MIGS.


The ambiguities of social inclusion in mental health: learning from lived experience of serious mental illness in Ghana and the occupied Palestinian territory.
Social inclusion of people living with serious mental illness is widely promoted. However, only limited consideration has been given to the meanings of social inclusion within different settings and the ways in which it is envisioned, negotiated, and practised. In this paper, we explore meanings and practises of social inclusion from the perspectives of people living with serious mental illness and their families in Ghana and Palestine and how this is shaped by differing political and socio-cultural contexts. This paper draws on comparative ethnographic research including participant observation and interviews with people living with mental illness and family members in Ghana and the occupied Palestinian territory. Data were triangulated and analysed using thematic analysis. Participants described experiences of social inclusion and participation within communities, home and family life, friendships and social life, and work and livelihoods. This revealed how such experiences were variously shaped by differing political contexts and socio-cultural norms and expectations within the two settings. These in turn intersected with aspects such as gender roles, age, and socio-economic status. Aspirations for inclusion included greater awareness and understanding within society, accompanied by opportunities and support for meaningful inclusion at the political as well as community level. Findings point to the value of a contextual understanding of social inclusion, taking account of the impact of the wider socio-cultural, political, and economic environment. They also point to the need for an intersectoral approach, beyond communities and mental health services, to provide meaningful opportunities and support for social inclusion.


Beginning of pancreatic islet isolation by collagenase digestion (personal reminiscences).
The beginning of pancreatic islet isolation by collagenase digestion is described in the form of personal account.


Sensory transduction in dorsal cutaneous mechanoreceptors of the frog, Rana pipiens.
Sensory transduction was studied in dorsal skin mechanoreceptors of the frog, Rana pipiens. The skin was clamped and stretched before being stimulated with the tip of a glass rod mounted on a servo-controlled loudspeaker. Afferent activity was recorded extracellularly from a dorsal cutaneous nerve. Three groups of sensory units could be identified by the size of their recorded action potentials and their response to mechanical stimuli. Action potential amplitudes for the three groups were: less than 50 microV (group I), 50-250 microV (group II) and greater than 300 microV (group III). Group II were selected for further study because of their amplitude and their resistance to fatigue. Three types of mechanical stimuli were used to examine the dynamic properties of group II receptors, steps, sinusoids, and band-limited random displacement. In each case the responses could be well fitted by a power-law model with a fractional exponent of time or frequency. Random stimulation of a large number of group II receptors showed considerable variability in their sensitivity and in their dynamic behavior, as measured by the fractional exponent of frequency. However, the distributions of these two parameters were both unimodal and strongly clustered around the modes, suggesting that the recordings were from a single class of receptors. Varying the temperature of the receptors had little effect on their sensitivity or dynamic properties. This is in contrast to findings on other mechanoreceptors. Doubling the potassium concentration in the bathing solution affected the dynamic properties of the receptors within 5 min but several distinct patterns of change in dynamic behavior were seen.(ABSTRACT TRUNCATED AT 250 WORDS)


Development and application of antibody microarray for lymphocystis disease virus detection in fish.
Lymphocystis disease virus (LCDV) is the causative agent of lymphocystis disease affecting marine and freshwater fish worldwide. Here an antibody microarray was developed and employed to detect LCDV in fish. Rabbit anti-LCDV serum was arrayed on agarose gel-modified slides as capture antibody, and Cy3-conjugated anti-LCDV monoclonal antibody (MAbs) was added as detection antibody. The signals were imaged with a laser chip scanner and analyzed by corresponding software. To improve the sensitivity, different substrate binders (poly-L-lysine, MPTS, aldehyde, APES and agarose gel modified slides, and commercially available amino-modified slides), markers (fluorescein isothiocyanate, Cy3, horseradish peroxidase, biotin or colloidal gold) conjugated to anti-LCDV Mabs, and storage time of the antibody were assessed. The results showed that the antibody microarrays based on agarose gel-modified slides gave a lower detection limit of 0.55μg/ml of LCDV when Cy3 and HRP conjugated anti-LCDV MAbs were used as detection antibody; and the lowest detectable LCDV protein concentration was 0.0686 μg/ml when streptavidin-biotin conjugated to anti-LCDV MAbs served as detection antibody. The developed antibody microarray proved to have a high specificity for LCDV detection and a shelf-life of more than 8 months at -20°C. Furthermore, the LCDV detection results of the microarray in fish gills or fins (n=50) presented a concordance rate of 100% with enzyme-linked immunosorbent assay (ELISA) and 98% with immunofluorescence assay technique (IFAT). These results revealed that the developed antibody microarray could serve as an effective tool for diagnostic and epidemiological studies of LCDV in fish.


Results from chemoradiotherapy for squamous cell cervical cancer with or without intracavitary brachytherapy.
The aim of this study is to compare the outcomes of intracavitary high-dose-rate brachytherapy (BT-IC) boost and external beam radiotherapy (EBRT) boost in patients treated with concomitant chemoradiotherapy for squamous cell carcinoma of the cervix. It is a retrospective review of 92 patients with stage IB1-IVA cervical cancer treated with concomitant chemoradiotherapy between 2008 and 2013. All patients received pelvic 3D conformal EBRT (range, 45-50.4 Gy) concomitant with weekly cisplatin (40 mg/m2), and a BT-IC boost (37 patients: 4 fractions of 6 Gy prescribed to a point A) to the tumor or a 3D conformal EBRT boost (55 patients: 16.2 Gy), if the former was not technically feasible. The 5-year overall survival and recurrence-free survival rates for both groups were 68% and 55%, respectively. The 5-year overall survival and recurrence-free survival were better and statistically significant in the BT-IC group with 82% and 79%, respectively, as compared to the EBRT group with 58% and 38%, respectively. In multivariate analysis controlling for maximum tumor dimension, lymph node status, and FIGO stage, EBRT boost was associated with a statistical significant increase in the risk of recurrence (HR: 3.56; 95% CI: 1.27-10.02; p = 0.016) and a trend towards an increase in the risk of death (HR: 3.14; 95% CI: 0.97-10.17; p = 0.056). Lymph node status was also significantly associated with a greater risk of recurrence. BT-IC boost was associated with a lower recurrence rate and better overall survival and recurrence-free survival. EBRT boost patients had a three-fold increase in the risk of recurrence. Brachytherapy is essential in the treatment of cervical cancer and improved alternatives are needed for patients who are not candidates for standard brachytherapy applicators.


P2-purinergic agonists stimulate phosphodiesteratic cleavage of phosphatidylcholine in endothelial cells. Evidence for activation of phospholipase D.
The effects of purinergic agonists on phosphatidylcholine (PC) breakdown and prostacyclin synthesis were investigated in cultured bovine pulmonary artery endothelial cells (BPAEC) prelabeled with [3H]choline and [14C]myristic acid. Both labels were selectively incorporated into PC. In BPAEC prelabeled with [3H]choline, ATP stimulated a rapid 5-fold increase in intracellular free [3H]choline. [3H]Choline formation was associated with a concomitant loss of 3H from PC, and it was not preceded by an increase in the 3H content of other PC degradation products. In BPAEC prelabeled with [14C]myristic acid, ATP stimulated a rapid increase in [14C]phosphatidic acid and [14C]diacylglycerol. These changes were associated with a loss of 14C from PC but not from phosphatidylinositol. In permeabilized BPAEC prelabeled with [3H]choline, ATP and guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) stimulated an increase in [3H]choline but not [3H]phosphocholine. The effects of ATP and GTP gamma S were synergistic at low GTP gamma S concentrations. Permeabilized BPAEC did not convert exogenous [3H]phosphocholine to [3H]choline. These data are consistent with the notion that purinergic agonists stimulate PC breakdown by a phospholipase D mechanism. This suggestion was supported by the observation that in the presence of ethanol, ATP stimulated the formation of [14C]phosphatidylethanol in BPAEC prelabeled with [14C]myristic acid. Several adenine nucleotides and related purine derivatives were compared for their effectiveness in stimulating PC breakdown and prostacyclin synthesis. The chemical specificity observed for the two responses indicated that both were mediated by the P2Y purinoceptor subtype. PC breakdown stimulated by ATP occurred prior to the maximum rate of release of prostacyclin into the medium. Taken together these data indicate that PC breakdown in endothelial cells stimulated with purinergic agonists is due, at least in part, to the activation of a phospholipase D that is coupled to purinoceptors by a guanine nucleotide-binding protein. In conjunction with previous data on the effects of bradykinin, these findings suggest an important role for PC breakdown in the mechanism of signal transduction in endothelial cells stimulated with Ca2+-mobilizing agonists.


