Evaluation of novel agars for the enumeration of Campylobacter spp. in poultry retail samples.
The purpose of this study was to examine the performance of novel agars for the identification and enumeration of Campylobacter species. The analytical sensitivity and specificity of Campylobacter Selective agar (CASA), Brilliance CampyCount agar (BCCA) and CampyFoodIDagar (CFA) for 84 Campylobacter spp. isolates and 50 non-Campylobacter spp. isolates from 37 distinct genera were of 100% sensitivity, with a 98% specificity for BCCA and CFA, and a 100% specificity for CASA. The application of these selective agars for Campylobacter spp. enumeration in comparison to the conventional agars, modified charcoal cefoperazonedeoxycholate agar (mCCDA) and Campy-Cefex (CCA) was examined using Campylobacter jejuni and Campylobacter coli inoculated samples. From C. jejuni inoculated samples, recovery on BCCA was significantly greater than other media (p<0.05). Recovery on CASA was not significantly different from mCCDA and CCA (p>0.05). With C. coli inoculated samples, recovery was significantly greater on BCCA and CASA than with other media (p<0.05). The recovery of both C. jejuni and C. coli from inoculated samples with CFA was significantly less than with other media (P<0.05). CASA was able to effectively inhibit and differentiate Campylobacter spp. from background microflora while false positive organisms occurred with BCCA and CFA. An examination of 483 randomly selected suspect Campylobacter colonies from naturally contaminated samples demonstrated a colony confirmation rate for CCA, CFA, BCCA, mCCDA, and CASA, of 84%, 87%, 88%, 90%, and 100%, respectively. The media evaluated present an alternative to conventional selective agars for the identification and enumeration of thermotolerant Campylobacter spp. from samples of poultry origin through the farm to fork continuum.


CD8+ T-cell immunosurveillance constrains lymphoid premetastatic myeloid cell accumulation.
Increasing evidence suggests that premetastatic niches, consisting mainly of myeloid cells, provide microenvironment critical for cancer cell recruitment and survival to facilitate metastasis. While CD8(+) T cells exert immunosurveillance in primary human tumors, whether they can exert similar effects on myeloid cells in the premetastatic environment is unknown. Here, we show that CD8(+) T cells are capable of constraining premetastatic myeloid cell accumulation by inducing myeloid cell apoptosis in C57BL/6 mice. Ag-specific CD8(+) T-cell cytotoxicity against myeloid cells in premetastatic lymph nodes is compromised by Stat3. We demonstrate here that Stat3 ablation in myeloid cells leads to CD8(+) T-cell activation and increased levels of IFN-γ and granzyme B in the premetastatic environment. Furthermore, Stat3 negatively regulates soluble Ag cross-presentation by myeloid cells to CD8(+) T cells in the premetastatic niche. Importantly, in tumor-free lymph nodes of melanoma patients, infiltration of activated CD8(+) T cells inversely correlates with STAT3 activity, which is associated with a decrease in number of myeloid cells. Our study suggested a novel role for CD8(+) T cells in constraining myeloid cell activity through direct killing in the premetastatic environment, and the therapeutic potential by targeting Stat3 in myeloid cells to improve CD8(+) T-cell immunosurveillance against metastasis.


[Childhood cancer: a comparative analysis of incidence, mortality, and survival in Goiania (Brazil) and other countries].
Analysis of cancer incidence, mortality, and survival rates can yield geographic and temporal trends that are useful for planning and evaluating health interventions. This article reviews cancer incidence and mortality rates and respective trends around the world in children under 15 years old, as well as their 5-year survival rates in developed and developing countries. We conclude that even though increasing or stable childhood cancer incidence rates and decreasing mortality rates have been observed in developed countries, the trends remain unknown in developing countries. Data from the city of Goiania, Brazil, show stable childhood cancer incidence and mortality rates. Five-year survival rates (48%) in Goiania are similar to those seen in underdeveloped regions and lower than those reported in developed countries (64-70%).


Sound speeds and laser induced damage in polystyrene.
Sound speeds for gigahertz frequencies were measured as a function of temperature from 25 degrees C to 110 degrees C in clean samples of polystyrene by stimulated Brillouin scattering. The effect on the sound speeds of annealing the polymer was shown. The glass transition temperature was determined to be 95 degrees C from which the number averaged molecular weight was found. Damage observations were made on the prepared sample and compared with those made on commercial samples.


Evaluation of in vitro urease and lipoxygenase inhibition activity of weight reducing tablets.
Enzyme inhibition is a significant part of research in pharmaceutical field in view of the fact that these studies have directed to the innovations of drugs having remarkable performance in diverse physiological conditions. The present study was aimed to assess urease and lipoxygenase inhibitory activity of weight reducing tablets. For evaluating the urease activity indophenol method was employed using Thiourea as the model urease inhibitor. The lipoxygenase inhibition was evaluated by measuring the hydroperoxides produced in lipoxygenation reaction using a purified lipoxygenase with lionoleic acid as substrate. When formulation of the weight reducing tablets was compared at various concentrations (50, 100 and 500µg/ml). The antiurease activity and lipoxygenase inhibition activity increased in a dose dependent manner. The formulations under test have an excellent antiurease and lipoxygenase inhibition potential and prospective to be used in the cure of a variety of complications associated with the production of urease and lipoxygenase enzymes.


Ambiguity of Whole Body PET CT Scans in Diagnosis of Co-existing Tuberculosis and Malignancy: Is Histopathological Confirmation Mandatory?
Whole body PET CT is an important investigation tool in malignancy patients and helps in ascertaining the metabolic activity and exact stage of the disease. However, like any other investigation, false positive results do exist and certain diseases other than cancer may show increased uptake. Hence, a careful evaluation of PET CT and clinical correlation in malignancy patients is a must to accomplish the suitable treatment. In this retrospective observational study, seven cases of cancer with concomitant tuberculosis were included. All the patients were proven malignancy patients with advanced or metastatic stage. On clinical suspicion, a tissue diagnosis was obtained which led to change in staging as well as management of the patients. Seven patients were having primary diagnosis of carcinoma breast, carcinoma esophagus, coepidermoid carcinoma of submandibular salivary gland, carcinoma tongue, squamous cell carcinoma skin, carcinoma cervix and carcinoma endometrium. They showed FDG uptake at distant sites leading to upstaging of disease. On histopathological examination, lymph nodal mass reported granulomatous lymphadenitis, leading to change of overall staging and management of the patients. Whole Body PET CT scan may produce false positive results and upstage the disease. It should be evaluated and interpreted with caution in cases of doubtful findings and any abnormal FDG accumulation in PET CT scan at unusual locations should be evaluated carefully and confirmed histopathologically.


Mandibular first molar with single root and single root canal.
Mandibular molars demonstrate considerable anatomic complexities and abnormalities with respect to number of roots and root canals. Clinicians should be aware that there is a possibility of the existence of a fewer number of roots and root canals than the normal root canal anatomy. Mandibular first molar with a single root and single canal was diagnosed with the aid of dental operating microscope and multiple angled radiographs. This case report presents a rare case of successful endodontic management of mandibular first molar with a single root and root canal.


Antipsychotics in the treatment of schizophrenia: an overview.
Schizophrenia is characterized by positive, negative, cognitive, disorganization, and mood symptoms. Antipsychotics are the mainstay in the pharmacologic treatment of schizophrenia. Findings concerning efficacy for positive symptoms and disorganization suggest no consistent differences among available antipsychotics, with the exception of clozapine's superior efficacy for treatment-resistant schizophrenia. Efficacy for negative, depressive, and cognitive symptoms appears to be determined by (1) the extent to which reduction in positive symptoms brings about improvement in these other domains and (2) the extent to which extrapyramidal side effects (EPS) and anticholinergic effects (of the antipsychotic and of agents used to treat EPS) exacerbate them. Thus, the ability of antipsychotics to produce a potent antipsychotic effect without EPS and need for concomitant anticholinergic therapy yields multiple therapeutic benefits. In contrast to their broadly similar efficacy, antipsychotics differ markedly in their propensity to cause various adverse effects. Although second-generation antipsychotics (SGAs) have generally been believed to be associated with a lower risk of EPS but a higher risk of metabolic adverse effects than first-generation agents (FGAs), the substantial variation in these and other side effects among agents within both classes indicates that it is not clinically useful to make a categorical distinction between FGAs and SGAs. Choice of antipsychotic medication should be based on individual preference, prior treatment response and side effect experience, medical history and risk factors, and adherence history, with side effect profile a major determinant of antipsychotic choice.


[AIDS and forensic medicine. I. The framework of the debate].
The ethical debate regarding the AIDS is very rich both at the theoretical and practical level, but--unlike what it is happening for other sectors, e.g. the euthanasia--these two aspects are integrated, shaping a true interdisciplinary job of ethical evaluation, in which clinicians, medical examiners, ethicists, nurses, clinical psychologists, economists and politicians are met. The utilized methodology will be to identify the human act in the light of the patient's good and the common good of the society. These are strong references and broadly shared in general sense, but they become problematic if we want to identify, and we should have to do it, the contents of such "goods". The authors intend to appraise the quality of a Centre for Research and Healthcare for AIDS patients, also considering the "performance measures".


