Long-term radiological findings after endonasal endoscopic approach to the skull base.
To study the long-term radiological findings after endonasal endoscopic approach to the skull base. Prospective study that included 55 patients who underwent advance endoscopic skull base surgery. All patients were evaluated with MRI before, 3 months and 12 months after surgery. We used the Lund-Mackay staging system for chronic rhinosinusitis to evaluate the paranasal cavities and the sinonasal scoring system to assess sinonasal symptoms. Seventeen patients (30.9%) underwent extended endonasal approach that required a nasoseptal flap (NSF) for reconstruction of skull base. At baseline the mean total Lund-Mackay score was 0.63 ± 1.2 (range 0-4), and at 3 and 12 months postoperatively the mean scores were 3.5 ± 3.8 (range 0-14) and 2.0 ± 2.5 (range 0-8) respectively. Patients who needed an NSF for reconstruction had a greater Lund-Mackay score (p<0.05). Moreover, NSF is correlated with sinonasal mucosal thickening and fluid retention at 3 months (r=0.45, p<0.01) and 12 months (r=0.4, p<0.01). Total 5-symptom score (T5SS) was similar between both groups at baseline. Patients with extended endoscopic approach reported more smell loss (40.1 ± 26.2; p<0.05) and posterior nasal discharge (49.3 ± 30.1; p<0.05) than TTEA patients (21.6 ± 30.9 and 22.5 ± 27.5 respectively). We observed that sinus opacity is still present after one year of advance endoscopic skull base surgery but symptoms seems to return to basal after 12 months of follow-up.


Microfluidic techniques for enhancing biofuel and biorefinery industry based on microalgae.
This review presents a critical assessment of emerging microfluidic technologies for the application on biological productions of biofuels and other chemicals from microalgae. Comparisons of cell culture designs for the screening of microalgae strains and growth conditions are provided with three categories: mechanical traps, droplets, or microchambers. Emerging technologies for the in situ characterization of microalgae features and metabolites are also presented and evaluated. Biomass and secondary metabolite productivities obtained at microscale are compared with the values obtained at bulk scale to assess the feasibility of optimizing large-scale operations using microfluidic platforms. The recent studies in microsystems for microalgae pretreatment, fractionation and extraction of metabolites are also reviewed. Finally, comments toward future developments (high-pressure/-temperature process; solvent-resistant devices; omics analysis, including genome/epigenome, proteome, and metabolome; biofilm reactors) of microfluidic techniques for microalgae applications are provided.


Nucleotide sequence of the first exon of the rat c-myc gene: proviral insertions in murine leukemia virus-induced lymphomas do not affect exon 1.
We have previously reported that proviruses are integrated adjacent to the c-myc gene in rat thymomas induced by murine leukemia viruses. In order to characterize these insertions, we have isolated recombinant DNA clones from normal rat DNA containing all of the normal rat c-myc gene, and from two Moloney murine leukemia virus-induced lymphomas containing both proviral and adjacent rat c-myc sequences. We determined the DNA sequence of portions of the normal and one tumor-derived clone. The normal and tumor-derived exon 1 sequences are identical. By comparing our sequence to the sequences of mouse and human c-myc, we located the first exon of the rat c-myc gene. Analysis of the tumor-derived rat c-myc clones showed that proviral integration occurred approximately 1.4 kb upstream of exon 1 of c-myc in the case of one tumor and 0.55 kb upstream of c-myc exon 1 in the other. Thus, we conclude that the proviral insertions in these tumors did not affect the rat c-myc gene by altering the structure of the c-myc RNA. Consistent with this, the c-myc RNA present in a cell line derived from one of these tumors is identical in size to the normal c-myc RNA. Furthermore, the level of c-myc expression is not dramatically elevated in this cell line. Exon 1 of the rat c-myc gene contains no ATG start codons and contains multiple stop codons in all three reading frames, indicating that it, like the chicken and mouse exon 1 sequences, is noncoding. The extent of homology between our sequence of rat c-myc exon 1 and the published sequence of human c-myc exon 1 is similar to the extent of homology between the sequences of mouse and human c-myc exon 1. The rat and mouse c-myc exon 1 sequences differ from each other by about the amount predicted from the known divergence times of mice from rats. Exon 1 of c-myc is only slightly conserved, evolving at a rate similar to that seen for introns and pseudogenes.


Inhibition of serine/arginine-rich protein kinase-1 (SRPK1) prevents cholangiocarcinoma cells induced angiogenesis.
The serine/arginine-rich protein kinase-1 (SRPK1) is an enzyme that has an essential role in regulating numerous aspects of mRNA splicing. SRPK1 has been reported to be overexpressed in multiple cancers, suggesting it as a promising therapeutic target in oncology. No previous studies reported the role of SRPK1 in cholangiocarcinoma (CCA) cells. This study aimed to examine the expression of SRPK1 and the effects of SRPK1 inhibition on the viability and angiogenesis activity of CCA cells using a selective SRPK1 inhibitor, SPHINX31. Here, we demonstrate that SPHINX31 (0.3-10 μM) had no inhibitory effects on CCA cells' viability and proliferation. However, SPHINX31 decreased the mRNA expression of pro-angiogenic VEGF-A165a isoform. In addition, SPHINX31 attenuated SRSF1 phosphorylation and nuclear localization, and increased the ratio of VEGF-A165b/total VEGF-A proteins. Moreover, when HUVECs were grown in conditioned medium from SPHINX31-treated CCA cells, migration slowed, and tube formation decreased. The present study demonstrates that targeting SRPK1 in CCA cells effectively attenuates angiogenesis by suppressing pro-angiogenic VEGF-A isoform splicing. These findings suggest a potential therapeutic treatment using SRPK1 inhibitors for the inhibition of angiogenesis in cholangiocarcinoma.


Anticancer molecule AS1411 exhibits low nanomolar antiviral activity against HIV-1.
During clinical trials, a number of fully characterized molecules are dropped along the way because they do not provide enough benefit for the patient. Some of them show limited side effects and might be of great use for other applications. AS1411 is a nucleolin-targeting aptamer that underwent phase II clinical trials as anticancer agent. Here, we show that AS1411 exhibits extremely potent antiviral activity and is therefore an attractive new lead as anti-HIV agent.


Atazanavir.
Atazanavir is a novel azapeptide protease inhibitor with high specificity for, and activity against, HIV-1 protease. The resistance profile of atazanavir is distinct, with an I50 L protease substitution appearing to be the signature mutation. Atazanavir was not associated with increases in total cholesterol, low density lipoprotein-cholesterol or triglyceride levels after 108 weeks. Atazanavir has a pharmacokinetic profile that allows for once-daily oral administration. It is a moderate inhibitor of hepatic cytochrome P450 enzymes and interacts with several drugs. In combination with stavudine plus didanosine, atazanavir 200, 400 or 500 mg once daily produced a rapid and sustained reduction from baseline in viral load of 2.57, 2.42 and 2.53 log(10) copies/mL, respectively, in treatment-naive patients after 48 weeks, compared with a decrease of 2.33 log(10) copies/mL with nelfinavir 750 mg three times daily. Nausea was the most clinically relevant adverse event reported in patients receiving atazanavir-based regimens.


Degradation of Acetaminophen via UVA-induced advanced oxidation processes (AOPs). Involvement of different radical species: HO, SO4- and HO2/O2.
In this work, UVA radiation that is part of solar light is taken as the irradiation source and radicals (HO, SO4- and HO2/O2-) are generated through activation of hydrogen peroxide (H2O2), sodium persulfate (Na2S2O8) and Bismuth catalyst (BiOCl), respectively. The distinguished performance in removing acetaminophen (ACTP), a model pharmaceutical pollutant, by these three radicals was compared for the first time. Effect of pH, halide ions concentration and interfacial mechanism have been investigated in detail. Interestingly, results show that heterogeneous UVA/BiOCl process has higher degradation efficiency than homogeneous UVA/H2O2 and UVA/Na2S2O8 systems whatever the solution's pH. To explain these results, second order reaction rate constant (kradical, ACTP) have been determined with laser flash photolysis (LFP) or radical scavenging experiments. The strongly interfacial-depended HO2/O2- radicals have the lowest second order rate constant with ACTP but highest steady state concentration. BiOCl is much easier activated by UVA, and outstanding ACTP mineralization can be achieved. Combination of BiOCl and Na2S2O8 exhibits synergistic effects rather than antagonism effects with H2O2. This study highlights the relative effective utilization of solar light through interfacial directed BiOCl photocatalysis and its synergistic effects with traditional oxidants.


The radiological diagnosis of posttraumatic effusion of the elbow joint and its clinical significance: the 'displaced fat pad' sign.
Alterations occur in the radiological appearance of the soft tissues after injury to the elbow joint. These are due to displacement of the intra-articular fat pads by capsular distension when an effusion is present. A prospective study of 89 consecutive elbow injuries was undertaken in an attempt to assess the usefulness and reliability of these changes in the diagnosis of minor elbow injuries and the assessment of their clinical progress. In 61 elbows (69 per cent) there was no radiological evidence of an effusion and no evidence of bony injury. All quickly returned to normal. In 28 elbows (31 per cent) radiological evidence of an effusion was present. Twenty-three (80 per cent) of these were also found to have a fracture in, or adjacent to the elbow joint. In 9 elbows the fracture could not be seen on the initial radiographs. Because of the presence of an effusion, repeat radiographs were taken and a fracture discovered. The presence of an effusion was associated with an increase in the time required for full recovery.


The epidemiology of diabetes in childhood with special reference to the Orient: implications for mechanism of beta cell damage.
Epidemiologic studies are providing important new insights into the etiology and clinical course of IDDM as well as providing critically needed data on the magnitude of the problem in different parts of the world. The development of national IDDM registries have documented extraordinary differences in diabetes incidence and prevalence, with the highest incidence figures in Finland (greater than 30/100,000/yr) and the lowest in the Orient with Korea reporting incidence rates below 1 and Japan between 1.0-2.4/100,000/yr. The great geographic variation in expression of diabetes in childhood is strongly supportive of environmental factors playing a major role in the etiology of disease. Our studies document a linear correlation between IDDM incidence and distance from the equator and a similar but inverse correlation with mean annual environmental temperature. Other workers find a direct correlation with dairy product consumption. Factors that may play a role in beta cell damage include viral infections, environmental toxins, nutrients and stress factors. Because of the low incidence of IDDM among children living in Asia it is most important to expand the current national registries in the Asian countries and begin a careful study of the environmental differences within Asian countries as well as comparison of studies between countries with very high incidence rates and those with the lowest rates.