Dental characteristics of patients with four different types of skeletal dysplasias.
Skeletal dysplasia (SD) comprises more than 450 separate disorders. We hypothesized that their dental features would be distinctive and investigated the tooth characteristics of four patients with different SDs. Four SD patients with molecularly confirmed diagnoses, Pt-1 acromicric dysplasia, Pt-2 hypophosphatasia and hypochondroplasia, Pt-3 cleidocranial dysplasia, and Pt-4 achondroplasia, were recruited. A tooth from each patient was evaluated for mineral density (micro-computerized tomography), surface roughness (surface profilometer), microhardness, mineral contents (energy-dispersive X-ray), and ultrastructure (scanning electron microscopy and histology), and compared with three tooth-type matched controls. Pt-1 and Pt-3 had several unerupted teeth. Pt-2 had an intact-root-exfoliated tooth at 2 years old. The lingual surfaces of the patients' teeth were significantly smoother, while their buccal surfaces were rougher, than controls, except for Pt-1's buccal surface. The patients' teeth exhibited deep grooves around the enamel prisms and rough intertubular dentin. Pt-3 demonstrated a flat dentinoenamel junction and Pt-2 had an enlarged pulp, barely detectable cementum layer, and ill-defined cemento-dentinal junction. Reduced microhardnesses in enamel, dentin, and both layers were observed in Pt-3, Pt-4, and Pt-1, respectively. Pt-1 showed reduced Ca/P ratio in dentin, while both enamel and dentin of Pt-2 and Pt-3 showed reduced Ca/P ratio. Each SD has distinctive dental characteristics with changes in surface roughness, ultrastructure, and mineral composition of dental hard tissues. In this era of precision dentistry, identifying the specific potential dental problems for each patient with SD would help personalize dental management guidelines.


'Improved sensitivity of direct microscopy for detection of acid-fast bacilli in sputum in developing countries.
Diagnosis of pulmonary tuberculosis depends on the bacteriological examination of sputum. Sputum smear microscopy is efficient and can confirm the disease. However, direct microscopy of sputum, though rapid, has low sensitivity. There is, therefore, an urgent need to develop rapid, much more sensitive and specific methods. In a field study we collected sputum samples from 488 tuberculosis suspects and compared the results of examining smears prepared after treatment with sodium hypochlorite (NaOCl) and concentration of bacteria by centrifugation and direct staining with Ziehl-Neelsen stain. Direct smears stained with auramine-phenol were the reference standard. The use of NaOCl increased the sensitivity from 43.4% to 76.3%, with a specificity of 100% for both methods. The method is simple and cheap. As a potent disinfectant, NaOCl also reduces the risk of laboratory-acquired infection. Its application would increase the efficiency of tuberculosis control programmes.


Diabetes and ovarian cancer: risk factors, molecular mechanisms and impact on prognosis.
Diabetes mellitus has been linked to a lower rate of cancer survival and an increase in the incidence of most malignancies. Investigations showed that diabetes might affect ovarian cancer (OC) prognosis and survival. Based on the current information, this study intends to review the risk factors, molecular pathways, and impact of diabetes on OC. The data was derived from online databases, including Web of Science, PubMed, and Scopus. The inclusion criteria were original studies, which included the risk factors, molecular mechanisms, and impact of diabetes on OC. The effect of different antidiabetic drugs was also discussed in this manuscript. All of the clinical, in vivo, and in vitro studies were included in the present study. The diagnosis of diabetes mellitus negatively affects the survival and prognosis in OC cases. The epidemiologic data shows that the risk of OC increases in patients with diabetes mellitus compared to the healthy population. Insulin-like growth factors family was raised in diabetic patients, which target several mechanisms, including targeting oxidative stress, angiogenesis, and tumor markers. Antidiabetic drugs such as metformin, sitagliptin, and rosiglitazone have a promising effect on elongation of survival and enhancement of prognosis in OC patients. Diabetes mellitus is a significant risk factor for OC in women, and it negatively impacts survival and prognosis. Molecular mechanisms such as IGF family, oxidative stress, and inflammatory cytokines have been identified to explain this relationship. Antidiabetic drugs like metformin, sitagliptin, and rosiglitazone have shown promise in improving survival and prognosis of OC patients.


Development of a Mandarin Expressive and Receptive Vocabulary Test for children using cochlear implants.
Cochlear implants (CIs) provide children with profound hearing loss access to sounds and speech. Research on the effects of CI on speech and language development in mainland China is scarce due to the lack of standardized tests. This study aims at developing a vocabulary measure, the Mandarin Expressive and Receptive Vocabulary Test (MERVT), for pre-school children with CIs. Using responses from 102 normal-hearing preschool children, the initial vocabulary set was subjected to analyses to identify items with appropriate levels of difficulty and discrimination. Norms on 245 normal-hearing children aged 1;6 to 3;11 were later collected based on the final set of the items. Evaluation of the test's psychometric properties revealed good internal consistency. Significant correlations between the total MERVT scores and the Gesell Developmental Scale scores, between the MERVT expressive and receptive subtest scores and the total scores, and the gradual increase in MERVT scores with age, provided evidence of construct validity. Results from 29 children with CIs were also examined for evidence of the MERVT's construct validity. There was a significant correlation between these children's MERVT scores and their scores from an intelligence test. The MERVT scores increased with an increase in the duration of CI use and in chronological age. With good reliability and strong validity, the test is recommended for use in the monitoring of language development in children with CI.


How to determine the efficiency of intermediate transfer in an interacting enzyme system?
A kinetic method, based upon measuring the transient time of coupled reactions, is proposed for the determination of the intermediate channel efficiency in a system of functionally interacting enzymes. The procedure rests upon a novel description in which the transient time is expressed as a function of channel efficiency and lifetime of the intermediate molecules. By this approach the reduction of transient time can be explained even if no changes in the kinetic parameters of the individual reactions occur. For determining channel efficiency, a linearized form has been evaluated and applied to the analysis of the kinetics of the aspartate aminotransferase-glutamate dehydrogenase coupled reaction, for which the data were taken from the literature [(1982) Eur. J. Biochem. 121, 511-517].


[Effect of isolation stress on ethanol pharmacokinetics in the blood of rats developing a taste for alcohol and in the stage of physical dependence on alcohol].
Head space chromatography was used to study the rate of ethanol excretion as a criterion of the activity of ethanol-oxidizing enzymatic system in rats. Isolation stress was shown to be one of the factors determining inclination to voluntary ethanol intake. The level of alcohol motivation directly correlated with the degree of stress. At the stage of physical dependence on ethanol the activity of ethanol-oxidizing enzymatic system and ethanol consumption were independent of the isolation stress, but related to profound biochemical and neurochemical variations.


Reliability and Validity of the Psychosocial Distress Questionnaire-Breast Cancer.
To evaluate the psychometric properties of the Psychosocial Distress Questionnaire-Breast Cancer (PDQ-BC) and to compare its referrals with the Distress Thermometer (DT). Group 1 (N = 54) and Group 2 (N = 80) completed the PDQ-BC. Group 2 also completed the DT, the Hospital Anxiety and Depression Scale (HADS), and World Health Organization Quality of Life instrument-100 (WHOQOL-100; n = 55). Moderate to high correlations (r ≥ .44, p < .001) were found between related facets of the PDQ-BC, WHOQOL-100, and DT. The subscales state anxiety and depressive symptoms (PDQ-BC) have a sensitivity of 87.5% and 78.6%, respectively, and a specificity of 81.1% and 73.0%, respectively, compared to the HADS. The PDQ-BC shows good construct validity, test-retest reliability, and sensitivity to change. The PDQ-BC has a satisfactory sensitivity and specificity of the subscales state anxiety and depressive symptoms.


[Perception of ENDS among French high school students in Nord and Pas-de-Calais].
Electronic nicotine delivery systems (ENDS) have been gaining popularity for over a decade, particularly among young people. The aim was to understand how these devices were perceived, in general and according to different characteristics: gender, smoking status, experimentation or possession of SEDEN. A cross-sectional observational study was conducted by an online questionnaire to 15 high schools between 14 May and 23 October 2021. Perception was assessed by a constructed score. In total, 772 responses from 10 high schools were analysed; 44.7% had already experimented with ENDS. The main reason for use was pleasure (33.8%). Only 15% of smokers or former smokers reported using ENDS to stop smoking as their main reason. The majority of ENDS (72.8%) are perceived as harmful. This negative perception is more important among women, non-smokers, non-experimenters and non-owners of ENDS. More than 50% of the respondents consider ENDS as distinct from tobacco. ENDS are perceived as potentially harmful and their use is often motivated by pleasure. Their perception as a practice distinct from smoking, combined with unknown long-term consequences, justifies increased vigilance in the face of the emergence of these new uses.