Gastrointestinal and metabolic effects of methylxanthines.
This chapter has covered a wide range of different actions of methylxanthines. They are able to slightly reduce the tone of the lower esophageal sphincter. This is of little concern in the normal individual, but in patients with a reduced initial tone it might lead to heartburn. Coffee intake has been associated with gastritis, but the role of methylxanthines in this effect is obscure. High doses of methylxanthines are also known to be emetic. Practically every function in the intestine can be influenced by high doses of methylxanthines, but the mechanisms involved and the biological significance remain largely obscure. Although in vitro studies with high doses of methylxanthines have demonstrated effects on secretion from salivary glands and exocrine pancreas, there is little evidence that this is clinically important in man. There is also small effects on insulin, glucagon, and TSH secretion. There is a consistent effect on fatty acid mobilization from adipose tissue, which may be of importance, eg, by improving physical performance and by increasing the overall metabolic rate. There is also some evidence for long-term effects on fat depots. By contrast, the effects on carbohydrate metabolism are much less prominent and reproducible, and may to some extent be secondary to altered lipid metabolism. Despite more than a century of effort to elucidate the actions of methylxanthines in man, one of the major conclusions to be drawn is that there is a need for further studies. In view of the newer ideas about the mechanism of action of caffeine and other methylxanthines, careful studies, especially of long-term effects of methylxanthines on several aspects of gastrointestinal function, on calcium homeostasis, on body composition, and on physical performance, would be desirable.


Cross-talk of cholinergic and β-adrenergic receptor signalling in chronic myeloid leukemia K562 cells.
In many studies on breast, skin and intestinal cancers, β-adrenergic receptor antagonists have been shown to inhibit cell proliferation and angiogenesis and increase apoptosis in cancers. Carbachol inhibits chronic myeloid leukaemia K562 cell proliferation. Beta-blockers are known to inhibit cell progression. The aim of this study is to explain the mechanism of action of β-adrenergic receptors agonists and antagonists on apoptosis in chronic myeloid leukaemia cells. We tried to determine the effect of combined treatment of β-adrenergic and cholinergic drugs on adrenergic β1 and β2 gene expression, cell proliferation and apoptosis in chronic myeloid leukaemia K562 cells. Cell proliferation was evaluated by the 5-bromo-2-deoxy-uridine (BrdU) incorporation kit. Caspase 3, 8, 9 activities were measured by the caspase assay kit. Protein expression level was detected by western blotting. We found that exposure to propranolol either by combination with carbachol facilitates additive effects on inhibition of caspase 3 and 8 expression in chronic myeloid leukaemia K562 cells. However, caspase 9 expression level was increased by propranolol alone or with propranolol and carbachol combination. The combined therapy of cholinergic and adrenergic receptor drugs will decrease cell proliferation in K562 cells. This decrease in cell proliferation may be mediated by the mitochondrial-dependent intrinsic apoptosis pathway.


Dioszegia zsoltii sp. nov., a new ballistoconidium-forming yeast species with two varieties.
As a result of conventional characterization of yeasts isolated from various plant leaves collected in Yunnan, China, six ballistoconidium-forming strains with orange-colored colonies were grouped together. Molecular phylogenetic analysis based on 18S rDNA sequencing showed that two representative strains of this group of yeasts, CH 2.068 and CH 2.497, were closely related to the species in the genus Dioszegia and had signature sequences typical of this genus. However, the six strains from Yunnan differed from the described Dioszegia species remarkably (14.5-17.7% nucleotide divergences) in the ITS (internal transcribed spacer) region sequences, which indicated that they represent a distinct species. Furthermore, among the six strains studied, the ITS region sequence comparison allowed the recognition of two subgroups represented by CH 2.068 and CH 2.497, which differ from each other in three bases in the ITS 2 region. DNA-DNA relatedness revealed that the two subgroups represent two varieties of a new species in the genus Dioszegia, for which Dioszegia zsoltii sp. nov. var. zsoltii and Dioszegia zsoltii var. yunnanensis var. nov. are proposed.


Computed tomographic, magnetic resonance, and monoclonal antibody imaging of endocrine tumors.
Recent advances in diagnostic imaging with computed tomography, magnetic resonance imaging, and monoclonal antibody imaging in endocrine tumor evaluation are reviewed. Computed tomography is a mature technology whose role has not changed recently. Magnetic resonance imaging is continuing to advance in scan techniques, scan time reduction, and use of intravenous contrast agents; its future role on a routine basis may allow it to supplant computed tomography in endocrine tumor identification. Monoclonal antibody imaging has not yet proven to be as reliably diagnostic for tumor identification as is computed tomography, but continuing technical advances predict an advancing role for diagnosing endocrine tumors with this modality.


Interaction of Human Salivary Gland Epithelial Cells with B Lymphocytes: Implications in the Pathogenesis of Sjögren's Syndrome.
Sjögren's syndrome (SS) is characterized by the aberrant activation of B-cells in both the target organs of autoimmune responses, such as the exocrine glands and the periphery. Furthermore, SS is strongly associated with the development of B-cell non-Hodgkin lymphomas, which are considered to result from chronic aberrant activation of B-cells. Disturbances of the minor salivary gland (MSG) infiltrating and peripheral B-cells subpopulations have been described in SS patients; however, the underlying mechanisms have not been uncovered. SG epithelial cells (SGECs) play a key role in the development and organization of MSG lymphocytic infiltrates in SS patients. SGECs are suitably equipped to mediate the recruitment, activation, and differentiation of immune cells in SS, including CD4+-T cells. B-cell activating factor (BAFF) secretion by SGECs suggests that they can also fruitfully interact with B-cells and mediate their activation, differentiation, and disturbed subpopulations in SS. The effect of SGECs in the activation and differentiation of naïve peripheral B-cells, as this attested by phenotypical flow cytometric and cytokine production analyses, is under investigation in the current proposal. This approach is expected to enlighten the mechanisms underlying the aberrant activation and differentiation of B cells in SS and the discovery of novel therapeutic targets for its reversal.


High-rate synthetic aperture communications in shallow water.
Time reversal communication exploits spatial diversity to achieve spatial and temporal focusing in complex ocean environments. Spatial diversity can be provided easily by a vertical array in a waveguide. Alternatively, spatial diversity can be obtained from a virtual horizontal array generated by two elements, a transmitter and a receiver, due to relative motion between them, referred to as a synthetic aperture. This paper presents coherent synthetic aperture communication results from at-sea experiments conducted in two different frequency bands: (1) 2-4 kHz and (2) 8-20 kHz. Case (1) employs binary-phase shift-keying modulation, while case (2) involves up to eight-phase shift keying modulation with a data rate of 30 kbits/s divided by the number of transmissions (diversity) to be accumulated. The receiver utilizes time reversal diversity combining followed by a single channel equalizer, with frequent channel updates to accommodate the time-varying channel due to coupling of space and time in the presence of motion. Two to five consecutive transmissions from a source moving at 4 kts over 3-6 km range in shallow water are combined successfully after Doppler compensation, confirming the feasibility of coherent synthetic aperture communications using time reversal.


[Fatal cases of poisonings among drug addicts in the county of Funen in 1993].
This study includes death from poisoning among drug addicts in 1993 in the county of Funen, in all 24. The development during the last five years shows an increase, especially in the largest city in the county. The drug addicts have several problems, and several of them were well-known in the social welfare system or by the police. Half of the drug addicts had received treatment for their abuse and three persons were receiving treatment at the time of their death. A few--primarily among the youngest--had only used drugs for a short time while one third had abused drugs for several years. The greater part of the deaths were caused by heroin, which is found in different concentrations in the illegal market. Five of the dead persons had just been released from prison and three people had just left 24-hour care centres when they were found dead. Co-operation between the various, treating authorities has to be given a high priority.


Occupational exposures and non-Hodgkin's lymphoma: Canadian case-control study.
The objective was to study the association between Non-Hodgkin's Lymphoma (NHL) and occupational exposures related to long held occupations among males in six provinces of Canada. A population based case-control study was conducted from 1991 to 1994. Males with newly diagnosed NHL (ICD-10) were stratified by province of residence and age group. A total of 513 incident cases and 1506 population based controls were included in the analysis. Conditional logistic regression was conducted to fit statistical models. Based on conditional logistic regression modeling, the following factors independently increased the risk of NHL: farmer and machinist as long held occupations; constant exposure to diesel exhaust fumes; constant exposure to ionizing radiation (radium); and personal history of another cancer. Men who had worked for 20 years or more as farmer and machinist were the most likely to develop NHL. An increased risk of developing NHL is associated with the following: long held occupations of faer and machinist; exposure to diesel fumes; and exposure to ionizing radiation (radium). The risk of NHL increased with the duration of employment as a farmer or machinist.