The taxonomy of Penicillium species from fermented cheeses.
The taxonomy of the Penicillium camberti and P. roqueforti series is re-investigated. P. caseicolum Bainier is regarded as a synonym of P. camemberti Thom on the basis of morphological characters. P. casei Staub is considered to be identical with P. verrucosm Dierckx var. cyclopium (Westling) Samson, Stolk et Hadlok. Descriptions and illustrations of P. camemberti and P. roqueforti Thom are given. The occurrence and mycotoxin production of both species are shortly discussed.


A Validated Prediction Model for Overall Survival From Stage III Non-Small Cell Lung Cancer: Toward Survival Prediction for Individual Patients.
Although patients with stage III non-small cell lung cancer (NSCLC) are homogeneous according to the TNM staging system, they form a heterogeneous group, which is reflected in the survival outcome. The increasing amount of information for an individual patient and the growing number of treatment options facilitate personalized treatment, but they also complicate treatment decision making. Decision support systems (DSS), which provide individualized prognostic information, can overcome this but are currently lacking. A DSS for stage III NSCLC requires the development and integration of multiple models. The current study takes the first step in this process by developing and validating a model that can provide physicians with a survival probability for an individual NSCLC patient. Data from 548 patients with stage III NSCLC were available to enable the development of a prediction model, using stratified Cox regression. Variables were selected by using a bootstrap procedure. Performance of the model was expressed as the c statistic, assessed internally and on 2 external data sets (n=174 and n=130). The final multivariate model, stratified for treatment, consisted of age, gender, World Health Organization performance status, overall treatment time, equivalent radiation dose, number of positive lymph node stations, and gross tumor volume. The bootstrapped c statistic was 0.62. The model could identify risk groups in external data sets. Nomograms were constructed to predict an individual patient's survival probability (www.predictcancer.org). The data set can be downloaded at https://www.cancerdata.org/10.1016/j.ijrobp.2015.02.048. The prediction model for overall survival of patients with stage III NSCLC highlights the importance of combining patient, clinical, and treatment variables. Nomograms were developed and validated. This tool could be used as a first building block for a decision support system.


Oral prednisone taper following intravenous steroids fails to improve disability or recovery from relapses in multiple sclerosis.
A short course of intravenous methylprednisolone (IVMP) followed by oral prednisone taper (OPT) is often used for the treatment of relapses in multiple sclerosis (MS). We examined the effect of IVMP plus OPT compared with IVMP only on neurologic disability 1 year after treatment of a relapse in patients with relapsing-remitting multiple sclerosis. Two hundred eighty-five consecutive relapses were analyzed in a retrospective fashion. One hundred fifty-two patients with a total of 171 relapses received IVMP plus an OPT at the time of relapse whilst 112 patients who experienced 114 relapses received IVMP without OPT. There was no difference between the two groups in the baseline characteristics as well as the mean or categorical EDSS at baseline, at the time of relapse confirmation, and at months 3, 6 and 12 after relapse confirmation. Our observations suggest that OPT following treatment with IVMP for an MS relapse does not lead to improved neurologic outcome after 12 months compared with treatment with IVMP only. Moreover, our findings raise concerns regarding the common practice of using OPT following IVMP. Further studies are indicated to validate our findings and minimize exposure to systemic corticosteroids, well known for systemic toxicity.


[Health planning and management, instruments for technical cooperation].
Western models of health strategy are not applicable in developing countries. These need, for developing original and effective health services and systems, a planning method meeting their specific requirements. A WHO-sponsored collaborative development effort from 1970 to this day resulted in a set of programming, project formulation and management procedures broadly based on the systems approach. The 31st World Health Assembly commended this effort, which is on-going.


Mechanical properties and machinability of lithium silicate glass-ceramics with varying MgO content.
This study focused on the role of lithium metasilicate crystalline phase and microstructural evolution on altering the mechanical properties and machinability of two glass-ceramic system, (Li2O-K2O-Na2O-CaO-MgO-ZrO2-Al2O3-P2O5-SiO2), previously developed by our research group. Our previous study showed that increasing MgO content introduced phase separation and thus controlling the crystallization and microstructure of the glass-ceramics. For this study we chose the glass ceramic system with 1.5 and 4.5 mol% MgO. The glass-ceramics were prepared by melt cast method followed by heat treatment at 650 °C to induce partial crystallization. The crystalline phase in the glass-ceramics was identified by x-ray diffraction and the quantification of crystalline and amorphous phase content was done using Rietveld refinement. The hardness and elastic moduli were measured by nanoindentation. Vickers hardness and fracture toughness were determined by micro indentation. Nano scratch test was performed and scratch morphology was characterized using AFM and FEG-SEM. In order to compare the machinability of the prepared glass-ceramic samples, milling experiments were carried out using CNC milling machine, and machining characteristics were compared by analysing machining force, surface roughness and microstructure of the machined surface. Presence of higher amount of lithium metasilicate (LS) crystals in higher magnesia containing glass-ceramic (G2) resulted in lower average force (Fyrms) as compared to lower MgO containing glass-ceramic. However, due to a wide range of variation in crystal size (150 nm - 2 μm) in higher MgO containing glass-ceramic, the force fluctuation was more than lower MgO containing glass-ceramics.


Variations in 10-month-old infant imitation of people and things.
To explore 10-month-old infants' abilities to engage in intentional imitation, they were shown a human agent, a non-human agent (stuffed animal), and a surrogate object (mechanical pincers) model actions on objects. The tendency of infants to perform the target act was compared in several situations: (a) after test items were manipulated but the target action was not shown, (b) after the target act was demonstrated successfully, and (c) after the target act was demonstrated unsuccessfully. Although infants imitated the successful actions of human and non-human agents, they completed the unsuccessful actions of humans only. Toward the surrogate object infants did not respond differentially. These findings suggest that although infant may mimic the actions of human and non-human agents, they only engage in intentional imitation with people.


Upper Instrumented Vertebrae, Number of Levels Fused, and Plate Morphology Do Not Affect Severity of Chronic Dysphagia After Anterior Cervical Spine Surgery.
Disordered swallowing, or dysphagia, is the most common complication after anterior cervical spine (ACS) surgery. Many operative factors are associated with development of dysphagia. The aim of this study was to explore how number of levels instrumented, specific levels fused, and plate morphology affect chronic dysphagia after ACS surgery. Consecutive patients referred to a tertiary center for otolaryngology evaluation for chronic dysphagia after ACS surgery between 2012 and 2017 were enrolled. Basic demographic data were obtained. Plain radiographs were reviewed for number of levels fused, upper instrumented vertebrae, and plate morphology. Plate morphology was categorized as a closed, small window, large window, or no profile plate. The 10-item Eating Assessment Tool (EAT-10) was used to assess dysphagia severity. Of 171 patients referred for dysphagia, 126 met inclusion criteria; 54% were female, with a mean age of 63 years (range, 32-88 years). Mean EAT-10 score was 18.5 ± 10.1. Mean time from spine surgery to videofluoroscopic swallow study for dysphagia was 58.3 months. Mean number of levels fused was 2.2 ± 0.9. There were no significant differences in EAT-10 scores in single-level versus multilevel fusion (19.0 vs. 18.4, P = 0.76) as well as with regard to upper instrumented vertebrae or plate morphology. In this series of patients with chronic dysphagia following ACS surgery, the severity of dysphagia as measured by the EAT-10 was not affected by upper instrumented vertebrae, number of levels fused, or plate morphology.


External Validation of the RETREAT Score for Prediction of Hepatocellular Carcinoma Recurrence after Liver Transplantation.
We aimed to externally validate the performance of the RETREAT score in a European population. This single center retrospective cohort study enrolled all consecutive patients with HCC who underwent LT between 1989 and 2019. The performance of RETREAT was assessed in the overall population and after stratification between being within or beyond the Milan criteria based on the explant pathology report. Recurrence probabilities were estimated by using the Kaplan-Meier method and compared by log-rank test. We studied 203 patients; 42 patients were beyond the Milan criteria based on explant pathology. The median follow-up was 26.8 months (IQR 7.2-60.7). Overall cumulative HCC recurrence rates were 10.6%, 21.3%, and 23.0% at 2, 5, and 10 years, with the majority of recurrences extrahepatic and at multiple sites. Higher RETREAT scores were associated with higher recurrence rates, with a 10-year recurrence rate of 60.5% in patients with RETREAT ≥ 3 (n = 65), compared to 6.2% in those with RETREAT ≤2 (n = 138; p < 0.001). HCC recurrence rates were even lower in patients within the Milan criteria who also had a low RETREAT score (n = 122; 2.7% at 10 years). Low RETREAT scores identify patients at low risk of HCC recurrence after LT in patients within the Milan criteria based on explant pathology.


Localization and neuronal response of RFamide related peptides in the rat central nervous system.
RFamide related peptides (RFRP)-1 and RFRP-3 are neuropeptides derived from the same preproprotein. We have examined the distribution of RFRP-1 and RFRP-3 immunoreactivities (irs) in the rat central nervous system using specific antibodies. Neuronal cell bodies containing both RFRP-1 and RFRP-3 were detected within the caudal portion of the hypothalamus, the periventricular nucleus (PerVN), and the portion around or above the ventromedial nucleus of the hypothalamus. Both immunohistochemical and in situ hybridization analyses showed that neurons containing RFRP immunoreactivity and mRNA were distinct from those of neuropeptide FF, which contains the same structure at the C-terminus, Pro-Glu-Arg-Phe-NH2, as RFRP-3. Fibers containing both RFRP-1 and RFRP-3 were widely distributed in the brain: the lateral septal nucleus in the telencephalon, the paraventricular thalamic nucleus, various hypothalamic nuclei, the periaqueductal gray in the midbrain, the parabrachial nucleus in the pons, and the nucleus tractus solitarius (NTS) in the medulla oblongata. Only RFRP-1-ir was detected within the posterior gray horn in the spinal cord. Only RFRP-3-ir was detected in several thalamic nuclei and the spinal cord, especially at the posterior intermediate sulcus and within the anterior gray horn. Intracerebroventricular administration of RFRPs induced c-Fos expression in the anterior portion of the NTS, locus coeruleus, the nucleus of incertus, supraoptic nucleus, PerVN and the arcuate nucleus of the hypothalamus. These results show that RFRP-1 and RFRP-3 are widely distributed in the rat central nervous system and might be involved in various functions such as the neuroendocrine system or pain modulation.