The 5S gene internal control region is B-form both free in solution and in a complex with TFIIIA.
Rhodes and Klug have recently proposed that the internal control region of the Xenopus 5S RNA gene adopts an A-type DNA structure in solution. This suggestion was based on a Fourier analysis of both the spacing of DNase I cutting sites and on the distribution of G residues in the DNA sequence. Both revealed a approximately 5.6-5.7-base periodicity which the authors interpreted as a structural repeat every half helical turn of A-type DNA. This contention was strengthened by the finding that a 9-base-pair (bp) double-stranded deoxyoligonucleotide corresponding to residues +81 to +89 of the 5S gene exhibits an A' RNA-like crystal structure. This region of DNA is of special interest as it forms the binding site for the 5S gene-specific transcription factor IIIA (TFIIIA). TFIIIA is a Zn2+-binding protein which interacts with both the internal control region of the gene and the 5S transcript. As base-paired regions of RNA are of the A type, it was reasonable to postulate that 5S DNA might also adopt this conformation. We report here that the circular dichroism (CD) spectrum of a synthetic 54-bp deoxyoligonucleotide corresponding to the TFIIIA binding site is similar to the CD spectrum of B-form DNA in solution. Further, DNA-TFIIIA complexes show an unaltered DNA CD component indicating no gross alteration in DNA structure on protein binding.


Prevalence and correlates of depression and anxiety among patients with tuberculosis at WolaitaSodo University Hospital and Sodo Health Center, WolaitaSodo, South Ethiopia, Cross sectional study.
Anxiety and depression are frequently and highly occurring mental disorders in patients with tuberculosis. When depression and anxiety co-morbid with tuberculosis, it leads to poor adherence to anti TB medication, which is important barrier to global control of tuberculosis & increases the risk of morbidity and mortality due to TB. Cross sectional study was conducted to assess prevalence and correlates of depression and anxiety among patients with TB at WolaitaSodo University Hospital and Sodo Health Center, WolaitaSodo, Ethiopia. Institution based cross-sectional study was conducted in 2014.A total of 417 TB patients, who had regular follow up at WolaitaSodo University Hospital and Sodo Health Center, WolaitaSodo, South Ethiopia, were recruited to assess depression and anxiety and its associated correlates. Depression and anxiety were assessed through face to face interviews by trained psychiatry nurses using the hospital anxiety and depression scale (HADS). Correlates for depression and anxiety were assessed using a structured questionnaire, Oslo social support scale and TB stigma Scale. The prevalence of depression and anxiety among patients with TB were 43.4% (181) and 41.5% (173) respectively. When we adjusted for the effect of potential confounding variables, patients who had co-morbid HIV infection [AOR = 5.90,(95% CI: 2.34,15.93)], poor social support [AOR = 18.06, (95% CI:11.21,25.45)] & perceived TB stigma [AOR = 10.86, (95% CI:10.26,23.47)] were more likely to have depression as compared to individuals who had no co-morbid HIV infection, good social support and no perceived TB stigma respectively. Patients who had co-morbid HIV infection [AOR = 9.61,(95% CI:3.56,25.96)], poor social support [AOR = 8.93,(95% CI: 5.01,15.94)], perceived TB stigma [AOR = 3.11,(95% CI:1.78,5.42)], being female [AOR = 1.72 (95% CI: 1.06, 2.95)], current substance use[AOR = 4.88, (95% CI: 1.79, 13.28)] and being on intensive phase of TB treatment [AOR = 1.91, (95% CI: 1.08, 3.39)] were more likely to have anxiety as compared to individuals who had no co-morbid HIV infection, good social support, no perceived TB stigma, being male and being on continuous phase of TB treatment respectively. Developing guidelines and training of health workers in TB clinics is useful to screen and treat depression and anxiety among TB patients.


Association of IQ scores and school achievement with suicide in a 40-year follow-up of a Swedish cohort.
Few studies have investigated the association of childhood IQ and school achievement with suicide. The aim of this study was to investigate the association of childhood IQ with suicide in a cohort of Swedish women and men. 21 809 subjects born in 1948 and 1953 who completed IQ and school tests at age 13 years have been followed until 2003. Information on paternal education and in-patient care for psychosis was linked using the Swedish personal identification number. There were 180 suicides amongst subjects with measured IQ. High IQ was associated with reduced suicide risk among men (OR per unit increase in age-adjusted model 0.90, 95% CI 0.83-0.99), while there was no statistical evidence of an association in women (OR 1.04, 95% CI 0.90-1.20). Among men with a history of psychosis, high IQ was associated with an increased risk of suicide. Low childhood IQ at age 13 years is associated with an increased risk of suicide in men but not in women; however, amongst those with psychosis, low IQ appears to be protective.


[Ligamentous elbow injuries-When is surgical treatment still indicated?]
The elbow joint is a hinge-type synovial joint and is the second most frequently dislocated joint in adults and the most frequently dislocated joint in children. To find the right treatment options a precise understanding of the injury pattern, anatomy, biomechanics and pathology (simple vs. complex dislocation) is essential for a good reconstruction of the function and to prevent chronic instability and pain. The differentiation between acute and chronic instability gives another variation in the treatment plan. According to the latest literature there are clear indications for surgery of a complex elbow dislocation, whereas for simple dislocations conservative treatment is preferentially recommended; however, when is the surgical treatment of a ligamentous elbow dislocation (still) indicated?


Exposure of the alga Pseudokirchneriella subcapitata to environmentally relevant concentrations of the herbicide metolachlor: Impact on the redox homeostasis.
This study investigated the effect of the herbicide metolachlor (MET) on the redox homeostasis of the freshwater green alga Pseudokirchneriella subcapitata. At low MET concentrations (≤40 μg L-1), no effects on algal cells were detected. The exposure of P. subcapitata to 45-235 μg L-1 MET induced a significant increase of reactive oxygen species (ROS). The intracellular levels of ROS were particularly increased at high (115 and 235 μg L-1) but environmentally relevant MET concentrations. The exposure of algal cells to 115 and 235 μg L-1 MET originated a decrease in the levels of antioxidants molecules (reduced glutathione and carotenoids) as well as a reduction of the activity of scavenging enzymes (superoxide dismutase and catalase). These results suggest that antioxidant (non-enzymatic and enzymatic) defenses were affected by the excess of MET. As consequence of this imbalance (ROS overproduction and decline of the antioxidant system), ROS inflicted oxidative injury with lipid peroxidation and damage of cell membrane integrity. The results provide further insights about the toxic modes of action of MET on a non-target organism and emphasize the relevance of toxicological studies in the assessment of the impact of herbicides in freshwater environments.


Comparison of the Sensititre YeastOne® dilution method with the Clinical Laboratory Standards Institute (CLSI) M27-A3 microbroth dilution reference method for determining MIC of eight antifungal agents on 102 yeast strains.
The Clinical Laboratory Standards Institute ([CLSI] formerly NCCLS) reference broth microdilution testing method (protocol M27-A3) was compared with a commercially available methods (Sensititre YeastOne(®)) by testing two quality control strains and 102 isolates of Candida sp. and Cryptococcus sp. against fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole, flucytosin, amphotericin B and caspofungin. Minimal inhibitory concentrations (MIC) endpoints were determined after 24h of incubation for Sensititre YeastOne(®) and after 24 and 48 h for CLSI microdilution method. Essential agreements between methods vary from 70.6 to 92.2%. Categorical agreements vary from 94.1% for 5FC to 72.6% for AMB. Sensititre YeastOne(®) reading appears to be useful for avoiding very major errors and this confirms the interest of this method for evaluating new antifungals activity in vitro.