Hepatitis B virus and hepatocellular carcinoma: molecular biology and mechanistic considerations.
The question of whether HBV causes HCC has to date best been answered by epidemiologic studies, in particular prospective analysis such as the ongoing study in Taiwan. The mechanism whereby HBV may cause HCC by genetic or epigenetic means, acting alone or in concert with other agents, is still moot . To date, studies of HBV gene expression have not shown the presence of a transforming gene or an oncogene associated with this virus. The finding of integrated HBV DNA in most HCC of carriers is highly suggestive of a causal role of the virus in the pathogenesis of neoplasia. In order to be more certain, it will be necessary to show that expression of integrated HBV genes or of cellular genes, as a result of HBV infection, causes neoplastic transformation of cells. Failure to date to demonstrate that HBV DNA induces neoplastic transformation of eukaryotic cells in culture may be simply due to an inadequate experimental model. The majority of these experiments have used fibroblasts or monkey kidney cells as the recipient cell, whereas cultured human hepatocytes might be more suitable. Whatever role HBV eventually is shown to have in the pathogenesis of HCC, molecular biologic techniques will have in great measure contributed to that knowledge. The use of these powerful new methods will permit studies of the replication of HBV and possible elucidation of how this virus affects the hepatocyte during persistent infection and will in time lead to a better understanding of cell and molecular events leading to development of hepatic malignancy.


FK506 Binding Protein 10 Is Overexpressed and Promotes Renal Cell Carcinoma.
FK506 binding proteins (FKBPs) function as oncogenes or tumor suppressors by interacting with steroid hormone receptors, kinases, or other cellular factors in addition to intracellular ligands FK506 and rapamycin. In this study, we aimed at evaluating the expression and function of FKBPs in renal cell carcinoma (RCC). Thirty-four RCC specimens were analyzed by whole transcriptome sequencing. Small interfere RNA was employed to knockdown FKBP10 in 786-O and A-704 cells, and cell proliferation, cell cycle progression, invasion and migration were evaluated. FKBP10 was different from other members of FKBPs with most significant upregulation in almost all RCC specimens, compared to normal mucosa. FKBP10 expression was high in additional 38 RCC specimens and RCC cell lines compared to paired non-tumor tissues and normal renal tubule cells. FKBP10 knockdown led to cell cycle arrest at G0/G1 phase, and reduced cell proliferation, invasion, and migration in 786-O and A-704 cells. In addition, heat shock protein 90 was significantly downregulated after FKBP10 knockdown. FKBP10 is overexpressed and promotes RCC and is a new promising biomarker and therapy target for RCC.


Relaxation and hypnosis in pediatric dental patients.
Relaxation and hypnosis are methods which, may solve the problem of extreme dental anxiety, when all other methods, behavioral or pharmacological may not be used. A simple definition of hypnosis is suggestion and repetition. Suggestion is the process whereby an individual accepts a proposition put to him by another, without having the slightest logical reason for doing so. Relaxation is one method of inducing hypnosis. A case of using hypnosis on an 11-year-old boy is described.


Hydrocephalus and neurocysticercosis: cases illustrative of three distinct mechanisms.
Cysticercosis is the most frequent parasitic infection of the nervous system. Most lesions are intracranial, and spinal involvement is rare. We describe here in two cases of neurocysticercosis (NCC) in the brain and one in the spinal cord that illustrate three distinct mechanisms leading to symptomatic acute hydrocephalus. Hydrocephalus was related to intracranial NCC in two of them. In the first case the hydrocephalus was due to an extensive arachnoiditis to the craniocervical junction, while in the second it was caused by obstruction of Magendie's foramen in the fourth ventricle by the scolex of Taenia solium. For the third patient, hydrocephalus revealed cysticercosis of the cauda equina due to the scolex. NCC should be considered as a possible diagnosis for patients suffering from hydrocephalus when they originate from or have traveled in endemic areas, MRI of the spine is mandatory to search for intraspinal lesions.


Cord blood stem cell banking and transplantation.
Cord blood banking for the purpose of stem cell transplantation is a rapidly growing area of medical interest. Based on the fact that cord blood contains large numbers of stem and progenitor cells, transplantation of cord blood for marrow reconstitution was first attempted in 1988. The success of this initial transplant between related donor and patient rapidly led to the establishment of efforts to collect, store and eventually transplant unrelated cord blood samples. A collection and storage program established by the New York Blood Center has led to more than 400 such transplants. The results demonstrate acceptable rates of engraftment and little graft-versus-host disease compared to the results employing adult marrow. As a consequence of these observations, considerable effort is being made to establish cord blood banks around the world.


Inspiratory and expiratory effects of nasal breathing.
The purpose of the present study was to assess quantitatively the nasal valve area during normal inspiratory and expiratory maneuvers. The pressure-flow technique of Warren was used to estimate nasal size in 15 adult subjects who had no previous history of nasal surgery or abnormality. Cross-sectional size of the nasal airway was also assessed (1) after insertion of tubing to eliminate alar effects, (2) after administration of 0.1% Otrivin decongestant to eliminate mucosal effects, and (3) by blocking each nostril individually. Mean areas of 0.63 cm2 +/- 0.17 during inspiration and 0.56 cm2 +/- 0.14 during expiration. This difference is statistically significant (less than 0.01) and the effect was maintained under conditions of occlusion of either nostril, insertion of tubing, and administration of Otrivin. These findings suggest that the nasal valve acts as a respiratory brake during expiration possibly to allow adequate time for gas exchange at the alveoli.


Lanthanide(III) complexes that contain a self-immolative arm: potential enzyme responsive contrast agents for magnetic resonance imaging.
Enzyme-responsive MRI-contrast agents containing a "self-immolative" benzylcarbamate moiety that links the MRI-reporter lanthanide complex to a specific enzyme substrate have been developed. The enzymatic cleavage initiates an electronic cascade reaction that leads to a structural change in the Ln(III) complex, with a concomitant response in its MRI-contrast-enhancing properties. We synthesized and investigated a series of Gd(3+) and Yb(3+) complexes, including those bearing a self-immolative arm and a sugar unit as selective substrates for β-galactosidase; we synthesized complex LnL(1), its NH(2) amine derivatives formed after enzymatic cleavage, LnL(2), and two model compounds, LnL(3) and LnL(4). All of the Gd(3+) complexes synthesized have a single inner-sphere water molecule. The relaxivity change upon enzymatic cleavage is limited (3.68 vs. 3.15 mM(-1) s(-1) for complexes GdL(1) and GdL(2), respectively; 37 °C, 60 MHz), which prevents application of this system as an enzyme-responsive T(1) relaxation agent. Variable-temperature (17)O NMR spectroscopy and (1)H NMRD (nuclear magnetic relaxation dispersion) analysis were used to assess the parameters that determine proton relaxivity for the Gd(3+) complexes, including the water-exchange rate (k(ex)(298), varies in the range 1.5-3.9×10(6) s(-1)). Following the enzymatic reaction, the chelates contain an exocyclic amine that is not protonated at physiological pH, as deduced from pH-potentiometric measurements (log K(H)=5.12(±0.01) and 5.99(±0.01) for GdL(2) and GdL(3), respectively). The Yb(3+) analogues show a PARACEST effect after enzymatic cleavage that can be exploited for the specific detection of enzymatic activity. The proton-exchange rates were determined at various pH values for the amine derivatives by using the dependency of the CEST effect on concentration, saturation time, and saturation power. A concentration-independent analysis of the saturation-power-dependency data was also applied. All these different methods showed that the exchange rate of the amine protons of the Yb(III) complexes decreases with increasing pH value (for YbL(3), k(ex)=1300 s(-1) at pH 8.4 vs. 6000 s(-1) at pH 6.4), thereby resulting in a diminution of the observed CEST effect.


Worker heat stress prevention and work metabolism estimation: comparing two assessment methods of the heart rate thermal component.
The heart rate thermal component ( ΔHRT ) can increase with body heat accumulation and lead to work metabolism (WM) overestimation. We used two methods (VOGT and KAMP) to assess ΔHRT of 35 forest workers throughout their work shifts, then compared ΔHRT at work and at rest using limits of agreement (LoA). Next, for a subsample of 20 forest workers, we produced corrected WM estimates from ΔHRT and compared them to measured WM. Although both methods produced significantly different ΔHRT time-related profiles, they yielded comparable average thermal cardiac reactivity (VOGT: 24.8 bpm °C-1; KAMP: 24.5 bpm °C-1), average ΔHRT (LoA: 0.7 ± 11.2 bpm) and average WM estimates (LoA: 0.2 ± 3.4 ml O2 kg-1min-1 for VOGT, and 0.0 ± 5.4 ml O2 kg-1min-1 for KAMP). Both methods are suitable to assess heat stress through ΔHRT and improve WM estimation. Practitioner summary: We compared two methods for assessing the heart rate thermal component ( ΔHRT ), which is needed to produce a corrected HR profile for estimating work metabolism (WM). Both methods yielded similar ΔHRT estimates that allowed accurate estimations of heat stress and WM at the group level, but they were imprecise at the individual level. Abbreviations: AIC: akaike information criterion; bpm: beats per minute; CI: confidence intervals; CV: coefficient of variation in %; CV drift: cardiovascular drift; ΔHRT: the heart rate thermal component in bpm; ΔHRT: the heart rate thermal component in bpm; ΔΔHRT: variation in the heart rate thermal component in bpm; ΔTC: variation in core body temperature in °C; HR: heart rate in bpm; HRmax: maximal heart rate in bpm; Icl: cloting insulation in clo; KAMP: Kampmann et al. (2001) method to determe ΔHRT; LoA: Limits of Agreement; PMV-PPD: the Predicted Mean Vote and Predicted Percentage Dissatisfied; PHS: Predicted Heat Strain model; RCM: random coefficients model; SD: standard deviation; TC: core body temperature in °C; TCR: thermal cardiac reactivity in bpm °C-1; τΔHRT: rate of change in the heart rate thermal component in bpm min-1; τTC: rate of change in core body temperature in °C min-1; tα,n-1: Student's t statistic with level of confidence alpha and n-1 degrees of freedom; TWL: Thermal Work Limit model; V̇O2 : oxygen consumption in ml O2 kg-1 min-1; V̇O2 max: maximal oxygen consumption in ml O2 kg-1 min-1; VOGT: Vogt et al. (1973) method to determine ΔHRT; WBGT: Wet-Bulb Globe Temperature in °C; WM: work metabolism.