Polyinosinic acid induces TNF and NO production as well as NF-kappaB and AP-1 transcriptional activation in the monocytemacrophage cell line RAW 264.7.
This study evaluates the poly inosinic acid (poly I)-induced activation in the murine monocytemacrophage cell line RAW 264.7, which led to an inflammatory phenotype. RAW 264.7, and WEHI 164 cell lines were used. The activation process is characterized by the acquisition of a mature macrophage morphology and the production of inflammatory mediators tumor necrosis factor (TNF) and nitric oxide (NO). The activation by poly I has distinctive features. Thus, poly I induced an increase in nuclear factor kappaB (NF-kappaB) transcriptional activity due to a long-term degradation of inhibitory NF-kappaB (IkappaB) beta while lipopolysaccharide (LPS) induced the degradation of both IkappaBalpha and IkappaBbeta. Poly I also induced an increase in activator protein 1 (AP-1) transcriptional activity, possibly due to the activation of the mitogen activated protein kinases (MAPKs) ERK, Jun N terminal kinase (JNK) and p38. Dextran sulphate (DS) efficiently inhibited the activation induced by poly I including the production of the inflammatory mediators. Dextran sulphate also inhibited AP-1 and NF-kappaB transcriptional activities in poly I-stimulated cells. RAW 264.7 cells express macrophage scavenger receptor 1 (Msr1) type I and Msr1 type II that are differently up-regulated upon treatment with poly I. The results presented demonstrate that the well-known blocker of scavenger receptors poly I activates macrophages to produce TNF and NO, triggering specific signal transduction pathways.


Association of HLA diversity with the risk of 25 cancers in the UK Biobank.
The human leukocyte antigen (HLA) is a highly polymorphic region, and HLA diversity may play a role in presenting tumour-associated peptides and inducing immune responses. However, the effect of HLA diversity on cancers has not been fully assessed. We aimed to explore the role of HLA diversity on cancer development. A pan-cancer analysis was performed to evaluate the effect of HLA diversity, measured by HLA heterozygosity and HLA evolutionary divergence (HED), on the susceptibility of 25 cancers in the UK Biobank. We observed that the diversity of HLA class II locus was associated with a lower risk of lung cancer (ORhetero = 0.94, 95% CI = 0.90-0.97, P = 1.29 × 10-4) and head and neck cancer (ORhetero = 0.91, 95% CI = 0.86-0.96, P = 1.56 × 10-3). Besides, a lower risk of non-Hodgkin lymphoma was associated with an increased diversity of HLA class I (ORhetero = 0.92, 95% CI = 0.87-0.98, P = 8.38 × 10-3) and class II locus (ORhetero = 0.89, 95% CI = 0.86-0.92, P = 1.65 × 10-10). A lower risk of Hodgkin lymphoma was associated with the HLA class I diversity (ORhetero = 0.85, 95% CI = 0.75-0.96, P = 0.011). The protective effect of HLA diversity was mainly observed in pathological subtypes with higher tumour mutation burden, such as lung squamous cell carcinoma (P = 9.39 × 10-3) and diffuse large B cell lymphoma (Pclass I = 4.12 × 10-4; Pclass Ⅱ = 4.71 × 10-5), as well as the smoking subgroups of lung cancer (P = 7.45 × 10-5) and head and neck cancer (P = 4.55 × 10-3). We provided a systematic insight into the effect of HLA diversity on cancers, which might help to understand the etiological role of HLA on cancer development. This study was supported by grants from the National Natural Science Foundation of China (82273705, 82003520); the Basic and Applied Basic Research Foundation of Guangdong Province, China (2021B1515420007); the Science and Technology Planning Project of Guangzhou, China (201804020094); Sino-Sweden Joint Research Programme (81861138006); the National Natural Science Foundation of China (81973131, 81903395, 81803319, 81802708).


Isolation, structure elucidation and neuroprotective effects of caffeoylquinic acid derivatives from the roots of Arctium lappa L.
Five undescribed caffeoylquinic acid derivatives (CQAs), along with fifteen known CQAs, were isolated from the roots of Arctium lappa L.(burdock). The chemical structures of compounds were determined using extensive spectroscopic analyses, including UV, IR, NMR and MS. Further in vitro bioactive investigation demonstrated the neuroprotective effects of these compounds against the neurotoxicity of hydrogen peroxide (H2O2) and N-methyl-D-aspartate (NMDA). 1,3,5-tri-O-caffeoylquinic acid and 1,4,5-tri-O-caffeoylquinic acid significantly reduced H2O2-induced human neuroblastoma SH-SY5Y cell death with concentration for 50% of maximal effect (EC50) values of 17.3 and 19.3 μM. Meanwhile, 3,5-di-O-caffeoyl-1-O-maloylquinic acid displayed protective effect against NMDA-induced cell injury with EC50 values of 18.4 μM. Overall, the more caffeoyl, the better the antioxidant activity, while the maloyl-containing compounds had better anti-NMDA activity.


Environmental release of dioxins from reservoir sources during beach nourishment programs.
In late 1990s, USEPA/FDA made an important connection regarding the presence of elevated levels of dioxins (e.g., 1500 ng kg(-1) TEQ) in ball clays mined in Mississippi (USA) from a geological deposit dated to ~40 million years (Mississippi Embayment) that stretches over several states (northern part of Mississippi to Kentucky) and levels of dioxins in selected animal food sources. Following a recent beach nourishment program along the mid-Atlantic coast of the US, a number of dark gray, blue tinted nuggets of varying sizes were found on beach strands and near the shoreline. Using the presence of these balls of clay (shape, color, and knowledge regarding their use in pottery) on the beach, together with our direct experience analyzing ball clays for dioxins, we made a possible association between these clays and elevated dioxins. Concerns regarding the potential of nourishment programs to cause severe damage to our beaches drove us to test the dioxin content of nourishment exposed clays. A number of the nuggets, along with freshly dredged and deposited sand (collected the morning after nourishment) with the same coloration, and others (sun-bleached), collected approximately 2 weeks after the completion of the nourishment efforts, were analyzed for the presence of PCDD/Fs, PCBs, and selected semi-volatile chlorinated organics. The clay PCDD/F WHO2005-TEQs (dry weight; ND=DL; EMPC=EMPC) ranged from 0.41 to 5.78 ng kg(-1) with an average of 2.64 ng kg(-1), whereas the sand sample's TEQs ranged from 0.18 to 0.31 ng kg(-1) PCDD/F WHO-2005, with an average of 0.22 ng kg(-1). The average total tetra- through octachlorinated dibenzo-p-dioxin concentration was 2700 ng kg(-1) (with a maximum of 5800 ng kg(-1)) for the clays and 8.5 ng kg(-1) (with a maximum of 16.8 ng kg(-1)) for the sand samples. The congener 2,3,7,8-TCDD (TEF=1) was detected in half of the clay samples (0.11-0.77 ng kg(-1)). All of the clay and sand samples displayed an unambiguous and dominating 1,4,6,9-chlorination pattern across homolog groups. No other chlorinated aromatics were detected above background levels. The observations, along with the absence or an extremely low level of polychlorinated dibenzofurans, together with the mineralogical analysis, supports the conclusion that off-shore dredging activities are reaching reservoir sources containing dioxin-tainted, smectic/kaolinite clay minerals. Subsequent beach erosion provides additional environmental releases over time, as buried balls of clay from previous nourishment efforts become exposed.


Biomechanical evaluation of the thoracolumbar spine comparing healthy and irregular thoracic and lumbar curvatures.
The geometric alignment of the spine plays an integral role in stability, biomechanical loading, and consequently, pain, and a range of healthy sagittal curvatures has been identified. Spinal biomechanics when sagittal curvature is outside the optimal range remains a debate and may provide insight into the load distribution throughout the spinal column. A thoracolumbar spine model (Healthy) was developed. Thoracic and lumbar curvatures were adjusted by 50% to create models with varying sagittal profiles: hypolordotic (HypoL), hyperlordotic (HyperL), hypokyphotic (HypoK), and hyperkyphotic (HyperK). In addition, lumbar spine models were constructed for the former three profiles. The models were subjected to loading conditions simulating flexion and extension. Following validation, intervertebral disc stresses, vertebral body stresses, disc heights, and intersegmental rotations were compared across all models. Overall trends demonstrated that HyperL and HyperK models had a noticeable reduction in disc height and greater vertebral body stresses compared to the Healthy model. In comparison, the HypoL and HypoK models displayed opposite trends. Considering the lumbar models, the HypoL model had reduced disc stresses and flexibility, while the contrary was observed in the HyperL model. Results indicate that the models with excessive curvature may be subjected to greater stress magnitudes, while the straighter spine models may reduce these stresses. Finite element modeling of spine biomechanics demonstrated that variations in sagittal profiles influence the load distribution and range of motion of the spine. Considering patient-specific sagittal profiles in finite element modeling may provide valuable insight for biomechanical analyses and targeted treatments.


Assaying Cyclin-Dependent Kinase Activity in Synchronized Algal Cultures.
Cyclin-dependent kinases (CDKs) are key regulators of the cell cycle in eukaryotes. Assessing their activity is one of the basic methods used to analyze their function. This is particularly true in synchronized cultures of unicellular organisms, where the entire culture is in the same physiological state. In this chapter, I describe a simple biochemical method to assess CDK activity in algae. Although the results are easier to interpret in the context of synchronized cultures, the method is not limited to them. The protocol requires only standard laboratory equipment and access to a radioactivity working room. The method is applicable to any algal species, including newly developed ones, as it does not require any specific tools. The method can, therefore, be used to widen the portfolio of cell cycle regulatory models within algae.


Improving the effectiveness of three essential oils against Aedes aegypti (Linn.) and Anopheles dirus (Peyton and Harrison).
Repellency of essential oil extracted from Curcuma longa, Eucalyptus globulus, and Citrus aurantium at various concentrations (5, 10, 15, 20, and 25 %) with and without 5 % vanillin was evaluated against female mosquitoes: Aedes aegypti and Anopheles dirus. The comparisons were made with a commercial chemical repellent (N,N-diethyl-3-methylbenzamide (DEET) 25 % w/w; KOR YOR 15) by arm in cage method. It was found that the essential oils with 5 % vanillin gave the longest lasting period against two mosquitoes as follows: Curcuma longa gave 150 min for Ae. aegypti, 480 min for An. dirus; Eucalyptus globulus gave 144 min for Ae. aegypti, 390 min for An. dirus; and Citrus aurantium gave 120 min for Ae. aegypti, 360 min for An. dirus. The 25 % Curcuma longa essential oil exhibited the best efficiency as equal as a commercial repellent (480 min against An. dirus). Vanillin can extend the period of time in protection against the two mosquitoes. This study indicates the potential uses of the essential oils (Curcuma longa, Eucalyptus globulus, and Citrus aurantium) with vanillin as natural mosquito repellents.