LCP1 triggers mTORC2/AKT activity and is pharmacologically targeted by enzastaurin in hypereosinophilia.
Hypereosinophilia (HE) is caused by a variety of disorders, ranging from parasite infections to autoimmune diseases and cancer. Only a small proportion of HE cases are clonal malignancies, and one of these, the group of eosinophilia-associated tyrosine kinase fusion-driven neoplasms, is sensitive to tyrosine kinase inhibitors, while most subtypes lack specific treatment. Eosinophil functions are highly dependent on actin polymerization, promoting priming, shape change, and infiltration of inflamed tissues. Therefore, we investigated the role of the actin-binding protein lymphocyte cytosolic protein 1 (LCP1) in malignant and nonmalignant eosinophil differentiation. We use the protein kinase C-β (PKCβ) selective inhibitor enzastaurin (Enza) to dephosphorylate and inactivate LCP1 in FIP1L1-platelet-derived growth factor receptor α (PDGFRA)-positive Eol-1 cells, and this was associated with reduced proliferation, metabolic activity, and colony formation as well as enhanced apoptosis and impaired migration. While Enza did not alter FIP1L1-PDGFRA-induced signal transducer and activator of transcription 3 (STAT3), STAT5, and ERK1/2 phosphorylation, it inhibited STAT1Tyr701 and AKTSer473 (but not AKTThr308 ) phosphorylation, and short hairpin RNA knockdown experiments confirmed that this process was mediated by LCP1 and associated mammalian target of rapamycin complex 2 (mTORC2) activity loss. Homeobox protein HoxB8 immortalized murine bone marrow cells showed impaired eosinophilic differentiation upon Enza treatment or LCP1 knockdown. Furthermore, Enza treatment of primary HE samples reduced eosinophil differentiation and survival. In conclusion, our data show that HE involves active LCP1, which interacts with mTOR and triggers mTORC2 activity, and that the PKCβ inhibitor Enza as well as targeting of LCP1 may provide a novel treatment approach to hypereosinophilic disorders.


Continuous sampling of cerebrospinal fluid in the conscious rabbit.
A cannulation technique for continuous sampling of cerebrospinal fluid (CSF) in unanesthetized freely moving rabbits is described. A permanent stainless steel cannula constructed easily and inexpensively from commercially available material is placed into the third ventricle and fixed to the skull by anchoring screws and dental cement. This procedure allows a continuous CSF sampling with a flow rate of 11.2 +/- 4.5 microliters/min without any sign of disturbing the animal. The penetration of the third ventricle or the periodic drainage of CSF, during a one month period, does not result in a variation of CSF protein (356 +/- 20 mg/l), glucose (4.5 +/- 0.2 mmol/l) or lactate (1.80 +/- 0.05 mmol/l) concentrations. Our technique has some advantages for pharmacological or pharmacokinetic investigations. The third ventricle CSF data will complete that of cisterna magna or lateral ventricle CSF. This method allows studies in the same animal during a period of one month without any problem. Moreover, it lends itself to experiments in which physiological conditions are required.


Energy of adsorption interaction and surface coverage from polymer of various molecular structures.
Adsorption from solutions of mixtures of polymers which considerably differ by the parameter of thermodynamics flexibility (sigma) has been studied at various components ratio. Initial and equilibrium concentrations of solutions were determined, surface coverage (theta) and energy of adsorption interaction (Q, kJ/mol of segments) were estimated by means of IR spectroscopy. The objects of investigation were: cis-1,4-polybutadiene rubber (PB) and cellulose triacetate (CTA). Aerosil (fumed silica) was used as an adsorbent. Analysis of the experimental data testifies that polymer polarity and its affinity to the surface have the decisive influence on the adsorption. Polar stiff chain CTA has greater affinity to the surface of adsorbent and correspondingly has greater adsorption activity as compared with flexible, but nonpolar PB. The values of energy of adsorption interaction and surface coverage obtained under the adsorption from polymer systems first of all depend on whether the stiff chain polar component or flexible chain nonpolar component prevails in the system. Increase of concentration of the nonpolar PB flexible chain in the system results in diminishing of summary energy of adsorption interaction, but its great flexibility at the same components ratio provides the maximal values of surface coverage. The greater values of the surface coverage under the adsorption from the solutions of polymer mixtures in comparison with the individual solutions are explained by the simultaneous adsorption of both components for all concentration intervals.


Sequentially-targeted biomimetic nano drug system for triple-negative breast cancer ablation and lung metastasis inhibition.
As a breast cancer subtype with high mortality in women, the efficient treatment of Triple-negative breast cancer (TNBC) is still a challenge due to its unique metastatic mode and poor prognosis. In this study, we developed a biomimetic nanodelivery system (denoted as GTDC@M-R NPs) based on erythrocyte membrane (M)-camouflaged graphene oxide quantum dots (GOQDs, G) for TNBC therapy. The TAT (T) and RGD (R) peptides were used to endow targeting accumulation ability of Gamabufotalin (CS-6, C) and doxorubicin (DOX, D) in tumor tissue. In vitro assay indicated good biocompatibility, prolonged blood circulation time (3-fold longer than GT NPs), and effectively enhanced cell and nucleus targeting capability of this nanosystem. Fluorescence activated cell sorter (FACS) analysis indicated that the combination of DOX and CS-6 induced TNBC cell apoptosis more than 89 % under the ratio of 10:1. In vivo assay indicated that the accumulation of GTDC@M-R NPs in tumor sites increased about 2-fold compared to naked GTDC NPs, which was accompanied by high tumor apoptosis rates through blocking chemotherapy-activated cyclooxygenase-2 (COX-2) and enhancing DOX's anti-tumor activity of chemical drugs (85%). Moreover, comparing with the control, the average number of lung metastatic nodules in tumor-bearing mice reduced 84%, the molecular mechanism of which is related to the down expression of COX-2, matrix metalloproteinase 9 (MMP9) and vascular endothelial growth factor (VEGF). Taken together, our results proved that the developed GTDC@M-R NPs can inhibit the growth and suppress metastasis of TNBC, which broaden our insights into the application of combinational strategy for efficient TNBC therapy. STATEMENT OF SIGNIFICANCE: In this study, we developed a biomimetic nanodelivery system (denoted as GTDC@M-R NPs) based on erythrocyte membrane (M)-camouflaged graphene oxide quantum dots (GOQDs, G) for TNBC therapy. The TAT (T) and RGD (R) peptides were used to endow targeting accumulation ability of Gamabufotalin (CS-6, C) and doxorubicin (DOX, D) in tumor tissue. These GTDC@M-R NPs indicated synergistic chemotherapy against TNBC cells through the precise cell and nuclear targeting, immune escape, and improved DOX sensitivity. A effective inhibition of tumor growth and metastasis was achieved by inhibiting Bcl-2/BAX, COX-2 and VEGF related signal pathways. Our finding suggests that the developed GTDC@M-R NPs present great treating effects in the preclinical models of TNBC, which broaden our insights into the application of combinational strategy for efficient TNBC therapy.


Vertically unstable sacral fractures with neurological insult: outcomes of surgical decompression and reconstruction plate internal fixation.
During a 4-year period, 32 patients with type C unstable sacral fractures were treated in our university hospital. All patients had neurological deficits as a result of their sacral fracture. The average age was 31.2 (range 22-54) years and the average Hannover Polytrauma Score (PTS) was 24 (range 19-40) points. Twelve patients had zone I fracture, ten had zone II fracture and ten patients had comminuted fractures involving both zones. All patients underwent surgical decompression and reconstruction plate internal fixation. The average follow up period was 24.4 (range 19-47) months. Twenty-one patients (65.6%) had complete neurological recovery, eight patients (25%) had partial recovery and three patients (9.4%) had no recovery. The relationship between radiological and functional scores was evident but insignificant (P = 0.434). Significantly, the neurological recovery was less favourable in older age groups, pedestrian trauma, vertical shear injuries, comminuted fractures, fifth lumbar root involvement, very low motor power grades and in patients presenting late. Concerning complications, four patients (12.5%) had early infection and five patients (15.6%) had late urological problems and heterotopic ossification. Consequently, we conclude that patients undergoing very early surgical decompression and only reconstruction plate internal fixation can achieve safe early ambulation and better neurological, functional and radiological results.


1,4-Dihydropyridine activators and antagonists: structural and functional distinctions.
The dihydropyridine series of drugs contains both potent antagonists and potent activators of Ca2+ channels. The structural differences between antagonists and activators are small and, indeed, activators can behave as antagonists at high levels of membrane depolarization. Here, David Triggle and David Rampe describe recent insights into the factors--including structure of the drug and activation state of the channel--that influence the behavior of these drugs, and discuss models that have been proposed to describe their mechanism of action.


A simple method for calculating mosquito mortality rates, correcting for seasonal variations in recruitment.
A simple age-structured exponential growth model is presented for the analysis of the population dynamics of mosquitoes (Diptera: Culicidae). In this model, the proportion of parous mosquitoes R depends on the birth rate beta, and the length of the first gonotrophic cycle g, but not on the mortality rate. If the age structure is fairly constant, R = exp(- betag). Extensions of the model correcting for feeding patterns are given. A simple method is applied to an example of Anopheles gambiae Giles biting density and parity ratio in Cĵte d'Ivoire (fortnightly sampled longitudinal data set), for calculation of the seasonally fluctuating mortality rate, correcting for effects of recruitment. The seasonal variations in birth rate and mortality rate are discussed in relation to variations in density and rainfall.