Molecular mechanisms of thrombin function.
The discovery of thrombin as a Na(+)-dependent allosteric enzyme has revealed a novel strategy for regulating protease activity and specificity. The alllosteric nature of this enzyme influences all its physiologically important interactions and rationalizes a large body of structural and functional information. For the first time, a coherent mechanistic framework is available for understanding how thrombin interacts with fibrinogen, thrombomodulin and protein C, and how Na+ binding influences the specificity sites of the enzyme. This information can be used for engineering thrombin mutants with selective specificity towards protein C and for the rational design of potent active site inhibitors. Thrombin also serves as a paradigm for allosteric proteases. Elucidation of the molecular basis of the Na(+)-dependent allosteric regulation of catalytic activity, based on the residue present at position 225, provides unprecedented insights into the function and evolution of serine proteases. This mechanism represents one of the simplest and most important structure-function correlations ever reported for enzymes in general. All vitamin K-dependent proteases and some complement factors are subject to the Na(+)-dependent regulation discovered for thrombin. Na+ is therefore a key factor in the activation of zymogens in the coagulation and complement systems.


Regulation of transport processes across the tonoplast.
In plants, the vacuole builds up the cellular turgor and represents an important component in cellular responses to diverse stress stimuli. Rapid volume changes of cells, particularly of motor cells, like guard cells, are caused by variation of osmolytes and consequently of the water contents in the vacuole. Moreover, directed solute uptake into or release out of the large central vacuole allows adaptation of cytosolic metabolite levels according to the current physiological requirements and specific cellular demands. Therefore, solute passage across the vacuolar membrane, the tonoplast, has to be tightly regulated. Important principles in vacuolar transport regulation are changes of tonoplast transport protein abundances by differential expression of genes or changes of their activities, e.g., due to post-translational modification or by interacting proteins. Because vacuolar transport is in most cases driven by an electro-chemical gradient altered activities of tonoplast proton pumps significantly influence vacuolar transport capacities. Intense studies on individual tonoplast proteins but also unbiased system biological approaches have provided important insights into the regulation of vacuolar transport. This short review refers to selected examples of tonoplast proteins and their regulation, with special focus on protein phosphorylation.


'Heads held high': an exploratory study of legal highs in pre-legislation Ireland.
The research aimed to present a unique 'snapshot' of legal psychoactive drug use prior to legislative control in Ireland, in relation to the types of products used; sourcings; consumptive practices and particular social settings for use; gauging of dosage; licit and illicit drug transitions, individualisation of drug decision-making and experiences; and future intentions regarding drug switching post legislation. Semi-structured in depth interviews (n = 32) were conducted with adults aged 18-33 years who had used legal highs in the 6 months prior to fieldwork. The findings indicate some support for 'differentiated' displacement consumptive patterns between illegal and legal drugs, with user pathways grounded in 'legal high' availability; perceived user effect, safety, legality, quality and price. Mephedrone emerged as most popular drug of choice. Internet sales, stockpiling and diversion of previously 'legal highs' onto the illegal street drug market remain of concern, against a background of emerging new designer drugs in Ireland.


Prediction of aluminum, uranium, and co-contaminants precipitation and adsorption during titration of acidic sediments.
Batch and column recirculation titration tests were performed with contaminated acidic sediments. A generic geochemical model was developed combining precipitation, cation exchange, and surface complexation reactions to describe the observed pH and metal ion concentrations in experiments with or without the presence of CO2. Experimental results showed a slow pH increase due to strong buffering by Al hydrolysis and precipitation and CO2 uptake. The cation concentrations generally decreased at higher pH than those observed in previous tests without CO2. Using amorphous Al(OH)3 and basaluminite precipitation reactions and a cation exchange selectivity coefficient K(Na\Al) of 0.3, the model approximately described the observed (1) pH titration curve, (2) Ca, Mg, and Mn concentration by cation exchange, and (3) U concentrations by surface complexation with Fe hydroxides at pH < 5 and with liebigite (Ca2UO2(CO3)3·10H2O) precipitation at pH > 5. The model indicated that the formation of aqueous carbonate complexes and competition with carbonate for surface sites could inhibit U and Ni adsorption and precipitation. Our results suggested that the uncertainty in basaluminite solubility is an important source of prediction uncertainty and ignoring labile solid phase Al underestimates the base requirement in titration of acidic sediments.


Electroosmotic flow rectification in pyramidal-pore mica membranes.
We demonstrate here a new electrokinetic phenomenon, Electroosmotic flow (EOF) rectification, in synthetic membranes containing asymmetric pores. Mica membranes with pyramidally shaped pores prepared by the track-etch method were used. EOF was driven through these membranes by using an electrode in solutions on either side to pass a constant ionic current through the pores. The velocity of EOF depends on the polarity of the current. A high EOF velocity is obtained when the polarity is such that EOF is driven from the larger base opening to the smaller tip opening of the pore. A smaller EOF velocity is obtained when the polarity is reversed such that EOF goes from tip to base. We show that this rectified EOF phenomenon is the result of ion current-rectification observed in such asymmetric-pore membranes.


Protection against lyme disease spirochete transmission provided by prompt removal of nymphal Ixodes scapularis (Acari: Ixodidae).
Public health recommendations for Lyme disease prevention generally include daily tick checks and prompt removal of attached ticks as a means of decreasing the risk of acquiring Lyme disease in highly endemic regions. In the current study, we determined whether crushing nymphal ticks during removal with forceps increased the risk of B. burgdorferi transmission, what degree of protection from transmission of B. burgdorferi was provided by removal of nymphal Ixodes scapularis Say at specific intervals, and whether commercial devices marketed for tick removal worked when tested against nymphal I. scapularis. Both removal via gentle pressure (26% transmission) or crushing the tick (30% transmission) caused a significant decrease in transmission as compared with the sham control (70% transmission). The degree of protection provided via tick removal decreased steadily up to 60 h of attachment; between 60 and 66 h, a dramatic falloff in protection occurred to the point where no protection was observed at 66 h. Finally, commercial tick removal devices varied widely in their efficacy for the removal of attached nymphal I. scapudaris.


[A case of pulmonary plasma cell granuloma with a cavity].
Plasma cell granuloma of the lung is an uncommon and non-malignant neoplasm that may present difficulties in both diagnosis and management. We report a 52-year-old male who was admitted to our hospital due to fever and an abnormal shadow on chest roentgenography. Chest computed tomography revealed a tumor shadow with a cavity in the left upper lobe. However, neither bronchofiberscopy nor serum examinations suggested a diagnosis. Video-assisted thoracoscopic surgery (VATS) was performed and postoperative pathological examination of the resected specimen showed plasma cell granuloma. The postoperative course was uneventful. No recurrence was observed 10 months after the operation. As plasma cell granuloma of the lung is histologically benign, surgery should be performed to preserve the maximal residual lung with no lesion. VATS is the method of choice for treatment of pulmonary plasma cell granuloma.


dCas9 binding inhibits the initiation of base excision repair in vitro.
Cas9 targets DNA during genome editing by forming an RNA:DNA heteroduplex (R-loop) between the Cas9-bound guide RNA and the targeted DNA strand. We have recently demonstrated that R-loop formation by catalytically inactive Cas9 (dCas9) is inherently mutagenic, in part, by promoting spontaneous cytosine deamination within the non-targeted single-stranded DNA of the dCas9-induced R-loop. However, the extent to which dCas9 binding and R-loop formation affect the subsequent repair of uracil lesions or other damaged DNA bases is unclear. Here, we show that DNA binding by dCas9 inhibits initiation of base excision repair (BER) for uracil lesions in vitro. Our data indicate that cleavage of uracil lesions by Uracil-DNA glycosylase (UDG) is generally inhibited at dCas9-bound DNA, in both the dCas9:sgRNA-bound target strand (TS) or the single-stranded non-target strand (NT). However, cleavage of a uracil lesion within the base editor window of the NT strand was less inhibited than at other locations, indicating that this site is more permissive to UDG activity. Furthermore, our data suggest that dCas9 binding to PAM sites can inhibit UDG activity. However, this non-specific inhibition can be relieved with the addition of an sgRNA lacking sequence complementarity to the DNA substrate. Moreover, we show that dCas9 binding also inhibits human single-strand selective monofunctional uracil-DNA glycosylase (SMUG1). Structural analysis of a Cas9-bound target site subsequently suggests a molecular mechanism for BER inhibition. Taken together, our results imply that dCas9 (or Cas9) binding may promote background mutagenesis by inhibiting the removal of DNA base lesions by BER.