Internally simulated movement sensations during motor imagery activate cortical motor areas and the cerebellum.
It has been proposed that motor imagery contains an element of sensory experiences (kinesthetic sensations), which is a substitute for the sensory feedback that would normally arise from the overt action. No evidence has been provided about whether kinesthetic sensation is centrally simulated during motor imagery. We psychophysically tested whether motor imagery of palmar flexion or dorsiflexion of the right wrist would influence the sensation of illusory palmar flexion elicited by tendon vibration. We also tested whether motor imagery of wrist movement shared the same neural substrates involving the illusory sensation elicited by the peripheral stimuli. Regional cerebral blood flow was measured with H215O and positron emission tomography in 10 right-handed subjects. The right tendon of the wrist extensor was vibrated at 83 Hz ("illusion") or at 12.5 Hz with no illusion ("vibration"). Subjects imagined doing wrist movements of alternating palmar and dorsiflexion at the same speed with the experienced illusory movements ("imagery"). A "rest" condition with eyes closed was included. We identified common active fields between the contrasts of imagery versus rest and illusion versus vibration. Motor imagery of palmar flexion psychophysically enhanced the experienced illusory angles of plamar flexion, whereas dorsiflexion imagery reduced it in the absence of overt movement. Motor imagery and the illusory sensation commonly activated the contralateral cingulate motor areas, supplementary motor area, dorsal premotor cortex, and ipsilateral cerebellum. We conclude that kinesthetic sensation associated with imagined movement is internally simulated during motor imagery by recruiting multiple motor areas.


Label-free detection of aflatoxin M1 with electrochemical Fe3O4/polyaniline-based aptasensor.
The selective detection of ultratrace amounts of aflatoxin M1 (AFM1) is extremely important for food safety since it is the most toxic mycotoxin class that is allowed to be present on cow milk with strictly low regulatory levels. In this work, Fe3O4 incorporated polyaniline (Fe3O4/PANi) film has been polymerized on interdigitated electrode (IDE) as sensitive film for AFM1 electrochemical biosensor. The immobilized aptamers as an affinity capture reagent and magnetic nanoparticles for signal amplification element have been employed in the sensing platform. Label-free and direct detection of the aptamer-AFM1 on Fe3O4/PANi interface were performed via electrochemical signal change, acquired by cyclic and square wave voltammetries. With a simplified strategy, this electrochemical aptasensor shows a good sensitivity to AFM1 in the range of 6-60 ng·L(-1), with the detection limit of 1.98 ng·L(-1). The results open up the path for designing cost effective aptasensors for other biomedical applications.


In vitro studies of gallstone dissolution using bile salt solutions and heparinized saline.
A controlled in vitro study of gallstone dissolution has been carried out using a model designed to simulate the in vivo situation in the bile ducts. Sodium taurocholate, sodium cholate, heparinized saline and physiological saline were infused for 10 days over 81 stones from 32 patients and changes in weight and structure were recorded. The bile salt solutions caused weight loss in 81-5 and 85-7 per cent respectively of the stones treated, but the two saline solutions caused weight gains in 74-5 and 88 per cent respectively. Fragmentation occurred in 18-5% of stones treated with sodium taurocholate, in 25% of those treated with sodium cholate and in 11-8 per cent of those treated with heparinized saline. Small stones lost a lower absolute amount of weight than large stones but this represented a greater proportion of their initial weight. These investigations confirm the advantages of a dynamic in vitro model to study gallstone dissolution. Bile salt solutions infused into the bile ducts may clear retained stones by causing reduction in stone weight or fragmentation or both, but heparinized saline appears to be unsuitable for gallstone dissolution. Larger stones may require longer periods of infusion.


Electrophysiological mapping of cat primary auditory cortex with multielectrode arrays.
The present study employs simultaneous multielectrode recording techniques to study the feline primary auditory cortex (AI) to characterize its functional architecture. High electrode-count microelectrode arrays provide a high spatial and temporal view of AI, but at the potential cost of significant cortical insult. However, the number of electrodes that record single- and multiunit action potentials shown in this study suggest that the implantation of high electrode-count microelectrode arrays allows for reliable recordings from the cortex and that the neurons abutting the electrode tips appear to be spared from significant insult. Using these recordings, we have constructed a functional model of AI that best specifies the distribution of characteristic frequencies (CF's), and have reaffirmed that CF is logarithmically distributed across the cortical surface with a principal CF axis perpendicular to generally straight isofrequency contours. In four cats, we found that the average CF gradient was 0.53 +/- 0.08 octave per millimeter. This study demonstrates the use of high electrode count, microelectrode array recordings in characterizing the spatial distribution of acoustic information in the feline AI.


The majority of type 2 diabetic patients in Finnish primary care are at very high risk of cardiovascular events: A cross-sectional chart review study (STONE HF).
To characterize clinical profiles, prevalence of chronic kidney disease (CKD), and treatment patterns in type 2 diabetes (T2D) and heart failure (HF) patients in Finnish primary care. A total of 1385 patients (1196 with T2D, 50 with HF, and 139 with T2D and HF) in 60 Finnish primary care centers were recruited to this cross-sectional study. Data on demographic and clinical characteristics, laboratory measurements, and medications were collected retrospectively from medical records. T2D patients were classified according to their risk of cardiovascular (CV) events as very high-risk (62%) and other patients (38%). Of the T2D patients, 10% (139/1335) had a diagnosis of HF and 42% (457/1090) had stage 3-5 CKD and/or albuminuria based on laboratory measurement. Of the HF patients, 74% (139/189) had T2D and 78% (114/146) had stage 3-5 CKD and/or albuminuria. Metformin was the most frequently used medication in both very high-risk patients (74%) and other patients (86%). SGLT2 inhibitors and/or GLP-1 analogues were used by 37% of very high-risk patients compared to 42% in other patients. The majority of T2D patients in Finnish primary care are at very high risk of cardiovascular events. However, the implementation of treatments with proven cardioprotective effects in very high-risk patients is currently suboptimal.


Results of a diabetic retinopathy screening. Risk markers analysis.
To identify risk markers for retinopathy in patients from our geographic area, and to compare them with those published in other studies. To design a screening interval strategy, taking into account these results, and compare it with intervals suggested in published studies. Cross-sectional observational study on 383 diabetic patients with no previous retinopathy diagnosis, who were screened for diabetic retinopathy. An analysis was made on the possible association between patient factors and presence of retinopathy. A greater probability for finding retinopathy in diabetic patients was associated to insulin treatment in our study, with a statistical significance level of 95%. In patients with less than 10year onset of their diabetes, only mild retinopathy without macular oedema was found. Insulin treatment and time of onset of diabetes should be taken into account when designing efficient screening strategies for diabetic retinopathy.


Time range analysis of evoked potential fields.
Potentials evoked by contrast reversing grating stimuli of different spatial frequency and orientation were recorded in 16 channels from twelve healthy adults. The amount of electrical brain activity was quantified independent of the reference electrode by the computation of global field power (GFP). Maxima of the GFP function over times, determined component latencies which turned out to be influenced by spatial frequency and orientation. Both effects were statistically significant. Analysis of GFP at component latencies demonstrated the significant influence of spatial frequency on the amount of activity in the potential fields, whereas different stimulus orientations yielded brain activity of similar strength. Component location on the scalp determined at P100 latency showed no systematic variation with spatial frequency or orientation of the grating pattern. A reference-free topographic segmentation procedure based on the statistical recognition of stable potential field configurations disregarding amplitude characteristics, was used for all subjects and stimulus conditions. Segments were identified over the whole recording epoch and were interpreted as time epochs with identical potential field configurations, that were compatible with identical neuronal generators. The sequence of such segments was further analysed and compared statistically between subjects and stimulus conditions. The results showed topographical differences that were not observed when only selected time points at component latency were considered.


Adenosine A2A receptors facilitate synaptic NMDA currents in CA1 pyramidal neurons.
NMDA receptors play a key role in both synaptic plasticity and neurodegeneration. Adenosine is an endogenous neuromodulator and through membrane receptors of the A2A subtype can influence both synaptic plasticity and neuronal death. The present work was designed to evaluate the influence of adenosine A2A receptors upon NMDA receptor activity in CA1 hippocampal neurons. We discriminated between modulation of synaptic versus extrasynaptic receptors, since extrasynaptic NMDA receptors are mostly associated with neurodegeneration while synaptic NMDA receptors are linked to plasticity phenomena. Whole-cell patch-clamp recordings were obtained to evaluate NMDA receptor actions on CA1 pyramidal neurons of young adult (5-10 weeks) male Wistar rat hippocampus. Activation of A2A receptors with CGS 21680 (30 nM) consistently facilitated chemically-evoked NMDA receptor-currents (NMDA-PSCs) and afferent-evoked NMDA-currents (NMDA-EPSCs), an action prevented by an A2A receptor antagonist (SCH58261, 100 nM) and a PKA inhibitor, H-89 (1 μM). These actions did not reflect facilitation in glutamate release since there was no change in NMDA-EPSCs paired pulse ratio. A2A receptor actions were lost in the presence of an open-channel NMDA receptor blocker, MK-801 (10 μM), but persisted in the presence of memantine, at a concentration (10 μM) known to preferentially block extrasynaptic NMDA receptors. These results show that A2A receptors exert a positive postsynaptic modulatory effect over synaptic, but not extrasynaptic, NMDA receptors in CA1 neurons and, therefore, under non-pathological conditions may contribute to shift the dual role of NMDA receptors towards enhancement of synaptic plasticity.


Red-tailed hawk algorithm for numerical optimization and real-world problems.
This study suggests a new nature-inspired metaheuristic optimization algorithm called the red-tailed hawk algorithm (RTH). As a predator, the red-tailed hawk has a hunting strategy from detecting the prey until the swoop stage. There are three stages during the hunting process. In the high soaring stage, the red-tailed hawk explores the search space and determines the area with the prey location. In the low soaring stage, the red-tailed moves inside the selected area around the prey to choose the best position for the hunt. Then, the red-tailed swings and hits its target in the stooping and swooping stages. The proposed algorithm mimics the prey-hunting method of the red-tailed hawk for solving real-world optimization problems. The performance of the proposed RTH algorithm has been evaluated on three classes of problems. The first class includes three specific kinds of optimization problems: 22 standard benchmark functions, including unimodal, multimodal, and fixed-dimensional multimodal functions, IEEE Congress on Evolutionary Computation 2020 (CEC2020), and IEEE CEC2022. The proposed algorithm is compared with eight recent algorithms to confirm its contribution to solving these problems. The considered algorithms are Farmland Fertility Optimizer (FO), African Vultures Optimization Algorithm (AVOA), Mountain Gazelle Optimizer (MGO), Gorilla Troops Optimizer (GTO), COOT algorithm, Hunger Games Search (HGS), Aquila Optimizer (AO), and Harris Hawks optimization (HHO). The results are compared regarding the accuracy, robustness, and convergence speed. The second class includes seven real-world engineering problems that will be considered to investigate the RTH performance compared to other published results profoundly. Finally, the proton exchange membrane fuel cell (PEMFC) extraction parameters will be performed to evaluate the algorithm with a complex problem. The proposed algorithm will be compared with several published papers to approve its performance. The ultimate results for each class confirm the ability of the proposed RTH algorithm to provide higher performance for most cases. For the first class, the RTH mostly got the optimal solutions for most functions with faster convergence speed. The RTH provided better performance for the second and third classes when resolving the real word engineering problems or extracting the PEMFC parameters.