HIV transmission risk among HIV seroconcordant and serodiscordant couples: dyadic processes of partner selection.
Selecting sex partners of the same HIV status or serosorting is a sexual risk reduction strategy used by many men who have sex with men. However, the effectiveness of serosorting for protection against HIV is potentially limited. We sought to examine how men perceive the protective benefits of factors related to serosorting including beliefs about engaging in serosorting, sexual communication, and perceptions of risk for HIV. Participants were 94 HIV negative seroconcordant (same HIV status) couples, 20 HIV serodiscordant (discrepant HIV status) couples, and 13 HIV positive seroconcordant (same HIV status) couples recruited from a large gay pride festival in the southeastern US. To account for nonindependence found in the couple-level data, we used multilevel modeling which includes dyad in the analysis. Findings demonstrated that participants in seroconcordant relationships were more likely to believe that serosorting reduces concerns for condom use. HIV negative participants in seroconcordant relationships viewed themselves at relatively low risk for HIV transmission even though monogamy within relationships and HIV testing were infrequent. Dyadic analyses demonstrated that partners have a substantial effect on an individual's beliefs and number of unprotected sex partners. We conclude that relationship partners are an important source of influence and, thus, intervening with partners is necessary to reduce HIV transmission risks.


Interferon pretreatment inhibits simian virus 40 infections by blocking the onset of early transcription.
CV-1 cells treated with human leukocyte interferon before infection with simian virus 40 (SV40) are protected from virus-induced cytopathic effects. Accumulation of viral mRNA is inhibited markedly. If T antigen is present in interferon-treated cells before infection, viral DNA replication is inhibited only slightly. These results show that many SV40 virions reach the nucleus in a form which can be replicated but not transcribed. Accumulation of SV40 mRNA is not inhibited in cells treated with interferon after infection. Thus the block mediated by interferon is specific for the onset of transcription. Infections with SV40 DNA rather than virions are insensitive to treatment with interferon, showing that the inhibition involves an interaction between viral nucleoprotein complexes and cellular factors.


Historical case of dwarfism: attempted diagnosis.
A brief description is given of a male dwarf painted by the Italian artist Geromo Induno in 1852. This portrayal seems not to have been mentioned previously in the medical literature. Several experts were consulted in an attempt to diagnose the underlying skeletal dysplasia. Most opted for pseudoachondroplasia, with the most detailed argument coming from the subject of this Festschrift.


Periodontal disease: associations with diabetes, glycemic control and complications.
This report reviews the evidence for adverse effects of diabetes on periodontal health and periodontal disease on glycemic control and complications of diabetes. MEDLINE search of the English language literature identified primary research reports published on (a) relationships between diabetes and periodontal diseases since 2000 and (b) effects of periodontal infection on glycemic control and diabetes complications since 1960. Observational studies provided consistent evidence of greater prevalence, severity, extent, or progression of at least one manifestation of periodontal disease in 13/17 reports reviewed. Treatment and longitudinal observational studies provided evidence to support periodontal infection having an adverse effect on glycemic control, although not all investigations reported an improvement in glycemic control after periodontal treatment. Additionally, evidence from three observational studies supported periodontal disease increasing the risk for diabetes complications and no published reports refuted the findings. The evidence reviewed supports diabetes having an adverse effect on periodontal health and periodontal infection having an adverse effect on glycemic control and incidence of diabetes complications. Further rigorous study is necessary to establish unequivocally that treating periodontal infections can contribute to glycemic control management and to the reduction of the burden of diabetes complications.


Congenital colonic varices in the adult. Report of a case.
This study was conducted to report a rare cause of colonic bleeding. Case report. Surgical resection of congenital colonic varices is associated with a low incidence of morbidity and mortality, and a favorable long-term prognosis can be expected when there is no evidence of hepatocellular disease (portal hypertension).


Time-related changes in the Q-T interval in acute myocardial infarction: possible relation to local hypocalcemia.
In 63 patients with either acute transmural or nontransmural myocardial infarction, the Q-T interval was prolonged beyond normal limits on at least 1 of the 5 days after infarction in 27 patients (8 with transmural and 19 with nontransmural infarction). The time-related changes in the corrected Q-T (Q-Tc) interval were defined for the entire sample and showed significant expansion, maximal on day 2, from a preinfarction control value. By day 5, the Q-Tc interval was no longer significantly prolonged and was not expanded beyond normal limits in any patient. Various possible causes of Q-T prolongation in myocardial infarction are local hypothermia, local conduction delay, neurogenic effect and local hypocalcemia. Collateral evidence suggests that the letter may contribute significantly to prolongation.


Impact of pexelizumab, an anti-C5 complement antibody, on total mortality and adverse cardiovascular outcomes in cardiac surgical patients undergoing cardiopulmonary bypass.
During cardiac surgery requiring cardiopulmonary bypass, pro-inflammatory complement pathways are activated by exposure of blood to bio-incompatible surfaces of the extracorporeal circuit and reperfusion of ischemic organs. Complement activation promotes the generation of additional inflammatory mediators thereby exacerbating tissue injury. We examined the safety and efficacy of a C5 complement inhibitor for attenuating inflammation-mediated cardiovascular dysfunction in cardiac surgical patients undergoing cardiopulmonary bypass. Pexelizumab (Alexion Pharmaceuticals, Inc, Cheshire, CT), a recombinant, single-chain, anti-C5 monoclonal antibody, was evaluated in a randomized, double-blinded, placebo-controlled, multicenter trial that involved 914 patients undergoing coronary artery bypass grafting with or without valve surgery requiring cardiopulmonary bypass. Pexelizumab was administered intravenously as a bolus (2.0 mg/kg) or bolus plus infusion (2.0 mg/kg plus 0.05 mg/kg/h for 24 hours), and inhibited complement activation. There were no statistically significant differences between placebo-treated and pexelizumab-treated patients in the primary endpoint (composite of death, or new Q-wave, or non-Q-wave [myocardial-specific isoform of creatine kinase > 60 ng/mL] myocardial infarction, or left ventricular dysfunction, or new central nervous system deficit). However, post hoc analysis revealed a reduction in the composite of death or myocardial infarction (myocardial-specific isoform of creatine kinase >/= 100 ng/mL) for the isolated coronary artery bypass grafting, bolus plus infusion subgroup on POD 4 (p = 0.007) and on POD 30 (p = 0.004). Pexelizumab had no statistically significant effect on the primary endpoint. However, the reduction in death or myocardial infarction (myocardial-specific isoform of creatine kinase >/= 100 ng/mL) as revealed in the post hoc analysis in the isolated coronary artery bypass grafting bolus plus infusion subpopulation, suggests that further investigation of anti-C5 therapy for ameliorating complement-mediated inflammation and myocardial injury is warranted.


Contact lens prescribing trends in the UK hospital eye service.
The aim of this study was to evaluate the types of contact lenses fitted by hospital optometrists within the Midlands region of the United Kingdom (UK). A questionnaire was sent to all the lead optometrists of the Midlands Hospital Optometry Group (MHOG). This group includes optometry hospital eye departments within the Midlands region of the UK. The questionnaire requested information of their last ten contact lens fitting appointments. Details of the patient's age, gender, lens type, wearing times, and presenting condition were retrospectively taken from the patients' records using the appointment diary to identify the last ten patients fitted with contact lenses. Details from a total of 109 contact lens fits were collected. This included 45 females and 64 males with a mean age of 39.4 ± 17.4 years. The mean wearing time was 6.3 ± 1.0 days per week and 10.7 ± 5.1 h per day. Sixty-one percent of the contact lenses fitted were for patients with keratoconus and over half of all the contact lenses fitted were corneal rigid gas permeable lenses. This study highlighted that the main reason for fitting contact lenses in hospital contact lens practice is primary corneal ectasia, and mainly keratoconus. Whilst most patients with keratoconus were fitted with corneal rigid gas permeable contact lenses, around 1 in 6 were fitted with soft contact lenses. This study addresses a gap in the literature about contact lenses fitted in UK hospitals and how they differ from community contact lens practice.


[Ultrasonics in endodontics. 2. Clinical applications].
The present study, second of three dwelling with ultrasonic in endodontic therapy, is a review of the literature about clinical applications of some of the sonic and ultrasonic system.