Hold or fold--proteins in advanced heart failure and myocardial recovery.
Advanced heart failure (AHF) describes the subset of heart failure patients refractory to conventional medical therapy. For some AHF patients, the use of mechanical circulatory support (MCS) provides an intermediary "bridge" step for transplant-eligible patients or an alternative therapy for transplant-ineligible patients. Over the past 20 years, clinical observations have revealed that approximately 1% of patients with MCS undergo significant reverse remodeling to the point where the device can be explanted. Unfortunately, it is unclear why some patients experience durable, sustained myocardial remission, while others redevelop heart failure (i.e. which hearts "hold" and which hearts "fold"). In this review, we outline unmet clinical needs related to treating patients with MCS, provide an overview of protein dynamics in the reverse-remodeling process, and propose specific areas where we expect MS and proteomic analyses will have significant impact on our understanding of disease progression, molecular mechanisms of recovery, and provide new markers with prognostic value that can positively impact patient care. Complimentary perspectives are provided with the goal of making this important topic accessible and relevant to both a clinical and basic science audience, as the intersection of these disciplines is required to advance the field.


Evaluation of mare oocyte collection methods and stallion sperm penetration of zona-free hamster ova.
Comparisons were made between 2 methods of oocyte recovery from the ovarian follicles of slaughtered mares: 500 oocytes (3 per mare) were obtained by aspiration of follicular fluid from ovaries of 162 mares, and 120 oocytes (8 per mare) by isolation and rupture of follicles from ovaries of 14 mares. In the oocytes recovered after rupture of follicles, 89.2% were morphologically unchanged, in comparison to 29.3% obtained by aspiration of follicular fluid. Stallion spermatozoa capacitated in vitro were tested on zona-free hamster oocytes. The stallion spermatozoa were washed in TCM-199 and preincubated for 4-5 h at a concentration of 0.5-1.0 x 10(9)/ml. Of the 305 hamster oocytes fertilized by spermatozoa obtained from 8 stallions, 77.8% penetration was confirmed on the basis of the presence of enlarged heads of spermatozoa and male pronuclei with their corresponding tails. Spermatozoa from one of the stallions were tested 10 times, 8 months later. The percentage of penetrated oocytes averaged 52.8% (39.1-76.9%). In the control group of oocytes preincubated in the absence of spermatozoa, spontaneous activation and female pronuclei were found in 12 out of a total of 57.


[Surgical and experimental-biological aspects of inguinal hernia].
In experiment on 57 animals the method of plasty of anterior wall of inguinal channel by forming of the aponeurosis of m. abdominis obliqus ext. and suturing together the aponeurotic edges was simulated. The results of surgical correction of inguinal hernia in 257 patients were analysed. The correlational connection of immunological changes in organism with the degree of destructive changes of hematotesticular barrier (HTB) and spermatogenic epithelium was established. Considering the testicle autoimmunity the application of protective operative methods of pharmacological defense of HTB and spermatogenic epithelium are proposed.


[Clinical therapeutic effect of point-injection combined with body acupuncture on prementstrual tension syndrome].
To compare clinical therapeutic effects of acupoint-injection combined with body acupuncture and medication on premenstrual tension syndrome, and probe to the best therapy for this disease. One hundred and two cases were randomly divided into an acupoint-injection plus body acupuncture group (treatment group) and a medication group (control group). The treatment group were treated with injection of Huangqi Injection into Zusanli (ST 36), Sanyinjiao (SP 6), and acupuncture at Hegu (LI 4), Taichong (LR 3), Guanyuan (CV 4), Qihai (CV 6), Taiyang (EX-HN5), Fengchi (GB 20) 10 days before menstruation, once every three days; the control group were treated by oral administration of diazepam and oryzanol at routine dose 10 days before menstruation until stopping of menstrual. Their therapeutic effects were compared after treatment for 3 menstrual cycles. The total effective rate was 92.6% in the treatment group and 75.0% in the control group with a significant difference between the two groups (P<0.05). The clinical therapeutic effect of the acupoint-injection combined with body acupuncture is better than that of the medication on premenstrual tension syndrome.


Prevalence and Extent of Gingival Recession in a National Sample of Colombian Adults.
To perform an analysis of the Fourth Colombian Oral Health Study in order to describe the prevalence and extent of gingiva. A national representative sample including 9255 adult individuals was randomly selected using probabilistic methods. Periodontal assessments were performed for all teeth, six sites per tooth. Clinical data collected were: number of teeth, pocket depth and position of the gingival margin. Presence of gingival recession was registered. Demographic, environmental and dental variables were collected. Prevalence and extent of gingival recession at different cut-off values, by tooth types, and factors associated with buccal recession ≥ 4 mm were described. Gingival recession was common in the examined population: 69.7% of subjects had ≥ 1 site with recession ≥ 1 mm, and 30.3% had ≥ 1 site with recession greater than or equal to 3 mm. A total of 28.6% of teeth were affected by recession greater than or equal to 1 mm, and 7.6% by recession ≥ 3 mm. The most frequently affected tooth types were first maxillary molars, first and second mandibular premolars, and the first maxillary premolar. Factors significantly associated with recession greater than or equal to 4 mm were: older age, male gender, lower income, former smoker, diabetes, and less frequent toothbrushing. Gingival recession is a common finding in the Colombian population. Factors associated with recession presence were the same as for periodontitis. Less frequent toothbrushing was associated with deep buccal recession.


PROSPECTS OF C60 FULLERENE APPLICATION AS A MEAN OF PREVENTION AND CORRECTION OF ISCHEMIC-REPERFUSION INJURY IN THE SKELETAL MUSCLE TISSUE.
lack of accurate diagnostic tests for the rapid detection of ischemic injury remains an urgent problem. In this context, a search for specific markers of ischemia as well as new therapeutic agents for prevention and treatment of ischemic injury continues. Water-soluble nano-sized C60 fullerenes, as powerful antioxidants, can act as promising means for correction of various muscle system states, in the base of which lie the destructive effects of free radicals.


Evaluation of the Chagas Western Blot IgG Assay for the Diagnosis of Chagas Disease.
Chagas disease is a debilitating and often fatal pathology resulting from infection by the protozoan parasite Trypanosoma cruzi. In its recommendations, the World Health Organization states that the diagnosis of T. cruzi infection is usually based on the detection of antibodies against T. cruzi antigens and performed with two methodologically different assays. An inconclusive result can be resolved with a third "confirmatory" assay. The objective of this article is to evaluate the effectiveness of the Chagas Western Blot IgG assay (LDBio Diagnostics, Lyon, France) as a confirmatory serologic test. The Chagas Western Blot IgG assay was performed with native antigens derived from a T. cruzi strain of the TcVI genotype. Retrospective sera were provided by two parasitology laboratories (France and Argentina). The sensitivity, specificity, positive predictive value and negative predictive value of the Chagas blot were all 100% in our sera collection. The Chagas blot is an easy and qualitative method for the diagnosis of Chagas disease, with results in less than 2 h. This immunoblot has potential as a supplemental test for the confirmation of the presence of antibodies against T. cruzi in serum specimens. Nonetheless, the very good initial results presented here will need to be confirmed in larger studies.


Resolving sex and gender bias in COVID-19 vaccines R&D and beyond.
The influence of sex and gender in immune response and vaccine outcomes is established in many disease areas, including in COVID-19. Yet, there are notable gaps in the consideration of sex and gender in the analysis and reporting of COVID-19 vaccines clinical trial data. The push for stronger sex and gender integration in vaccines science should be championed by all researchers and stakeholders across the R&D and access ecosystem - not just gender experts. This requires joint action on the tactical framing of customized value propositions (based on stakeholder motivations), the stronger enforcement of existing regulation, tools, and commitments, and aligning the overall agenda to parallel calls on intersectionality, equity diversity and inclusion.


Effect of high blood pressure stress on vascular adrenergic responsiveness in the spontaneously hypertensive rat.
A model in which partial ligation of the left external iliac artery results in a decrease in mean arterial blood pressure to the ipsilateral femoral artery (70 mmHg; protected) while mean pressure increases in the contralateral femoral artery (125 mmHg; unprotected) was used to determine the effect of high blood pressure stress on vascular adrenergic responsiveness. Age-matched (5 week old) male Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were used in the study. Partial ligation was performed at 6 weeks of age and vascular reactivity studies undertaken at 10 weeks of age when the SHR were considered hypertensive (indirect systolic blood pressure greater than 150 mmHg). Force-tension analysis of femoral arterial rings revealed that all tissues contracted maximally at 1.0 gram of preload force. This value was used in subsequent studies on adrenergic responsiveness. Isoproterenol-induced relaxation was significantly attenuated in rings of vascular smooth muscle from unprotected femoral arteries of the SHR, however, the response of rings from protected arteries of the SHR was similar to that of the protected and unprotected arteries of the WKY animal. Unprotected arteries of the SHR exhibited a greater response to norepinephrine stimulation when compared to protected arteries of the SHR as well as unprotected and protected arteries of the WKY animal. This study suggests that alterations in vascular alpha- and beta-adrenergic responsiveness in the SHR are most probably due to the increase in blood pressure.