Is chemical analysis suitable for detecting mycotoxins in agricultural commodities and foodstuffs?
The assessment of the risks of mycotoxins to humans through consuming contaminated foods resulted in specific legislation that evaluates the presence, quantities, and type of mycotoxins in agricultural commodities and foodstuffs. Thus, to ensure compliance with legislation, food safety and consumer health, the development of suitable analytical procedures for identifying and quantifying mycotoxins in the free or modified form, in low-concentration and in complex samples is necessary. This review reports the application of the modern chemical methods of analysis employed in mycotoxin detection in agricultural commodities and foodstuffs. It is reported extraction methods with reasonable accuracy and those present characteristics according to guidelines of Green Analytical Chemistry. Recent trends in mycotoxins detection using analytical techniques are presented and discussed, evaluating the robustness, precision, accuracy, sensitivity, and selectivity in the detection of different classes of mycotoxins. Sensitivity coming from modern chromatographic techniques allows the detection of very low concentrations of mycotoxins in complex samples. However, it is essential the development of more green, fast and more suitable accuracy extraction methods for mycotoxins, which agricultural commodities producers could use. Despite the high number of research reporting the use of chemically modified voltammetric sensors, mycotoxins detection still has limitations due to the low selectivity from similar chemical structures of mycotoxins. Furthermore, spectroscopic techniques are rarely employed due to the limited number of reference standards for calibration procedures.


Dark and photoreactivity of 4'-aminomethyl-4,5',8-trimethylpsoralen with T7 phage.
The dark and photoreactions of 4'-aminomethyl-4,5',8-trimethylpsoralen (AMT) with T7 phage were investigated from biological and structural points of view. The dark reaction leads to the structural destabilization of the double helix of the DNA as is shown by optical melting measurements. The genotoxicity of AMT in the dark is comparable with that of known genotoxic drugs as determined by phage inactivation. The photoreaction with UVA light leads to the formation of mono- and di-adducts depending on the wavelength and dose used. Mono- and di-adducts influence DNA stability differently; biologically both types of adducts are genotoxic as measured by action spectra.


Intensity to force translation: a new effect of stimulus-response compatibility revealed by analysis of response time and electromyographic activity of a prime mover.
In reaction time studies of stimulus-response compatibility, emphasis has been placed on the influence of spatial stimulus-response relationships, but what seems to be essential for the emergence of an effect of stimulus-response compatibility is the existence of a conceptual match between stimulus and response variables. This notion was at the origin of the present study to assess the compatibility relationship between the intensity of a visual stimulus and the force of a voluntary muscle contraction. A stimulus-response compatibility effect was demonstrated. This effect was entirely due to premotoric processes.


Associated social factors of prevalent asthma in adults and the very old in the UK.
Social determinants of asthma in adults and the very old have received little attention. Hence, it was aimed to examine social determinants of asthma in adults and the very old in a national population-based setting. Data were analyzed in the UK Longitudinal Household Survey, 2009-2010. Information on demographics, living and work conditions, self-reported ever asthma and age of onset was obtained by household interview. Regional difference was also examined. Analysis involved t-test and logistic regression modeling. Of 50 994 people included in the cohort, 6269 (12.3%) had ever asthma. In 2977 people, it occurred in the adulthood (16+ years) and only 91 people had their first asthma (incident asthma) at the age when they were interviewed. Education was borderline associated with asthma in the very old. In the young and middle-aged adults, however, birth place had a significant impact. Additionally, there was no regional difference in asthma prevalence across the entire UK.


Mental turmoil, suicide risk, illness perception, and temperament, and their impact on quality of life in chronic daily headache.
To evaluate the relationship among quality of life, temperament, illness perception, and mental turmoil in patients affected by chronic daily headache with concomitant medication overuse headache. Participants were 116 consecutive adult outpatients admitted to the Department of General Medicine of the Sant'Andrea Hospital in Rome, between January 2007 and December 2007 with a diagnosis of chronic daily headache (illness duration >5 years). Patients were administered the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-autoquestionnaire version (TEMPS-A), the Beck Hopelessness Scale (BHS), the Hamilton Rating Scale for Depression (HAM-D), the Mini-International Neuropsychiatric Interview (MINI), the Revised Illness Perception Questionnaire (IPQ), the Suicide Score Scale (SSS), and the Quality of Life Index (QL-Index). Twenty-eight percent of the patients evidenced moderate to severe depression, and 35% evidenced severe hopelessness. Analyses also indicated that quality of life, temperament, illness perception, and psychological turmoil are associated. However, a hierarchical multivariate regression analysis with quality of life as dependent variable indicated that only a model with mental turmoil variables may fit data; further, only the MINI suicidal intent resulted associated with quality of life (standardized regression coefficient = -0.55; t = -3.06; P < 0.01). Suicide risk may play a central role in affecting the quality of life of patients with chronic headache. The investigation of the interplay of factors that precipitate suicide risk should include assessment of chronic headache and its effects on wellbeing.


Modifications of preputial unfurling to reduce postoperative edema in buried penis.
Buried penis is a result of penile skin deficiency and inadequate attachment of the skin to the Buck's fascia. Prolonged postoperative edema (>1 month) has been seen in some patients after preputial unfurling. Some modifications which may reduce this complication are described. Thirty-two boys with buried penis, aged 14 months to 12 years, underwent the surgical procedure. A circumferential incision was made at the junction of the outer and inner prepuce. The subcutaneous tissue was removed from the inner prepuce and degloved from the Buck's fascia, so that a thin inner prepuce could be sutured directly to Buck's fascia. Excessive prepuce was trimmed. Reapproximation of the outer and the inner prepuce completed the procedure. A narrow skin ring at the penile base, which may compromise venous and lymphatic flow, was avoided by dorsal or ventral incision. Mild edema was seen in some patients but subsided within a month. Satisfactory cosmetic results were achieved. This procedure unfurls the inner prepuce to cover the penile shaft. Ideal cosmetic results can be achieved if some details of the procedure are emphasized.


Metal-ion-directed site-specificity of hydroxyl radical detection.
A wide variety of .OH detectors are in use for determination of biological .OH production. The chemical generation of .OH is site-specific with respect to the metal-binding site, and thus .OH detectors with metal-binding properties may affect the biological damage and bias .OH detection. The present study shows that both salicylate and phenylalanine, added as low molecular weight .OH indicators, decreased Cu(II) binding to erythrocyte ghosts. In a cell-free system, Cu(II) complexed to both salicylate and phenylalanine. Phenylalanine is a stronger Cu(II) chelator than salicylate, both when competing for Cu(II) bound to ghosts and when competing directly with each other. When OH radicals were generated by ascorbate and Cu(II), the amount of .OH detected as dihydroxybenzoates was proportional to the amount of .OH produced. However, when phenylalanine was added to this system, the efficiency of .OH detection by salicylate strongly decreased, concomitant with the transfer of Cu(II) binding from salicylate to the amino acid. This decrease was larger than that predicted by calculations for random competition of the two detectors for .OH. Deoxyribose and mannitol, which do not bind copper appreciably, competed poorly with salicylate for the .OH. Hydroxylation of phenylalanine, on the other hand, was only slightly affected by the presence of salicylate and unaffected by deoxyribose and mannitol. These results suggest that the detection of .OH by low molecular weight .OH indicators was related to the relative affinity of the detectors for the catalyzing metal, and thus partially site-specific. Furthermore, glutamate, which does not contain an aromatic ring but binds Cu(II) with considerable affinity, competed strongly with salicylate for the .OH, indicating that metal-binding properties rather than the presence of an aromatic ring were the cause of the deviation from random competition. The results indicate that .OH indicators with metal-binding properties affect the distribution of catalytic metal ions in a biological system, causing a shift of free radical damage and localizing a site-specific reaction of .OH on these detectors, with a resulting positive bias in the apparent .OH production.


Analysis of an enzyme-substrate complex by X-ray crystallography and transferred nuclear Overhauser enhancement measurements: porcine pancreatic elastase and a hexapeptide.
The hexapeptide substrate Thr-Pro-nVal-NMeLeu-Tyr-Thr reacts with porcine pancreatic elastase sufficiently slowly that accelerated crystallographic data collection procedures and two-dimensional transferred nuclear Overhauser enhancement measurements could be used to study the geometry of binding. Both studies report a time-averaged population of the Michaelis complex state, prior to proteolysis. This result provides an important data point along the reaction coordinate pathway for serine proteases. Crystallographic data to 1.80-A resolution were used in the structure analysis with refinement to an R-factor of 0.19.


Invasion of a soft contact lens by Exophiala jeanselmei.
The invasion of a soft contact lens by Exophiala jeanselmei is documented. All species in this genus are pathogenic. In humans E. jeanselmei is a recognized cause of mycetoma, phaeohyphomycosis and keratomycosis. This fungus has not been previously listed among lens invaders.


Bone mineral content measurement in small infants by single-photon absorptiometry: current methodologic issues.
Single-photon absorptiometry (SPA), developed in 1963 and adapted for infants by Steichen et al. in 1976, is an important tool to quantitate bone mineralization in infants. Studies of infants in which SPA was used include studies of fetal bone mineralization and postnatal bone mineralization in very low birth weight infants. The SPA technique has also been used as a research tool to investigate longitudinal bone mineralization and to study the effect of nutrition and disease processes such as rickets or osteopenia of prematurity. At present, it has little direct clinical application for diagnosing bone disease in single patients. The bones most often used to measure bone mineral content (BMC) are the radius, the ulna, and, less often, the humerus. The radius appears to be preferred as a suitable bone to measure BMC in infants. It is easily accessible; anatomic reference points are easily palpated and have a constant relationship to the radial mid-shaft site; soft tissue does not affect either palpation of anatomic reference points or BMC quantitation in vivo. The peripheral location of the radius minimizes body radiation exposure. Trabecular and cortical bone can be measured separately. Extensive background studies exist on radial BMC in small infants. Most important, the radius has a relatively long zone of constant BMC. Finally, SPA for BMC in the radius has a high degree of precision and accuracy.