Current Perspectives Regarding Institutional Conflict of Interest : Commentary on "Institutional Conflicts of Interest in Academic Research".
Policies and processes dealing with institutional conflict of interest (iCOI) lag well behind those dealing with individual COI. To remediate this, academic institutions must develop strategies for addressing some of the unique challenges in iCOI, including: clarifying the definition of iCOI that addresses the range of individuals potentially involved; implementing a well-designed electronic database for reporting and managing iCOI across multiple leadership constituencies; and providing ongoing education to appropriate institutional officials that communicates the importance of managing iCOI.


Second-line treatment options in metastatic castration-resistant prostate cancer: a comparison of key trials with recently approved agents.
Standard first-line treatment for metastatic castration-resistant prostate cancer (mCRPC) is docetaxel plus prednisone; however, patients will usually experience disease progression during or after docetaxel treatment due to inherent or acquired resistance. Before 2010, second-line options for mCRPC were limited. However, cabazitaxel, abiraterone acetate and enzalutamide have since been approved for patients with mCRPC whose disease has progressed during or after receiving docetaxel, based on the Phase III trials TROPIC, COU-AA-301 and AFFIRM. In all three trials, an overall survival benefit (primary endpoint) was seen in the experimental arm compared with the control arm: 15.1 vs. 12.7months for cabazitaxel plus prednisone compared with mitoxantrone plus prednisone in TROPIC (hazard ratio [HR] 0.70; P<0.0001); 14.8 vs. 10.9months for abiraterone acetateplus prednisone compared with placebo plus prednisone in COU-AA-301 (HR 0.65; P<0.001); and 18.4 vs. 13.6months for enzalutamide compared with placebo alone in AFFIRM (0.63; P<0.001). However, differences in patient populations, comparators, and selection and/or definition of secondary endpoints make it difficult to draw direct cross-trial comparisons. Radium-223 dichloride has also been approved for patients with mCRPC with metastases to bone but not other organs. To date, no comparative trials or sequencing studies with newer agents have been performed. Without such data, treatment decisions must be based on evaluation of the existing evidence. This commentary compares and contrasts study designs and key data from each of these Phase III trials, and also discusses recent and ongoing clinical trials with new agents in the first- and second-line settings in mCRPC.


Novel PCR-based methods enhance characterization of vaginal microbiota in a bacterial vaginosis patient before and after treatment.
Deep characterization, even by next-generation sequencing, of the vaginal microbiota in healthy women or posttreatment bacterial vaginosis patients is limited by the dominance of lactobacilli. To improve detection, we offer two approaches: quantitative PCR (qPCR) using phylogenetic branch-inclusive primers and sequencing of broad-spectrum amplicons generated with oligomers that block amplification of lactobacilli.


The certification process in adolescent medicine.
The first and second certifying examinations in adolescent medicine were administered jointly by the American Board of Pediatrics (ABP) and the American Board of Internal Medicine (ABIM) on November 15, 1994, to 295 candidates, and on November 18, 1997, to 197 candidates including 170 who were taking the examination for the first time. This report describes the certification process and the characteristics of those taking the first and second examinations in adolescent medicine. The purposes of certification in adolescent medicine, consistent with the purposes of specialty boards, are to improve the quality of patient care during the second decade of life, expand and improve training to include a comprehensive and scientifically based approach to the care of young people as they enter adulthood, and stimulate faculty development and research for the problems of the adolescent population (1). Certification addresses these goals by establishing rigorous standards for training, verifying the knowledge base of candidates through a written examination, and requiring periodic recertification. This certification program recognizes a growing number of physicians with expertise in the medical problems of adolescents and the emergence in the past 30 years of a body of knowledge about the health problems, the effects of rapid biologic and psychologic change, and the interaction of biologic, psychologic, social, and environmental forces that characterize this unique developmental period (2).


Evaluation of a part-time adult diploma nursing programme - 'Tailor-made' provision?
Part-time pre-registration nursing programmes aim to widen participation to female mature students and to reduce tension between domestic and study roles by 'tailoring' provision to the perceived needs of this group but there is little evidence of whether these aims are achieved. Findings are presented from an evaluation of a part-time pre-registration adult diploma nursing programme which suggest that this programme was successful in widening participation to female mature students but did not succeed in reducing role conflict for female mature students. The authors relate these findings to the literature and conclude that that this second aspect of tailoring may be difficult to achieve due to socio-economic changes, particularly increased female participation in the workforce.


The clinical importance of high-sensitivity cardiac troponin measurements for risk prediction in non-cardiac surgery.
The global healthcare burden associated with surgery is substantial, with many patients experiencing perioperative complications. Cardiac troponin I and T measured with high-sensitivity assays are cardiac specific biomarkers that associate closely with adverse outcomes in most patient populations. Perioperative physiological stress can induce troponin release from cardiomyocytes, a condition known as perioperative myocardial injury (PMI). PMI is associated with increased risk of poor short- and long-term outcomes, and current European guidelines recommend screening for PMI in at-risk individuals undergoing non-cardiac surgery. In this review we summarize current knowledge of the prognostic attributes of cardiac troponins, as well as the challenges associated with their application as biomarkers in the perioperative phase. Measurement of circulating levels of cardiac troponins identify individuals at increased risk of poor postoperative outcomes. Systematic screening of at-risk individuals undergoing non-cardiac surgery will result in a large proportion of patients in need of further diagnostic workup to establish the exact nature of their PMI. The lack of concrete evidence of clinical benefit and the increased cost associated with such a strategy is concerning and underscore the need for further research.


PM2.5 carbonaceous components and mineral dust at a COALESCE network site - Bhopal, India: Assessing the impacts of COVID-19 lockdowns on site-specific optical properties.
Thermal elemental carbon (EC), optical black carbon (BC), organic carbon (OC), mineral dust (MD), and 7-wavelength optical attenuation of 24-hour ambient PM2.5 samples were measured/estimated at a regionally representative site (Bhopal, central India) during a business-as-usual year (2019) and the COVID-19 lockdowns year (2020). This dataset was used to estimate the influence of emissions source reductions on the optical properties of light-absorbing aerosols. During the lockdown period, the concentration of EC, OC, BC880 nm, and PM2.5 increased by 70 % ± 25 %, 74 % ± 20 %, 91 % ± 6 %, and 34 % ± 24 %, respectively, while MD concentration decreased by 32 % ± 30 %, compared to the same time period in 2019. Also, during the lockdown period, the estimated absorption coefficient (babs) and mass absorption cross-section (MAC) values of Brown Carbon (BrC) at 405 nm were higher (42 % ± 20 % and 16 % ± 7 %, respectively), while these quantities for MD, i.e., babs-MD and MACMD values were lower (19 % ± 9 % and 16 % ± 10 %), compared to the corresponding period during 2019. Also, babs-BC-808 (115 % ± 6 %) and MACBC-808 (69 % ± 45 %) values increased during the lockdown period compared with the corresponding period during 2019. It is hypothesized that although anthropogenic emissions (chiefly industrial and vehicular) reduced drastically during the lockdown period compared to the business-as-usual period, an increase in the values of optical properties (babs and MAC) and concentrations of BC and BrC, were likely due to the increased local and regional biomass burning emissions during this period. This hypothesis is supported by the CBPF (Conditional Bivariate Probability Function) and PSCF (Potential Source Contribution Function) analyses for BC and BrC.


THRIL mediates endothelial progenitor cells autophagy via AKT pathway and FUS.
This study focused on the roles of lncRNA THRIL in coronary atherosclerotic heart disease (CAD) through regulating AKT signaling pathway and directly interacting with FUS. QRT-PCR was conducted to detect the expression of THRIL in CAD blood samples and endothelial progenitor cells (EPCs). Cell autophagy of EPCs was examined through Cyto-ID Autophagy Detection Kit. CCK-8 assay and flow cytometry were carried out to assess cell viability and apoptosis under various interference conditions. Western blotting was conducted to detect the expression of interest proteins. The expression levels of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were measured by qRT-PCR. The direct interactions between HCG18 and FUS was confirmed through RNA electrophoretic mobility shift assay (RNA EMSA) and RNA immunoprecipitation (RIP) assay. THRIL was upregulated in CAD blood samples and EPCs. Knockdown of THRIL in EPCs promoted cell viability, inhibited cell autophagy and further suppressed the development of CAD. Over-expression of THRIL induced inactivation of AKT pathway, while knockdown of THRIL played reversed effects. THRIL directly interacted with FUS protein and knockdown of FUS reversed the over-expressing effect of THRIL on cell proliferation, autophagy and the status of AKT pathway. THRIL inhibits the proliferation and mediates autophagy of endothelial progenitor cells via AKT pathway and FUS.