Pseudomonas aeruginosa AlgR represses the Rhl quorum-sensing system in a biofilm-specific manner.
AlgR controls numerous virulence factors in Pseudomonas aeruginosa, including alginate, hydrogen cyanide production, and type IV pilus-mediated twitching motility. In this study, the role of AlgR in biofilms was examined in continuous-flow and static biofilm assays. Strain PSL317 (DeltaalgR) produced one-third the biofilm biomass of wild-type strain PAO1. Complementation with algR, but not fimTU-pilVWXY1Y2E, restored PSL317 to the wild-type biofilm phenotype. Comparisons of the transcriptional profiles of biofilm-grown PAO1 and PSL317 revealed that a number of quorum-sensing genes were upregulated in the algR deletion strain. Measurement of rhlA::lacZ and rhlI::lacZ promoter fusions confirmed the transcriptional profiling data when PSL317 was grown as a biofilm, but not planktonically. Increased amounts of rhamnolipids and N-butyryl homoserine lactone were detected in the biofilm effluent but not the planktonic supernatants of the algR mutant. Additionally, AlgR specifically bound to the rhlA and rhlI promoters in mobility shift assays. Moreover, PAO1 containing a chromosomal mutated AlgR binding site in its rhlI promoter formed biofilms and produced increased amounts of rhamnolipids similarly to the algR deletion strain. These observations indicate that AlgR specifically represses the Rhl quorum-sensing system during biofilm growth and that such repression is necessary for normal biofilm development. These data also suggest that AlgR may control transcription in a contact-dependent or biofilm-specific manner.


Human papilloma virus genotypes in women from Nayarit, Mexico, with squamous intraepithelial lesions and cervical cancer.
In Mexico cervical cancer (CC) is the most common cause of death from neoplasia in women. Study aimed to analyze the current distribution of Human papillomavirus (HPV) types in women from Nayarit, Mexico, with Squamous intraepithelial lesions (SIL) and Cervical cancer (CC). Between January 2011 and July 2013, cervical samples were collected from female residents of the Mexican state of Nayarit and were analyzed by means of a LINEAR ARRAY® HPV genotyping test. Data analyses were performed using Stata ver. 8.0 statistical software. Of the samples analyzed, 91.2%, HPV DNA was detected. Of these positive samples, 82% were High-risk (HR) viral types. The most prevalent HPV genotypes identified were 16, 58, 31, 18, and 70. Forty two percent of participants had a single infection, while 23 and 26% of participants were infected with two or more HPV genotypes, respectively. HPV 16 was the most prevalent genotype identified and was frequently present as a co-infection with HPV types 18, 51, 52, 59, 66, or 70. Women <20 years of age were most often infected with HPV, and the HPV Quadrivalent vaccine (types 16, 18, 6, and 11), currently available in Mexico, no confers protection against a subset of the HPV genotypes identified in the present study (58, 31, 70, and 35). Thus, it is important evaluate the geographical distribution of specific HPV genotypes in all health of center across Mexico in order to implement a successful vaccination program and to diagnose CC in its early stages.


H-Wave® Device Stimulation: A Critical Review.
Pain treatments have historically centered on drugs, but an "opioid crisis" has necessitated new standards of care, with a paradigm shift towards multi-modal pain management emphasizing early movement, non-narcotics, and various adjunctive therapies. Electrotherapies remain understudied and most lack high-quality clinical trials, despite a desperate need for effective adjunctive options. A systematic search of human clinical studies on H-Wave® device stimulation (HWDS) was conducted as well as a comprehensive review of articles articulating possible HWDS mechanisms of action. Studies unrelated to H-Wave were excluded. Data synthesis summarizes outcomes and study designs, categorized as pre-clinical or clinical. Pre-clinical studies demonstrated that HWDS utilizes a biphasic waveform to induce non-fatiguing muscle contractions which positively affect nerve function, blood and lymph flow. Multiple clinical studies have reported significant benefits for diabetic and non-specific neuropathic pain, where function also improved, and pain medication usage substantially dropped. In conclusion, low- to moderate-quality HWDS studies have reported reduced pain, restored functionality, and lower medication use in a variety of disorders, although higher-quality research is needed to verify condition-specific applicability. HWDS has enough reasonable evidence to be considered as an adjunctive component of non-opioid multi-modal pain management, given its excellent safety profile and relative low cost. Level of Evidence: III.


Identification of fatty acids by electrospray mass spectrometry and tandem mass spectrometry.
Low-energy negative-ion electrospray mass spectrometry (ESI-MS) and ESI-MS/MS were used to characterize saturated and unsaturated fatty acids. The carbon number and degree of unsaturation of fatty acids were determined using ESI-MS, and MS/MS was used to localize some double bond positions of mono-and polyunsaturated fatty acids. For compounds with up to two unsaturated bonds, fragmentation was dominated by loss of H2O from the carboxyl moiety and very low-intensity peaks generated from bonds cleaved at carbons alpha and/or beta to sites of unsaturation. Fragmentation of monounsaturated fatty acids was minimal using this soft method of mass spectrometric analysis, but increased with progressively greater degrees of fatty acid unsaturation. There was extensive hydride migration during ESI-MS/MS of compounds with three or more double bonds. Although this behavior complicated localization of double and triple bonds, the spectra were reproducible. Many peaks could not be definitively assigned to specific product ions, but the spectra of standards and complementary natural products were similar and isobaric compounds could be differentiated. The utility of this technique to examine biological samples was shown by analysis of the fatty acid composition of cod liver oil. Detection limits for negative-ion ESI-MS/MS were at or below 1 pg.


How far?: Using geographical information systems (GIS) to examine maternity care access for expectant mothers in a rural state.
Various factors have made rural access to maternity care a significant problem for rural women. The geographic distance between a mother's county of residence and the county in which she gave birth was examined in a rural state. Analyzing North Dakota county-level data using geographic information system (GIS) software, women from over half of the state's counties, making up nearly 18% of all births, were found to be over 40 miles to the hospital in which they gave birth. These findings suggest that rural women may experience significant geographic barriers as they receive health services in the prenatal, delivery, and postpartum periods of their pregnancy. We highlight the value of GIS, particularly geovisualization power, and note models of care that may be effective for rural women.


Augmentation and replacement cystoplasty: sonographic findings.
Sonographic evaluation of the urinary tract after bladder augmentation and replacement procedures often reveals unexpected findings that result from incorporation of bowel into the urinary bladder wall. Familiarity with such findings is important to avoid misinterpreting them as abnormalities. The authors reviewed the sonograms of 47 patients. The most common findings were thick or irregularly shaped bladder walls (96%), pseudomasses within the bladder lumen (89%), and fine debris or linear strands (47%). Pseudomasses were potentially the most confusing; they are usually attributable to normal bowel folds, intraluminal mucus collections, or segments of bowel that have been intussuscepted into the bladder to prevent reflux.


[Diagnostic difficulties in recognizing partial intestinal occlusion].
The authors present a cases of intestinal occlusion ileus, which lasted more than 10 months. Diagnostic difficulties were caused by atypical course of a diseases. Authors emphasize the role of follow-up barium study in the process of reaching the diagnosis in patients with the suspicion of the ileus.


Duration and outcome of persistent candidaemia in newborn infants.
The aims of the study were to define the duration of candidaemia in newborn infants and to determine the incidence of persistent hospital-acquired candidaemia and its associated morbidity and mortality compared with non-persistent candidaemia. This retrospective study, included 56 neonates admitted to the neonatal intensive care unit from 1996 to 2000 who had one or more positive blood cultures for Candida spp. The most prevalent pathogen was Candida albicans (64.3%). Mean disease duration was 6.9 +/- 5.5 days (median 6 days). Twenty-nine patients (52%) had a positive blood culture for >5 days (persistent candidaemia). There were no statistically significant differences between the infants with persistent and non-persistent candidaemia in background or predisposing clinical factors. Fungal endocarditis was present in four patients (13.7%) with persistent disease and one patient (3.7%) with non-persistent disease (odds ratio 4.19), and uveitis developed in one patient. Ten patients (17.8%) died--five with persistent and five with non-persistent disease (P = 1.0). These findings indicate that persistent neonatal candidaemia may be associated with an increased risk of Candida endocarditis, but not with other complications or increased mortality.


Outcomes of revision total hip replacement for infection after grading according to a standard protocol.
Periprosthetic infection following total hip replacement can be a catastrophic complication for the patient. The treatments available include single-stage exchange, and two-stage exchange. We present a series of 50 consecutive patients with a diagnosis of infected total hip replacement who were assessed according to a standardised protocol. Of these, 11 underwent single-stage revision arthroplasty with no recurrence of infection at a mean of 6.8 years follow-up (5.5 to 8.8). The remaining 39 underwent two-stage revision, with two recurrences of infection successfully treated by a second two-stage procedure. At five years, significant differences were found in the mean Harris Hip Scores (single-stage 87.8; two-stage 75.5; p = 0.0003) and in a visual analogue score for satisfaction (8.6; 6.9; p = 0.001) between the single- and two-stage groups. Single-stage exchange is successful in eradicating periprosthetic infection and results in excellent functional and satisfaction scores. Identification of patients suitable for the single-stage procedure allows individualisation of care and provides as many as possible with the correct strategy in successfully tackling their periprosthetic infection.