Retention and transport of an anaerobic trichloroethene dechlorinating microbial culture in anaerobic porous media.
The influence of solution chemistry on microbial transport was examined using the strictly anaerobic trichloroethene (TCE) bioaugmentation culture KB-1(®). A column was employed to determine transport behaviors and deposition kinetics of three distinct functional species in KB-1(®), Dehalococcoides, Geobacter, and Methanomethylovorans, over a range of ionic strengths under a well-controlled anaerobic condition. A quantitative polymerase chain reaction (qPCR) was utilized to enumerate cell concentration and complementary techniques were implemented to evaluate cell surface electrokinetic potentials. Solution chemistry was found to positively affect the deposition rates, which was consistent with calculated Derjaguin-Landau-Verwey-Overbeek (DLVO) interaction energies. Retained microbial profiles showed spatially constant colloid deposition rate coefficients, in agreement with classical colloid filtration theory (CFT). It was interesting to note that the three KB-1(®) species displayed similar transport and retention behaviors under the defined experimental conditions despite their different cell electrokinetic properties. A deeper analysis of cell characteristics showed that factors, such as cell size and shape, concentration, and motility were involved in determining adhesion behavior.


Osteomorphological features of the appendicular skeleton of gazelles, genus Gazella Blainville 1816, bohor reedbuck, Redunca redunca (Pallas, 1767) and bushbuck, Tragelaphus scriptus (Pallas, 1766).
Examined the osteomorphological features of the appendicular skeleton of Grant's gazelle (Gazella granti), bohor reedbuck (Redunca redunca) and bushbuck (Tragelaphus scriptus). Osseous remains of these medium sized antelopes are often encountered in African late Quaternary archaeological sites, but their specific identification poses considerable problems to the archaeozoologist. A key has been developed to meet this recurrent problem and a number of diagnostic osteomorphological features, allowing a distinction between the bovids mentioned, are established. The osteomorphological characteristics, typical for Grant's gazelle have also been observed in the eight other extant African gazelles and in two Asian species, the goitred gazelle (Gazella subgutterosa) and the mountain gazelle (Gazella gazella).


High incidence area of cattle cancer with a possible interaction between an environmental carcinogen and a papilloma virus.
Cattle in upland areas of Scotland and northern England are substantially more prone to alimentary cancer than those of the immediately neighbouring lowlands, and epidemiological evidence implicates a combination of papilloma virus and bracken in the aetiology of the disease. Here Professor Jarrett outlines the circumstantial case against these agents and discusses its implications.


Seabirds as anthropization indicators in two different tropical biotopes: A One Health approach to the issue of antimicrobial resistance genes pollution in oceanic islands.
Antimicrobial resistance is a quintessential One Health issue, among the most serious 21st century global threats to human health. Seabirds may act as sentinels of natural and anthropogenic changes in the marine ecosystem health, including pollution by antimicrobial resistance genes (ARGs). We used real time PCR to identify and quantify 22 plasmid-mediated ARGs in the gastrointestinal microbiome of six wild seabird species, comparing an anthropized (Fernando de Noronha Archipelago - FNA) and a pristine biotope (Rocas Atoll - ROA), Brazil. Of 257 birds, 218 (84.8%) were positive to at least one ARG. ARG classes encoding resistance to tetracyclines (75.1%), quinolones (10.5%) and phenicols (10.5%) were the most prevalent, with tetracyclines significantly greater than the remaining classes (p < 0.05). Genes tet(S) (29.2%), tet(A) (28.8%), and tet(B) (24.9%) were the most commonly found and had a significantly greater prevalence when compared to the remaining ARGs (p < 0.05). The anthropized biotope presented statistically significant higher prevalence of sulfonamide- and quinolone-encoding ARGs in comparison with the pristine (respectively, p = 0.01 and p = 0.03), and higher sulII gene prevalence (p = 0.04), consistent with anthropogenic pressure. Migratory species (only present in ROA) showed statistically significant higher mcr-1 (polymyxins) and blaTEM (betalactam) prevalences (respectively, p = 0.009 and p = 0.02), and mcr-1 percentage load (p = 0.0079) in comparison with non-migratory. To our knowledge, this is the largest ARGs survey based on direct detection and quantification in seabirds worldwide, and the first to evaluate non-synanthropic species in oceanic islands. This is the first detection of mcr-1 in wild free-ranging seabirds in Brazil and in free-ranging migratory non-synanthropic seabirds worldwide. Our findings show the importance of biological and ecological factors, highlighting the role of seabirds as anthropization sentinels and ARGs-pollution environmental indicators (even in a pristine biotope), and their involvement in the One Health epidemiological chain of ARGs.


Pyrithione Zn selectively inhibits hypoxia-inducible factor prolyl hydroxylase PHD3.
Increasing evidence emphasizes the role of the hypoxia-inducible factor (HIF) prolyl hydroxylase (PHD) isoforms in regulating non-HIF substrates, but isoform selective PHD inhibitors under physiological conditions have not yet been reported. Here we have identified pyrithione Zn (PZ) as a potent, isoform-selective PHD3 inhibitor. The IC50 value of PZ was determined as 0.98 μM for PHD3, while it did not show any inhibitory activity toward full length and truncated PHD2 up to 1 mM. The selective efficacy of PZ was further demonstrated at the cellular level by observing inhibition of the PHD3-dependent DNA damage response pathway without stabilization of HIF-1α.


Apocalypse Now!: From Freud, Through Lacan, to Stiegler's Psychoanalytic 'Survival Project.
The objective of this article is to explore the value of psychoanalysis in the early twenty-first century through reference to Freud, Lacan, and Stiegler's work on computational madness. In the first section of the article I consider the original objectives of psychoanalysis through reference to what I call Freud's 'normalisation project', before exploring the critique of this discourse concerned with the defence of oedipal law through a discussion of the post-modern 'individualisation project' set out by Deleuze and Guattari and others. Tracking the development of 'the individualisation project' in history, I consider its connections with the cybernetic theories of Wiener and Shannon in the psycho-cyber-utopianism of the 1990s, before moving on to consider the other side of the psychoanalytic-cybernetic interaction through a discussion of Jacques Lacan's rereading of Freud's Beyond the Pleasure Principle in the second section of the article. In reading Lacan's seminar on Freudian drive in terms of the cybernetic repression of death, I set up the conclusion to the article which involves a discussion of Bernard Stiegler's 'survival project' that relies on a recognition of the limit of death in order to produce human significance and oppose the madness of our contemporary computational reality.


Chromatographic resolution of angiotensin II receptor antagonists (sartans).
First time a simple, sensitive and unified quantification method has been developed to analyze the complete class of angiotensin II receptor antagonists which are used in the treatment of hypertension either alone or in combination with some other drugs. The most important advantage of developed method was that the eight separate drugs can be determined on a single chromatographic system without modifications in detection wavelength and mobile phase. The drugs were separated on a Purospher Star 4.6mm×25cm, 5μm, C18 column maintained at 40°C with 1mLmin(-1) flow rate using ultra violet detection at 254nm. Good separation (Rs>2.0) was achieved in a short analysis allowing simultaneous determination of all eight sartans. The effect of variation in flow rate, detection wavelength and column oven temperature was also studied. The proposed method was statistically validated in terms of precision, accuracy, linearity, specificity and robustness. The newly developed method proved to be specific, robust and accurate for the quantification of eight sartans in commercial pharmaceutical formulations.


A Note on Derivatives of Isoniazid, Rifampicin, and Pyrazinamide Showing Activity Against Resistant Mycobacterium tuberculosis.
Drug-resistant tuberculosis (DR-TB) is a serious problem that impedes the success of the TB control program. Of note, multidrug-resistant (MDR)-TB and extensively drug-resistant (XDR)-TB have certainly complicated the scenario. One of the possible strategies to overcome drug resistance in an economic and simple manner would involve modification of existing anti-TB drugs to obtain derivatives that can work on resistant TB bacilli. These may have improved half-life and increased bioavailability, be more efficacious, and serve as cost-effective alternatives, as compared to new drugs identified through conventional methods of drug discovery and development. Although extensive literature is available on the activity of various derivatives of first-line drugs (isoniazid, rifampicin and pyrazinamide) on drug-susceptible Mycobacterium tuberculosis (MTB), reports on the activity of derivatives on resistant MTB are very limited, to our knowledge. In light of this, the present review aims to provide a concise report on the derivatives of first-line drugs that have the potential to overcome the resistance to the parental drug and could thus serve as effective alternatives.


Augmented exercise plasma noradrenaline with impaired chronotropic responsiveness in patients with hypertrophic cardiomyopathy.
1. There is controversy regarding plasma catecholamine levels in patients with hypertrophic cardiomyopathy (HCM) and few data exist on serial plasma catecholamine measurements during exercise. The present study determined whether cardiovascular and plasma catecholamine responses to exercise were altered in patients with HCM. 2. Plasma noradrenaline (NA) and adrenaline were measured at rest, at the end of each stage during exercise and immediately and 5 min after submaximal treadmill exercise in 15 patients with non-obstructive HCM (13 males, two females; mean (+/- SEM) age 54 +/- 3 years) and in 15 age- and sex-matched controls. The ratio of the increment in heart rate (HR) divided by the increment in plasma NA during exercise (delta HR/delta NA) was used as an index of chronotropic sympathetic responsiveness to exercise. 3. Exercise duration was shorter (11.2 +/- 0.6 vs 8.7 +/- 0.6 min for control vs HCM, respectively; P < 0.01) and diastolic blood pressure was significantly higher at stages I and II of modified Bruce protocol HCM. 4. Resting plasma NA levels (149 +/- 17 vs 167 +/- 28 pg/mL for control vs HCM, respectively; NS) were not different, but plasma NA levels at stages I and II were significantly higher in HCM than in controls (243 +/- 26 vs 399 +/- 69 pg/mL (P < 0.05) and 308 +/- 30 vs 548 +/- 110 pg/mL (P < 0.05), respectively). 5. Peak plasma NA levels were not significantly higher in HCM than in controls (578 +/- 59 vs 918 +/- 184 pg/mL, respectively; NS). 6. The ratio delta HR/delta NA was significantly lower in HCM compared with control at stages I and II (0.49 +/- 0.10 vs 0.21 +/- 0.05 (P < 0.05) and 0.38 +/- 0.06 vs 0.20 +/- 0.05 (P < 0.05), respectively). There were no differences in plasma adrenaline responses during exercise between the two groups. 7. Patients with HCM had augmented plasma NA levels during submaximal exercise with a higher diastolic blood pressure response. Chronotropic sympathetic responsiveness was impaired during the early stages of exercise in patients with HCM.