Manifestations of Indirect Self-Destructiveness and Dimensions of Emotional Intelligence.
While indirect self-destructiveness exerts a rather negative influence on the life and psychological and social functioning of the individual, emotional intelligence may have a favourable effect. The aim of this study has been to explore possible relationships between manifestations of indirect self-destructiveness and dimensions of emotional intelligence. A population of 260 individuals (130 females and 130 males) aged 20-30 (mean age of 24.5) was studied by using the Polish version of the Chronic Self-Destructiveness Scale and INTE, i.e., the Polish version of the Assessing Emotions Scale. Manifestations of indirect self-destructiveness show many significant correlations with variables of the INTE, and those correlations are negative. Generally, it can be said that low emotional intelligence is associated with poor psychosocial and social functioning, which, in turn, is associated with indirect self-destructiveness and its manifestations. It seems advisable to use emotional intelligence in the prophylactic and therapeutic work with individuals suffering from various types of disorders, especially the syndrome of indirect self-destructiveness.


Modification to Systemic Anticancer Therapy at the Start of the COVID-19 Pandemic and its Overall Impact on Survival Outcomes in Patients with Colorectal Cancer.
Since the beginning of the COVID-19 pandemic, multiple changes to the provision of cancer care has been introduced to maximize patient safety and protect staff. We aimed to identify factors influencing clinicians' decision on treatment modification during the initial phase of the pandemic, and to assess its impact on outcomes in patients with colorectal cancer. Electronic records of patients seen in a large United Kingdom tertiary cancer center was reviewed. The frequency and type of changes to systemic anticancer therapy , as well as the factors predicting clinicians' decision were assessed. A total of 418 patients; mean age 63 ± 12 years and 57% male were included. More than half of the patients had modification to their treatment; with treatment delay (21%) or cancellation (10%), being the most common. Majority of patients on neoadjuvant treatment (97%) proceeded with treatment, with some form of treatment modification in 20%. Half of patients on adjuvant treatment had their treatment plan modified. Overall, a change in treatment was more likely in older patients (OR 1.028 [95% CI 1.010-1.047]; P = .002), and in patients who had already received higher number of cycles of systemic anticancer therapy (OR 1.040 [95% CI 1.016-1.065]; P = .001). A change in treatment was less likely further out of the first national lockdown (OR 0.837 [95% CI 0.758-0.925]; P < .001). Patients on third-line treatment were most likely to have alterations to their treatment plan (69%, n=33/48). During the first wave of COVID-19 in the United Kingdom, clinicians adapted clinical practice in accordance to local and national guidance, especially amongst older patients and those on third-line treatment. Further real-world data are needed to document the important impact of changes to treatment on outcomes in patients with cancer.


Evolution in geriatric syndromes and association with survival over 5 years in the GERODIAB cohort of older French diabetic patients.
Although one in three patients with diabetes in Western countries is over 70 years-old, geriatric syndromes and their relationship with survival remain seldom studied. The present aim of the GERODIAB study was to examine the evolution of geriatric disorders and their relationship with survival in older type 2 patients with diabetes with initial sufficient autonomy. We performed a prospective, observational study over 5 years in patients with diabetes aged 70 years or above. A total of 987 consecutive type 2 patients with diabetes (mean age 77 years, range 70-94 years, 65.2% were 75 years and above, 52.1% women) were included from 56 French diabetic centres. Individual characteristics, diabetes parameters and geriatric parameters (autonomy, nutrition, cognitive alteration, depression, orthostatic hypotension, falls) were annually recorded. Survival was analysed using the Kaplan-Meier method and proportional hazards regression models. Institutional living, impaired activity and difficulties in instrumental daily activity, cognitive disorders, malnutrition, depression, orthostatic hypotension and hypoglycaemia strongly increased during the follow-up. Institutional living, impaired activity and difficulties in instrumental daily activity, cognitive disorders and hypoglycaemia were strongly associated with reduced survival, but not falls. In hazard ratio models, living in an institution (HR = 2.39; CI = 1.77-3.24; p < 0.0001) and impaired Activity of Daily Living scale score were the most significant and independent predictors of death (HR = 1.59; CI = 1.19-2.13; p = 0.0016), associated with HbA1c ≥ 70 mmol/mol (HR = 1.62; CI = 1.12-2.36; p = 0.011). Our findings show the considerable alteration of geriatric parameters and their relationship with decreased survival after a 5-year follow-up in type 2 patients with diabetes, independent of HbA1c and age. They, therefore, confirm the prognostic interest of using yearly geriatric markers in older diabetic patient management, especially the ADL, IADL and MMSE scales. Taking into account these prognostic parameters should contribute to target appropriate HbA1c goals. Registered at clinicaltrials.gov (21/01/2011): NCT01282060.


Advances in Swallowing Neurophysiology across Pediatric Development: Current Evidence and Insights.
This review article analyzes current evidence on the neurophysiology of swallowing during development and offers expert opinion on clinical implications and future research directions. In the past five years, basic and clinical research has offered advances in our understanding of pediatric swallowing neurophysiology. Animal models have elucidated the role of brainstem circuits and the peripheral and central nervous system in neonatal swallowing. Recent human studies have further showcased that fetal and infant swallowing require cerebral inputs in order to develop functionally. Finally, neurophysiological and neuroimaging studies are starting to better define these cerebral inputs, as well as neuroplastic adaptations that may be needed for optimal feeding development. The neural development of swallowing is a complex and dynamic process. Continued research is needed to better understand influences on swallowing neural development, which can be essential for improving prevention, diagnosis, and interventions for pediatric dysphagia.


Effects of HMGB1 on PMN apoptosis during LPS-induced acute lung injury.
To observe the effects of intravenous injection of HMGB1 inhibitor sodium butyrate on changes in apoptosis of PMN during LPS-induced acute lung injury in rats and HMGB1 in vitro on human circulating PMN apoptosis, in order to clarify the role of HMGB1 in the pathogenesis of acute lung injury. (1) LPS-induced acute lung injury rat model was developed by LPS infusion. At different time-points after LPS challenge in the presence or absence of sodium butyrate (SB), the rat tissue sample, peripheral blood PMNs and BALF were collected. RT-PCR was applied to examining rat lung tissue HMGB1 mRNA expression level, and Western blotting analysis was adopted to determine expression of rat lung tissue HMGB1 protein. PMN apoptotic changes were determined by flow cytometric (FCM) analysis, Giemsa staining and TdT-mediated dUTP nick end labeling (TUNEL) method. (2) Separated and purified human circulating PMN were coincubated for 24 h with different doses of HMGB1 (0, 10, 100, 1000 ng/ml, respectively) at 37 degrees C in 5% CO(2). PMN apoptosis rate was determined by flow cytometric (FCM) analysis and by TdT-mediated dUTP nick end labeling (TUNEL) method. (1) The percentage of apoptosis of PMN in rat model of LPS-induced ALI was gradually decreased as compared with that of normal control. The PMN apoptosis-initiation time and non-survival time in rat BALF prolonged significantly as compared with that of normal control. The injured rat lung tissue HMGB1 mRNA and protein expression was upregulated 6-24 h after LPS exposure; SB intervention significantly ameliorated the upregulation. In addition, the morphologic examination indicated that the edema severity and pathological changes of lung tissues were excessively aggravated in rats after LPS administration. By comparison, SB treatment diminished the severity of lung damage. Combined with lung HMGB1 expression level, the above changes indicate that the pathological changes of lung tissue were related to the injured lung HMGB1 expression, as well as apoptotic changes in PMN. (2) After coincubation of HMGB1 with human circulating PMNs, TUNEL and flow cytometry were performed. The study revealed that PMN apoptosis ratios was (40.53+/-4.12) % in control group (PMNs+RPMI 1640 medium), (19.05+/-2.44) % in LPS group (PMNs+RPMI 1640 medium+10 microg/ml LPS), (40.52+/-2.73) % in HMGB1-1 group (PMNs+RPMI 1640 medium+10 ng/ml HMGB1), (34.89+/-1.15) % in HMGB1-2 group (PMNs+RPMI 1640 medium+100 ng/ml HMGB1), and (18.77+/-3.02) % in HMGB1-3 group (PMNs+RPMI 1640 medium+1 000 ng/ml HMGB1). There was statistical significance. Meanwhile, PMN TUNEL positive rate was (31.42+/-4.40) %, (31.39+/-3.80) %, (25.62+/-2.46) %, and (17.98+/-3.20) % in control group, HMGB1-1 group, HMGB1-2 group and HMGB1-3 group, respectively. The inhibitory effect was HMGB1 dose-depended as compared with that of control group. After LPS challenge, high expression of rats' lung HMGB1 mRNA occurs at a later phase, but keeps for a long time. Sodium butyrate (SB) treatment attenuated LPS-induced PMN apoptosis delay and inhibition, and down-regulated HMGB1 mRNA expression of injured lung. HMGB1 in vitro inhibited human circulating PMN apoptosis markedly, and the inhibitory effect was HMGB1 dose-depended. The results demonstrated that HMGB1 may play an important role as a modulator in apoptotic changes in PMN during LPS-induced ALI. It concludes that HMGB1 may contribute to the development of PMN apoptotic changes during LPS-induced acute lung injury.