Long-term potentiation and spatial learning are associated with increased phosphorylation of TrkB and extracellular signal-regulated kinase (ERK) in the dentate gyrus: evidence for a role for brain-derived neurotrophic factor.
In this study, the authors investigate changes in the presynaptic terminal of the dentate gyrus that accompany 2 types of hippocampal-dependent plasticity: spatial learning and long-term potentiation (LTP). Parallel changes occurred in the dentate gyrus of rats that had undergone training in the Morris water maze and had sustained LTP. In both cases, KCl-induced brain-derived neurotrophic factor release was increased, and this was accompanied by increased phosphorylation of TrkB and the mitogen-activated protein kinase, ERK. Glutamate release was also enhanced, and the data suggest that this may be a consequence of increased activation of TrkB and ERK. Because the data indicate that similar cellular modifications are shared by these 2 forms of plasticity, they provide circumstantial evidence that LTP satisfies some of the requirements of a memory-inducing cellular substrate.


Anti-inflammatory and anti-nociceptive activity of the water decoction Desmodium gangeticum.
The water decoction of root and aerial parts of Desmodium gangeticum (Leguminosae) was examined for anti-inflammatory and anti-nociceptive activity in experimental animals. The root and aerial decoction in doses of 5, 10 and 20 mg /kg caused a dose-dependent inhibition of swelling caused by carrageenin equivalent to 14.58-51.02% protection and 14.43-38.67%, respectively, in cotton pellet granuloma. There was a significant increase in analgesio-meter-induced force equivalent to 6.56-67.66% protection and 22.18-73.83% protection in acetic acid-induced writhing. The result establishes the traditional use of water decoction of Desmodium gangeticum codified in Indian System of Medicine.


The thioredoxin system in aging muscle: key role of mitochondrial thioredoxin reductase in the protective effects of caloric restriction?
Cellular redox balance is maintained by various antioxidative systems. Among those is the thioredoxin system, consisting of thioredoxin, thioredoxin reductase, and NADPH. In the present study, we examined the effects of caloric restriction (2 mo) on the expression of the cytosolic and mitochondrial thioredoxin system in skeletal muscle and heart of senescent and young rats. Mitochondrial thioredoxin reductase (TrxR2) is significantly reduced in aging skeletal and cardiac muscle and renormalized after caloric restriction, while the cytosolic isoform remains unchanged. Thioredoxins (mitochondrial Trx2, cytosolic Trx1) are not influenced by caloric restriction. In skeletal and cardiac muscle of young rats, caloric restriction has no effect on the expression of thioredoxins or thioredoxin reductases. Enforced reduction of TrxR2 (small interfering RNA) in myoblasts under exposure to ceramide or TNF-alpha causes a dramatic enhancement of nucleosomal DNA cleavage, caspase 9 activation, and mitochondrial reactive oxygen species release, together with reduced cell viability, while this TrxR2 reduction is without effect in unstimulated myoblasts under basal conditions. Oxidative stress in vitro (H2O2 in C2C12 myoblasts and myotubes) results in different changes: TrxR2, Trx2, and Trx1 are induced without alterations in the cytosolic thioredoxin reductase isoforms. Thus aging is associated with a TrxR2 reduction in skeletal muscle and heart, which enhances susceptibility to apoptotic stimuli but is renormalized after short-term caloric restriction. Exogenous oxidative stress does not result in these age-related changes of TrxR2.


Genome-based identification of beet curly top Iran virus infecting sugar beet in Turkey and investigation of its pathogenicity by agroinfection.
Beet curly top disease (BCTD) is a yield-limiting viral infection of sugar beet (Beta vulgaris) throughout the arid and semi-arid regions of the world. Two virus species, belonging to two different genera of the family Geminiviridae (Curtovirus and Becurtovirus) had been described as the disease's causative agents on sugar beet. Despite the detection of the BCTD in some sugar beet fields of Turkey sixty years ago, the genome based characterization of BCTD-associated viruses have not been studied previously. In this study, 628 sugar beet plants exhibiting BCTD symptoms were collected from fourteen cities in central Anatolia, the major sugar beet production areas in Turkey. PCR assays of these samples using the respective Curtovirus and Becurtovirus genus-specific primers indicated that the Turkish sugar beet samples' viral sequences belong only to the genus Becurtovirus. The results of sequencing and phylogenetic analysis of the partial genome of the virus obtained from fourteen cities confirmed that BCTD-associated virus in Turkish sugar beet fields is beet curly top Iran virus (BCTIV-Becurtovirus) species. The whole genome of the collected viruses from fourteen cities were amplified by the rolling circle amplification (RCA) and the five most phylogenetically diverse viruses obtained from Afyon, Ankara, Adapazarı, Yozgat and Aksaray were sequenced. The results of whole genome sequence analysis indicated >98 % sequence identities with that of a BCTIV variants reported from Urmia province (bordering Turkey) of Iran. A virus genome from Yozgat city had a genomic sequence identity of >97 % with those of BCTIV isolated from cowpea, tomato, pepper and sugar beet in the northern part of Iran. These results suggested that the spread of BCTIV through the region could create a significant threat to the production of sugar beet as well as other agricultural crops. A tandem dimer of a BCTIV-Turkish variant isolated from Ankara city was cloned into Agrobacterium plasmid to be used for agro-infection studies. Agroinoculation of this construct on sugar beet leaves generated severe BCTD symptoms (84 %) which were also confirmed by RCA and qPCR analysis. These results constituted the first genome based characterization of BCTIV Turkish variants and the first report of BCTIV spreading out of Iran.


Radiofrequency Ablation Covering the Entire Tumor Blood Drainage Area Improves Survival in Hepatocellular Carcinoma.
Hepatocellular carcinoma has been considered to disseminate through the tumor blood drainage area. To improve curation rates, treatment should cover this area as it may contain satellite lesions. This retrospective study aimed to investigate whether radiofrequency ablation (RFA) completely covering the blood drainage area can improve the overall and disease-free survival. We enrolled 526 patients who underwent computed tomography during hepatic arteriography following RFA from April 2001 to May 2019. Patients were categorized into a covered group in which the blood drainage area was completely covered by RFA and a noncovered group in which coverage was incomplete. The primary endpoint was the overall survival rate; secondary outcomes included disease-free survival rate, distant intrahepatic and local recurrence rate, and changes in the Child-Pugh score. There were no significant differences in baseline characteristics between the two groups. Cumulative overall survival rates were significantly higher in the covered group than in the noncovered group (hazard ratio, 0.63; 95% confidence interval, 0.48-0.84; P = 0.002). On multivariate Cox proportional hazard model analysis, age <65 years, Child-Pugh class A, and coverage of the entire drainage area were independent protective factors. Child-Pugh worsened in 11 (4.2%) patients in the covered group compared to 18 (6.7%) patients in the noncovered group. Conclusion: RFA covering the complete drainage area improved overall survival without decreasing liver function.


Prolific authorship in orthodontic scientific publishing.
To identify the 10 most numerically prolific authors publishing in the field of orthodontics for each year over the last decade (2011-2020), describe the characteristics of these outputs and identify trends in the types of study being published. A Scopus literature search was conducted to identify the 10 most numerically prolific publishing authors in orthodontics for each year during this decade. Number and characteristics of all publications for each author were analysed with descriptive and inferential statistics. Forty-nine different individual authors were identified who were collectively prolific for between 1-8 years within the assessment decade. These authors published a total of 2025 papers, with a median annual output of 18 papers per year; however, half of these authors published between 15-24 papers per year (range 5-200). Amongst authors, 2 or more collaborated on only 7% of the identified papers. The median number of authors per paper was 5 (range 1-27) with significant variation according to study design (P < .001). The majority of authors originated from Brazil (19.3%), Italy (14.1%) and India (12.7%). Most papers described non-prospective clinical studies (38.1%), case reports or case series (11.1%) and narrative reviews (10.8%). Finally, prolific authors had a smaller annual output when publishing in orthodontic journals (P < .001) and when publishing experimental primary research (P = .04). A cohort of prolific authors in orthodontics between 2011-2020 was identified. Extreme variation was found in annual output between these authors but case reports, non-prospective clinical studies and narrative reviews predominated.


Superhydrophobicity in perfection: the outstanding properties of the lotus leaf.
Lotus leaves have become an icon for superhydrophobicity and self-cleaning surfaces, and have led to the concept of the 'Lotus effect'. Although many other plants have superhydrophobic surfaces with almost similar contact angles, the lotus shows better stability and perfection of its water repellency. Here, we compare the relevant properties such as the micro- and nano-structure, the chemical composition of the waxes and the mechanical properties of lotus with its competitors. It soon becomes obvious that the upper epidermis of the lotus leaf has developed some unrivaled optimizations. The extraordinary shape and the density of the papillae are the basis for the extremely reduced contact area between surface and water drops. The exceptional dense layer of very small epicuticular wax tubules is a result of their unique chemical composition. The mechanical robustness of the papillae and the wax tubules reduce damage and are the basis for the perfection and durability of the water repellency. A reason for the optimization, particularly of the upper side of the lotus leaf, can be deduced from the fact that the stomata are located in the upper epidermis. Here, the impact of rain and contamination is higher than on the lower epidermis. The lotus plant has successfully developed an excellent protection for this delicate epistomatic surface of its leaves.