Purification of and production of an antibody against a 63,000 Mr stimulus-sensitive phosphoprotein in Paramecium.
In vivo labeling of Paramecium cells with 32Pi most heavily labels a minor 63-kDa protein that undergoes a rapid, Ca2+-dependent dephosphorylation when the cell is stimulated to release. This stimulus-sensitive phosphoprotein was isolated and purified to apparent homogeneity. A polyclonal affinity purified antibody made against the purified protein recognizes both the phosphorylated and dephosphorylated forms of the protein. The phosphorylated 63-kDa protein is found in the cytosolic fraction; it is slightly acidic with two isoelectric forms at pI 5.8 and 6.2 and probably exists as a monomeric 60-65-kDa polypeptide in the native state. The labeled phosphoamino acid of the protein is phosphoserine. The affinity purified antibody recognizes a third isoelectric form at pI 6.3 that appears unlabeled. The specificity of the antibody was confirmed by showing that it immunoprecipitates the correct protein, i.e. the stimulus-sensitive 63-kDa phosphoprotein. The availability of purified 63-kDa protein as well as an antibody against it will now allow molecular, biochemical, and immunocytochemical studies into the role of this protein in the mechanism of exocytosis.


Diffuse lymphomatous polyposis of the gastrointestinal tract. A case report with immunohistochemical studies.
A case of diffuse lymphomatous polyposis of the gastrointestinal tract is reported. The patient presented with abdominal pain and weight loss and x-rays revealed multiple polyps involving the entire gastrointestinal tract. Biopsies confirmed the diagnosis of lymphomatous polyposis. The patient also had involvement of the bone marrow and supraclavicular lymph node. Immunologically this lymphoma was characterized as a monoclonal proliferation of B lymphocytes bearing immunoglobulin M, type kappa. Diffuse lymphomatous polyposis of the gastrointestinal tract appears to be a generalized malignancy of uncommitted B cells of Peyer's patches. The migratory properties of these cells may account for the tendency to dissemination of lymphomatous polyposis. Diffuse lymphomatous polyposis of the gastrointestinal tract is a distinct entity, separate from the diffuse gastrointestinal lymphoma known as Mediterranean-type lymphoma.


Comparative Analysis of Continuous Suturing, Interrupted Suturing, and Cyanoacrylate-Based Lid Techniques for End-to-End Microvascular Anastomosis: Laboratory Investigation.
Mastery of the microsurgical anastomosis is an indispensable component of neurosurgical training. However, in many resource-limited countries, the training, materials, and equipment to obtain these surgical and decision making skills are severely lacking. This study aimed to compare different suturing techniques for microvascular anastomosis and to complete a comparative assessment of the performance of a young neurosurgeon when using the various techniques. We compared 3 end-to-end suturing techniques for microvascular anastomosis: interrupted suturing, continuous suturing, and a 2-octyl-cyanoacrylate-based lid technique using an umbilical artery model. We assessed the subjective difficulty of the suturing technique, the time needed to perform the procedure, and the flow rate and leakage of the vessel after each technique. This study was designed to use materials that would be available in developing countries. Surgical apparatus used, such as operating microscopes, were first-generation technology, and testing procedures were designed for neurosurgical residents in developing countries. The mean times to complete the anastomosis were 20.7 ± 7.7 minutes for the interrupted technique, 26.4 ± 7.7 minutes for the continuous technique, and 12.5 ± 2.5 minutes for the lid technique; these values were significantly different (P < 0.01). The differences among the 3 techniques in leakage and flow rates and subjective difficulty in performance were not significant. Suturing time was the only statistically significant difference among the 3 anastomotic techniques, with the lid technique apparently the quickest to perform. Such techniques can be designed to assess microsurgical abilities and help neurosurgery residents in developing countries improve their surgical skills and techniques.


A brief overview of nuclear medicine in China.
The year 1956 witnessed the birth of Nuclear Medicine in China, when the first course, Biomedical Applications of Isotopes, was offered in our country by the Peking Union Medical College (PUMC). This course was preceded by a training course in nuclear instruments in which students learned to construct the radiation detection devices required for performing experiments using radioisotopes. In 1958, several courses in clinical nuclear medicine brought up the first generation of nuclear medicine physicians in China. Historically, some of the chief events include: (1) operation of the first reactor, producing 33 radioactive isotopes in 1958; (2) first linear scanner built in 1960; (3) setting up an organization for the control of radiopharmaceuticals in 1961; (4) distribution of the first batch of cyclotron-produced isotopes in 1963; (5) development and use of the first radioimmunoassay (RIA) procedure in 1963; (6) production of tritium in 1964; (7) production of 99.8% enriched heavy water in 1965; (8) supply of 99mTc and 113mIn generators in 1972; (9) first gamma camera imported in 1972 and first homemade gamma camera installed in 1977; (10) founding of Chinese Society of Nuclear Medicine (CSNM) in 1980; (11) publication of the Chinese Journal of Nuclear Medicine beginning in 1981; (12) first single photon emission computed tomography (SPECT) imported in 1983. At present, there are 556 nuclear medicine departments in China with 4,000 staff.(ABSTRACT TRUNCATED AT 250 WORDS)


Sudden Onset Tic and Tic-Like Presentations in Older Adolescents and Adults.
The past 3 years have seen an unprecedented increase in patients with functional tic-like behaviors (FTLB), a previously rare form of functional movement disorder (FMD) that can be mistaken for Tourette syndrome (TS). This article contrasts the patient characteristics, phenomenology, risk factors, and comorbidities of FTLB and TS to define criteria for differential diagnosis. Clinical issues, treatments, theoretical explanations, and future research questions are discussed. FTLB predominately affect females, with a later onset of movements and vocalizations that are more complex, directional, severe, debilitating, and non-suppressible compared to TS. Psychosocial stressors from the pandemic, exposure to tic-content on social media, and comorbid anxiety and depression are etiological factors. Cognitive behavioral therapies appear to be effective treatment strategies. Creation of standardized clinical practice guidelines for diagnosis and treatment of this now common FMD are recommended. Etiological explanations fit coherently within a biopsychosocial model of pathology.


[Pericardial perforation 2.5 years after kyphoplasty. A rare complication after cement extravasation].
Kyphoplasty is an established method in the treatment of osteoporotic spine fractures. In 10-15% of cases cement extravasation and leakage into veins occur. We report about the rare course of an extravasation. In 2008 an osteoporotic compression fracture of L(4) and L(5) in a 62-year-old female patient was treated by kyphoplasty. In the treated vertebra filling of an outgoing vein towards the proximal right side occurred. Postoperatively the patient was free of complaints (VAS preoperative 9/10, postoperative 1/10). In the chest X-ray a small asymptomatic filling of a lung vessel on the left side was present. The patient arrived as an emergency case 2.5 years later with decompensated heart failure. In the chest CT and angiography cement emboli in the lung were seen as well as a perforation of the pericardium with beginning tamponade. A thoracotomy was performed. Intraoperatively two 4 cm long sharp cement pieces were removed from the heart, which had perforated the right ventricle. Leakages were closed by suture. The patient survived the operation and was dismissed after 2 weeks of intensive care for rehabilitation and from there dismissed home. Six months later she had no more problems. When filling vertebra in several levels one must pay attention to introducing cement with a thick consistency, otherwise venous emboli and lung emboli may occur. These are as a rule asymptomatic, but may result in exceptional life-threatening complications.


Impact of Persisting Amblyopia on Socioeconomic, Health, and Well-Being Outcomes in Adult Life: Findings From the UK Biobank.
This study aimed to investigate associations between persisting amblyopia into adulthood and its "real-life" impacts and inform the current debate about the value of childhood vision screening programs. Associations between persisting amblyopia and diverse socioeconomic, health, and well-being outcomes were investigated in multivariable-adjusted (sex, age, ethnicity, deprivation) regression models, with 126 400 participants (aged 40-70 years) of the UK Biobank with complete ophthalmic data. Analysis by age group (cohort 1, 60-70 years; cohort 2, 50-59 years; cohort 3, 40-49 years) assessed temporal trends. Of 3395 (3%) participants with confirmed amblyopia, overall 77% (2627) had persisting amblyopia, declining from 78% in cohort 1 to 73% in cohort 3. The odds of persisting amblyopia were 5.91 (5.24-6.66) and 2.49 (2.21-2.81) times greater in cohort 1 and cohort 2, respectively, than cohort 3. The odds were also higher for more socioeconomically deprived groups and for white ethnicity. Reduced participation in sport, adverse general and mental health, and well-being were all independently associated with persisting amblyopia, with the strongest associations in the youngest cohorts. Associations with lower educational attainment and economic outcomes were only evident in the oldest cohort. There has been a decline in the overall frequency of persisting amblyopia since the introduction of universal child vision screening in the United Kingdom. Nevertheless, most adults treated for amblyopia in childhood have persisting vision deficits. There was no evidence that persisting amblyopia has vision-mediated effects on educational, employment-related, or economic outcomes. The observed adverse outcomes were largely those not directly mediated by vision. Patients undergoing treatment should be counseled about long-term outcomes.


Altering tissue tropism of Listeria monocytogenes by ectopically expressing human E-cadherin in transgenic mice.
The Gram-positive bacterium Listeria monocytogenes invades a variety of cells in vitro and in vivo. Here, we show that L. monocytogenes is able to enter muscle cells if provided with the appropriate host receptor. Using a cardiac-specific promoter, human E-cadherin was misexpressed in the heart of transgenic mice. First, we demonstrate that L. monocytogenes is capable of infecting the E-cadherin-expressing, but not the N-cadherin-expressing cardiomyocytes in vitro. Second, we show that L. monocytogenes infects the heart of transgenic animals after administering the bacteria intravenously. This unique system may prove useful for understanding basic aspects of L. monocytogenes cell biology by comparing infection of muscle versus epithelial cells.


Access to anticancer drugs: many evidence-based treatments are off-label and unfunded by the Pharmaceutical Benefits Scheme.
The off-label use of a drug refers to a use outside the terms of its approval by the Therapeutic Goods Administration (TGA). It is also possible to prescribe unlicensed drugs under the TGA's special access scheme. A high rate of off-label prescribing has previously been reported in cancer. Our study aimed to document the disparity between evidence-based clinical guidelines for anticancer therapy, product approval and funding status of these agents within an academic tertiary/quaternary cancer centre. All chemotherapy protocols approved for use in our specialist oncology centre were assessed to determine if the drugs were off-label or unlicensed for that indication based on review of their current product information. The Pharmaceutical Benefits Scheme (PBS) funding status for each protocol was subsequently assessed. A total of 448 protocols containing 82 different drugs across 15 tumour groups was identified. Overall, 189 (42.2%) of protocols were off-label, and three (0.7%) were unlicensed. This resulted in all 192 protocols being unfunded by the PBS. Of the 189 off-label protocols, 132 (69.9%) were based on established evidence-based treatment guidelines, and a further 39 (20.6%) was based on phase II or III clinical trial data. Over 90% of off-label protocols are supported by established treatment guidelines or published peer-reviewed research even though the medications are not approved for that particular use by the TGA. However, these off-label protocols are unfunded by the PBS; this results in a marked inequality of access to appropriate medications for cancer patients across Australia.