Knockdown of Stromal Interaction Molecule 1 (STIM1) Suppresses Acute Myeloblastic Leukemia-M5 Cell Line Survival Through Inhibition of Reactive Oxygen Species Activities
This study aimed to investigate the role of the stromal interaction molecule 1 (STIM1) gene in the survival of the acute myeloblastic leukemia (AML)-M5 cell line (THP-1). The STIM1 effect was assessed via dicersubstrate siRNA-mediated STIM1 knockdown. The effect of STIM1 knockdown on the expression of AKT and MAPK pathway-related genes and reactive oxygen species (ROS) generation-related genes was tested using real-time polymerase chain reaction. Cellular functions, including ROS generation, cell proliferation, and colony formation, were also evaluated following STIM1 knockdown. The findings revealed that STIM1 knockdown reduced intracellular ROS levels via downregulation of NOX2 and PKC. These findings were associated with the downregulation of AKT, KRAS, MAPK, and CMYC. BCL2 was also downregulated, while BAX was upregulated following STIM1 knockdown. Furthermore, STIM1 knockdown reduced THP-1 cell proliferation and colony formation. This study has demonstrated the role of STIM1 in promoting AML cell proliferation and survival through enhanced ROS generation and regulation of AKT/MAPK-related pathways. These findings may help establish STIM1 as a potential therapeutic target for AML treatment.


Low intensity focused ultrasound: a new prospect for the treatment of Parkinson's disease.
Background: As a chronic and progressive neurodegenerative disease, Parkinson's disease (PD) still lacks effective and safe targeted drug therapy. Low-intensity focused ultrasound (LIFU), a new method to stimulate the brain and open the blood-brain barrier (BBB), has been widely concerned by PD researchers due to its non-invasive characteristics.Methods: PubMed was searched for the past 10 years using the terms 'focused ultrasound', 'transcranial ultrasound', 'pulse ultrasound', and 'Parkinson's disease'. Relevant citations were selected from the authors' references. After excluding articles describing high-intensity focused ultrasound or non-Parkinson's disease applications, we found more than 100 full-text analyses for pooled analysis.Results: Current preclinical studies have shown that LIFU could improve PD motor symptoms by regulating microglia activation, increasing neurotrophic factors, reducing oxidative stress, and promoting nerve repair and regeneration, while LIFU combined with microbubbles (MBs) can promote drugs to cross the BBB, which may become a new direction of PD treatment. Therefore, finding an efficient drug carrier system is the top priority of applying LIFU with MBs to deliver drugs.Conclusions: This article aims to review neuro-modulatory effect of LIFU and the possible biophysical mechanism in the treatment of PD, summarize the latest progress in delivering vehicles with MBs, and discuss its advantages and limitations.


In vivo molecular imaging of apoptosis and necrosis in atherosclerotic plaques using microSPECT-CT and microPET-CT imaging.
The purpose of this paper is to study molecular imaging of apoptosis and necrosis, two key players in atherosclerosis instability, using a multimodal imaging approach combining single photon emission computed tomography (SPECT), positron emission tomography (PET), and computed tomography (CT). Collar-induced carotid atherosclerosis ApoE knockout mice were imaged with (99m)Tc-AnxAF568 SPECT-CT to study apoptosis and sequentially with PET-CT following (124)I-Hypericin ((124)I-Hyp) injection to visualize necrosis. SPECT depicted increased (99m)Tc-AnxAF568 uptake in both atherosclerotic carotid arteries, whereas our data suggest that this uptake is not merely apoptosis related. Although PET of (124)I-Hyp was hampered by the slow blood clearance in atherosclerotic mice, (124)I-Hyp was able to target necrosis in the atherosclerotic plaque. Both (99m)Tc-AnxAF568 and (124)I-Hyp uptake are increased in atherosclerotic carotid vasculature compared to control arteries. While apoptosis imaging remains challenging, necrosis imaging can be feasible after improving the biodistribution characteristics of the probe.


Selective inhibition of phosphodiesterase 10A impairs appetitive and aversive conditioning and incentive salience attribution.
The pharmacological effect of the selective PDE10A inhibitor 2-[4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-phenoxymethyl]-quinoline succinic acid (MP-10) on aversively and appetitively motivated behavior in C57BL/6J mice was examined. MP-10 dose-dependently impaired performance on a highly demanding reward schedule during appetitive conditioning. The compound further affected cue-based, but not contextual aversive conditioning. Finally, dose-dependent impaired performance in an instrumentally conditioned reinforcement (ICR) task was found. This suggests that the observed behavioral effects of MP-10 can be at least partially ascribed to impaired incentive salience attribution. MP-10 administration dose-dependently enhanced striatal expression of the immediate early gene Zif268, which suggest that MP-10 affects the studied motivated behaviors by enhancing PDE10A-regulated striatal signaling. Striatal signaling thus appears to be crucial in processes that control reward-motivated behavior in general, and incentive salience attribution in particular. Continued research will prove valuable towards a better understanding of psychopathologies that affect reward-motivated behaviors, such as drug addiction and schizophrenia.


Isolation of guinea pig basophils using anti-leukocyte antibody and density gradient centrifugation on Percoll.
Peripheral blood basophils were isolated from guinea pigs using a 2-step procedure. Initial enrichment of basophils was achieved by treating leukocyte preparations obtained from whole blood with antibody to contaminating granulocytes and mononuclear cells. Basophil populations of 82% purity (mean; range 65-99%) were obtained by subsequent application of the antibody treated preparation to discontinuous Percoll gradients. The isolated basophils were viable and shown to be functional by histamine release upon stimulation with various secretogogues.


Discrimination of small sugar concentration differences helps the nectar-feeding bat Leptonycteris yerbabuenae cover energetic demands.
Every day nectar-feeding animals face an energetic challenge during foraging: they must locate and select flowers that provide nectar with adequate amounts of sugar to cover their very high energy needs. To understand this decision-making process, it is crucial to know how accurately sugar concentration differences can be discriminated. In a controlled laboratory setting, we offered the nectar-specialist bat Leptonycteris yerbabuenae the choice between different sugar solutions covering the entire concentration range of bat-pollinated plants (3-33%). When feeding on solutions below 10% sugar concentration, L. yerbabuenae were unable to cover their energetic demands because of physiological constraints. Their ability to discriminate sugar concentrations was better than that of any other nectar-feeding animal studied to date. At sugar concentrations below 15%, L. yerbabuenae can discriminate solutions differing by only 0.5%. The bats may utilize this fine-tuned ability to select nectar from flowers with reward qualities that provide them with the necessary amount of energy to survive.


Interference of propofol with signal transducer and activator of transcription 5 activation and cardioprotection by remote ischemic preconditioning during coronary artery bypass grafting.
Remote ischemic preconditioning protects the myocardium from ischemia/reperfusion injury. We recently identified protection by remote ischemic preconditioning to be associated with the activation of signal transducer and activator of transcription 5 in left ventricular biopsy specimens of patients undergoing coronary artery bypass grafting during isoflurane anesthesia. Because remote ischemic preconditioning did not protect the heart during propofol anesthesia, we hypothesized that propofol anesthesia interferes with signal transducer and activator of transcription 5 activation. In a randomized, single-blind, placebo-controlled, prospective study, we analyzed an array of established cardioprotective proteins during propofol anesthesia with or without remote ischemic preconditioning in 24 nondiabetic patients with 3-vessel coronary artery disease. Remote ischemic preconditioning (n = 12) compared with no remote ischemic preconditioning (n = 12) failed to decrease the area under the troponin I time curve (273 ± 184 ng/mL × 72 hours vs 365 ± 301 ng/mL × 72 hours; P = .374). Although phosphorylation of several protein kinases was increased from baseline to reperfusion, signal transducer and activator of transcription 5 phosphorylation was not increased and was not different between the remote ischemic preconditioning and no remote ischemic preconditioning groups. Remote ischemic preconditioning during propofol anesthesia did not evoke either signal transducer and activator of transcription 5 activation or cardioprotection, implying interaction of propofol with cardioprotective signaling upstream of signal transducer and activator of transcription 5.