Effectiveness of rotavirus vaccine in preventing hospitalization due to rotavirus gastroenteritis in young children in Connecticut, USA.
Rotavirus vaccine was recommended for use in US infants to prevent rotavirus gastroenteritis (RGE) in February 2006. This matched case control study assessed the effectiveness of rotavirus vaccine in preventing hospitalization of young. Cases were vaccine-eligible children 8 weeks-3 years of age, hospitalized due to laboratory-confirmed RGE. Cases (n=42) were matched to 2 control groups: (a) hospitalized controls (n=80): children hospitalized for reasons other than RGE, matched to the cases by age and time of presentation and (b) community controls (n=73): non-hospitalized children matched by age and medical practice. Adjusted vaccine effectiveness against hospitalization with RGE in vaccine eligible children receiving at least one dose of vaccine was 94.3% (95% C.I.: 55.4%-99.3%; p=0.006) for hospitalized controls and 96.9% (95% C.I.: 59.4%-99.8%; p=0.008) for community controls.


Outcomes of Reconstruction of the Flexible Adult-acquired Flatfoot Deformity.
Reconstruction of the flexible adult-acquired flatfoot deformity (AAFD) is controversial, and numerous procedures are frequently used in combination, including flexor digitorum longus transfer, medializing calcaneal osteotomy (MCO), heel cord lengthening/gastrocnemius recession, lateral column lengthening (LCL), Cotton osteotomy or first tarsometatarsal fusion, and spring ligament reconstruction. This article summarizes recent studies demonstrating that patients have significant improvements after operative treatment of flexible AAFD. It reviews current literature on clinical and radiographic outcomes of the MCO, LCL, and Cotton osteotomies. The authors describe how this information can be used in surgical decision making in order to tailor operative treatment to an individual patient's deformity.


Influence of plasma protease activation on electroimmunoassay and nephelometry of plasma fibronectin in sepsis.
In vitro experiments have shown that proteases such as trypsin, kallikrein and plasmin may split plasma fibronectin, yielding changes in apparent mass concentration, i.e.: a decrease when using immunonephelometry (IN), and an increase when using electroimmunoassay (EIA). In the present in vivo study, plasma from 49 patients with severe infections was assayed for fibronectin by IN and EIA, and for prekallikrein, plasminogen and antithrombin. In patients with normal prekallikrein (n = 26) and plasminogen (n = 23), the agreement between the two fibronectin assay methods was good (ratio EIA/IN = 0.99 +/- 0.06); a similar good agreement was found in 45 healthy blood donors (ratio 0.97 +/- 0.02). In contrast, the 20 patients with low prekallikrein showed fibronectin values that were significantly higher by EIA than by nephelometry (ratio 1.27 +/- 0.10, p less than 0.01). Similarly, the 26 patients with low plasminogen had a significantly increased ratio (1.21 +/- 0.09, p less than 0.05). No such difference was seen, however, between patients with low or normal antithrombin. Thus, kallikrein and plasmin activation in vivo appear to increase the fibronectin concentration measured by EIA, possibly due to the formation of small fragments with increased electrophoretic motility.


About the presence of a thermolabile (TL) antigenic fraction in Leptospira interrogans.
Antisera prepared with living serovars of Leptospira interrogans have a fraction anti-TL able to neutralize TL antigen of Leptospira strains. After neutralization, any leptospiral serovar is able to adsorb heterologous antisera prepared with living strains.


[Cardiopulmonary resuscitation. The effect of severe hypothermia on clinical outcome].
Evaluation of outcome after CPR in severe hypothermic patients. Perspective study from October 1995 to April 1996. First aid team of Italian Red Cross, Busto Arsizio (Varese), Italy. A population of 22 patients in cardiac arrest in which CPR was performed immediately after rescue team's arrival is studied. ECG, core temperature, SpO2 and MAP were monitored whereas vital parameters were present during Basic Life Support. Outcome after CPR was evaluated with GOS scale. It has been observed that severe hypothermia and time of cardiac arrest impact on the clinical outcome after CPR. The high mortality rate after CPR with BLS standard is worsened by a core temperature < or = 33 degrees C. Severe hypothermia seems to have a dangerous effect upon outcome after cardiopulmonary resuscitation; heating systems for body temperature could prevent this situation improving CPR results.


Tolerability of Gemcitabine Plus Cisplatin for Treatment of Urothelial Cancer in the Elderly Population.
Gemcitabine plus cisplatin is the standard of care for metastatic urothelial cancer and is frequently used in the neoadjuvant and adjuvant setting as well. However, the optimal dose and schedule for patients aged ≥ 65 years is not clear. We performed a retrospective study to determine the tolerability of gemcitabine plus cisplatin for treatment of urothelial cancer in the elderly population. A total of 28 patients aged ≥ 65 years with urothelial cancer treated with gemcitabine plus cisplatin on a 21-day schedule from January 1, 2008 to August 31, 2013 were included in the present study. Of the 28 patients, 16 (57.1%) received gemcitabine plus cisplatin in the neoadjuvant setting. The most common dosing regimen was gemcitabine 1250 mg/m(2) given on days 1 and 8 plus cisplatin 70 mg/m(2) on day 1 every 21 days, with some receiving gemcitabine at a dose of 1000 mg/m(2). The primary reason behind the dose modifications and treatment delays with the higher gemcitabine dose was hematologic toxicity. Two patients discontinued treatment because of renal dysfunction, with one developing a grade 4 elevation in serum creatinine. One patient developed febrile neutropenia; however, this patient did not receive growth factor support for primary prophylaxis of febrile neutropenia. Gemcitabine plus cisplatin overall is a reasonably well-tolerated treatment regimen for patients aged ≥ 65 years. The results of the present study support the use of a lower gemcitabine dose of 1000 mg/m(2), because it was better tolerated.


Variations in the organization of repetitive DNA sequences in the genomes of Plasmodium falciparum clones.
Repetitive DNA in cultured Plasmodium falciparum was examined by restriction digestion and transfer hybridization, using cloned repetitive DNA probes. The arrangement of repetitive DNA was unstable: after 6 months culture of a cloned population, variations could be detected. Significant differences can be seen between clones derived from a single isolate, and are even more marked between isolates of diverse geographical origin. No cross-species conservation was seen for the sequences examined, and no relationship was observed between their representation in the P. falciparum genome and the potential for sexual differentiation.


A three-dimensional cryo-electron microscopy structure of the bacteriophage phiKZ head.
The three-dimensional structure of the Pseudomonas aeruginosa bacteriophage phiKZ head has been determined by cryo-electron microscopy and image reconstruction to 18A resolution. The head has icosahedral symmetry measuring 1455 A in diameter along 5-fold axes and a unique portal vertex to which is attached an approximately 1800 A-long contractile tail. The 65 kDa major capsid protein, gp120, is organized into a surface lattice of hexamers, with T = 27 triangulation. The shape and size of the hexamers is similar to the hexameric building blocks of the bacteriophages T4, phi29, P22, and HK97. Pentameric vertices of the capsid are occupied by complexes composed of several special vertex proteins. The double-stranded genomic DNA is packaged into a highly condensed series of layers, separated by 24 A, that follow the contour of the inner wall of the capsid.


Anterior Cruciate Ligament Reconstruction Increases the Risk of Hamstring Strain Injury Across Football Codes in Australia.
The aim of this study was to determine the impacts of anterior cruciate ligament reconstruction (ACLR) and recent (< 12 months) hamstring strain injury (HSI) on (1) future HSI risk, and (2) eccentric knee flexor strength and between-limb imbalance during the Nordic hamstring exercise. A secondary goal was to examine whether eccentric knee flexor strength was a risk factor for future HSI in athletes with prior ACLR and/or HSI. In this prospective cohort study, 531 male athletes had preseason eccentric knee flexor strength tests. Injury history was also collected. The main outcome was HSI occurrence in the subsequent competitive season. Overall, 74 athletes suffered at least one prospective HSI. Compared with control athletes, those with a lifetime history of ACLR and no recent HSI had 2.2 (95% confidence interval [CI] 1.1-4.4; p = 0.029) times greater odds of subsequent HSI while those with at least one HSI in the previous 12 months and no history of ACLR had 3.1 (95% CI 1.8-5.4; p < 0.001) times greater odds for subsequent HSI. Only athletes with a combined history of ACLR and recent HSI had weaker injured limbs (p = 0.001) and larger between-limb imbalances (p < 0.001) than uninjured players. An exploratory decision tree analysis suggested eccentric strength may protect against HSI after ACLR. ACLR and recent HSI were similarly predictive of future HSI. Lower levels of eccentric knee flexor strength and larger between-limb imbalances were found in athletes with combined histories of ACLR and recent HSI. These findings may have implications for injury rehabilitation.


Can the transoral approach secure a cancer-free deep margin in tonsil cancer?
To verify whether the submuscular plane of the constrictor muscle, which is the resection margin in a transoral approach, is sufficient for securing a cancer-free deep margin in tonsil cancer patients. Retrospective analysis of medical records and pathology specimens was done in sixty-two patients who were diagnosed with tonsil cancer and underwent surgery via a combined transoral-transcervical (transoral and transcervical lateral pharyngotomy) approach. The status of constrictor muscular invasion in tonsil cancer patients according to the TN stage and its predictors was investigated. Invasion or penetration of the constrictor muscle was found in three (27.3%), 30 (76.9%), and 12 (100%) stage T1, T2, and T3-4 patients, respectively. In the univariate analysis, invasion or penetration of the constrictor muscle was significantly correlated with gender (p=0.004), stage >T2 (tumor ≥2 cm; p=0.001), and N(+) (p=0.004). The multivariate analysis showed that stage >T2 [tumor ≥2 cm; odds ratio (OR), 18.226; 95% confidence interval (CI), 2.976-111.608; p=0.002] and N(+) (OR, 7.560; 95% CI, 1.478-38.671; p=0.015) were significantly correlated with an increased risk of muscle invasion or penetration. The transoral approach is seems to be insufficient for securing a cancer-free deep margin in tonsil cancer beyond stage T2 or N1. The tumor beyond this stage should be treated more aggressively using multiple treatment modalities including radical surgery, chemotherapy, and radiotherapy.