Effect of Strength Training Protocol on Bone Mineral Density for Postmenopausal Women with Osteopenia/Osteoporosis Assessed by Dual-Energy X-ray Absorptiometry (DEXA).
This study aims to introduce a resistance training protocol (6 repetitions × 70% of 1 maximum repetition (1RM), followed by 6 repetitions × 50% of 1RM within the same set) specifically designed for postmenopausal women with osteopenia/osteoporosis and monitor the effect of the protocol on bone mineral density (BMD) in the lumbar spine, assessed by dual-energy X-ray absorptiometry (DEXA). The subjects included in the study were 29 postmenopausal women (56.5 ± 2.8 years) with osteopenia or osteoporosis; they were separated into two groups: the experimental group (n = 15), in which the subjects participated in the strength training protocol for a period of 6 months; and the control group (n = 14), in which the subjects did not take part in any physical activity. BMD in the lumbar spine was measured by DEXA. The measurements were performed at the beginning and end of the study. A statistically significant increase (Δ% = 1.82%) in BMD was observed at the end of the study for the exercise group (0.778 ± 0.042 at baseline vs. 0.792 ± 0.046 after 6 months, p = 0.018, 95% CI [-0.025, -0.003]); while an increase was observed for the control group (Δ% = 0.14%), the difference was not statistically significant (0.762 ± 0.057 at baseline vs. 0.763 ± 0.059, p = 0.85, 95% CI [-0.013, 0.011]). In conclusion, our strength training protocol seems to be effective in increasing BMD among women with osteopenia/osteoporosis and represents an affordable strategy for preventing future bone loss.


Strategies for Improving Ocular Drug Bioavailability and Corneal Wound Healing with Chitosan-Based Delivery Systems.
The main inconvenience of conventional eye drops is the rapid washout of the drugs due to nasolacrimal drainage or ophthalmic barriers. The ocular drug bioavailability can be improved by either prolonging retention time in the cul-de-sac or by increasing the ocular permeability. The focus of this review is to highlight some chitosan-based drug delivery approaches that proved to have good clinical efficacy and high potential for use in ophthalmology. They are exemplified by recent studies exploring in-depth the techniques and mechanisms in order to improve ocular bioavailability of the active substances. Used alone or in combination with other compounds with synergistic action, chitosan enables ocular retention time and corneal permeability. Associated with other stimuli-responsive polymers, it enhances the mechanical strength of the gels. Chitosan and its derivatives increase drug permeability through the cornea by temporarily opening tight junctions between epithelial cells. Different types of chitosan-based colloidal systems have the potential to overcome the ocular barriers without disturbing the vision process. Chitosan also plays a key role in improving corneal wound healing by stimulating the migration of keratinocytes when it is used alone or in combination with other compounds with synergistic action.


Accelerated approval of oncology products: a decade of experience.
We review the regulatory history of the accelerated approval process and summarize the U.S. Food and Drug Administration experience with accelerated approvals in oncology. The accelerated approval regulations, promulgated in 1992, allow approval of drugs for serious or life-threatening diseases on the basis of a surrogate endpoint that is reasonably likely to predict clinical benefit, such as survival or symptom benefit, pending completion of studies designed to confirm clinical benefit, referred to as phase 4 commitments, which are required to be conducted with due diligence. From 1992 to 2004, 22 applications involving anticancer drugs or biologics were approved. Of these 22 applications, accelerated approval was granted to 15 on the basis of findings from studies without an active comparator (i.e., single-arm studies or studies comparing two dose levels) and to the remaining seven on the basis of one or more randomized studies. Of the 22 approved applications, six (i.e., applications for dexrazoxane, irinotecan, capecitabine, docetaxel, imatinib mesylate, and oxaliplatin) have had one or more indications converted to regular approval. This review reports information that was presented at an Oncologic Drugs Advisory Committee meeting held in March 2003; it also presents a discussion of accelerated approval study designs, the study populations evaluated in the accelerated approval and confirmatory settings, and the integration of accelerated approval into a comprehensive drug development plan.


Self-organization of modular network architecture by activity-dependent neuronal migration and outgrowth.
The spatial distribution of neurons and activity-dependent neurite outgrowth shape long-range interaction, recurrent local connectivity and the modularity in neuronal networks. We investigated how this mesoscale architecture develops by interaction of neurite outgrowth, cell migration and activity in cultured networks of rat cortical neurons and show that simple rules can explain variations of network modularity. In contrast to theoretical studies on activity-dependent outgrowth but consistent with predictions for modular networks, spontaneous activity and the rate of synchronized bursts increased with clustering, whereas peak firing rates in bursts increased in highly interconnected homogeneous networks. As Ca2+ influx increased exponentially with increasing network recruitment during bursts, its modulation was highly correlated to peak firing rates. During network maturation, long-term estimates of Ca2+ influx showed convergence, even for highly different mesoscale architectures, neurite extent, connectivity, modularity and average activity levels, indicating homeostatic regulation towards a common set-point of Ca2+ influx.


Metabolic reprogramming of T regulatory cells in the hypoxic tumor microenvironment.
Metabolic dysregulation in the hypoxic tumor microenvironment (TME) is considered as a hallmark of solid tumors, leading to changes in biosynthetic pathways favoring onset, survival and proliferation of malignant cells. Within the TME, hypoxic milieu favors metabolic reprogramming of tumor cells, which subsequently affects biological properties of tumor-infiltrating immune cells. T regulatory cells (Tregs), including both circulating and tissue-resident cells, are particularly susceptible to hypoxic metabolic signaling that can reprogram their biological and physicochemical properties. Furthermore, metabolic reprogramming modifies Tregs to utilize alternative substrates and undergo a plethora of metabolic events to meet their energy demands. Major impact of this metabolic reprogramming can result in differentiation, survival, excessive secretion of immunosuppressive cytokines and proliferation of Tregs within the TME, which in turn dampen anti-tumor immune responses. Studies on fine-tuning of Treg metabolism are challenging due to heterogenicity of tissue-resident Tregs and their dynamic functions. In this review, we highlight tumor intrinsic and extrinsic factors, which can influence Treg metabolism in the hypoxic TME. Moreover, we focus on metabolic reprogramming of Tregs that could unveil potential regulatory networks favoring tumorigenesis/progression, and provide novel insights, including inhibitors against acetyl-coA carboxylase 1 and transforming growth factor beta into targeting Treg metabolism for therapeutic benefits.


Outcomes results from the evaluation of the APA/HRSA Faculty Scholars Program.
The goal of the Ambulatory Pediatric Association/Health Resources and Services Administration National Faculty Development Scholars Program was to improve primary care education in the pediatric setting. The program evaluation focused on four stake-holder objectives: 1) increase the educational skills of community and generalist faculty; 2) create pediatric leadership focused on changing the culture within the medical community to support primary care education; 3) develop an infrastructure that supports sustained faculty development efforts at the local, regional, and national level; and 4) include content areas consistent with Health Resources and Services Administration contract requirements. A multimethod evaluation plan, focused on the 107 completing scholars, was implemented utilizing six evaluation instruments. Key outcomes from both quantitative and qualitative outcome measures reveal that all evaluation objectives were achieved. Scholars presented 438 local workshops and 161 regional/national workshops focused on pediatric education with a combined attendance of 7939 participants. More than half of the scholars have now assumed a leadership position in education associated with program participation. Ninety-three percent of the scholars reported organizational/infrastructure changes associated with their program participation ranging from increased numbers of community teaching sites to specific resource allocations to support of faculty development. The outcomes of this evaluation reveal that the faculty development program achieved its objectives, with participants leading workshops, impacting faculty development infrastructure, advancing their own careers, and being strategically positioned in leadership roles with the skills to improve primary care education in the ambulatory setting.


The Pesticide Metabolites Paraoxon and Malaoxon Induce Cellular Death by Different Mechanisms in Cultured Human Pulmonary Cells.
Organophosphorus (OP) pesticides are known to induce pulmonary toxicity in both humans and experimental animals. To elucidate the mechanism of OP-induced cytotoxicity, we examined the effects of parathion and malathion and their respective metabolites, paraoxon and malaoxon, on primary cultured human large and small airway cells. Exposure to paraoxon and malaoxon produced a dose-dependent increase in cytotoxicity following a 24-hour exposure, while treatment with parathion or malathion produced no effects at clinically relevant concentrations. Exposure to paraoxon-induced caspase activation, but malaoxon failed to induce this response. Since caspases have a major role in the regulation of apoptosis and cell death, we evaluated OP-induced cell death in the presence of a caspase inhibitor. Pharmacological caspase inhibition protected against paraoxon-induced cell death but not malaoxon-induced cell death. These data suggest that caspase activation is a key signaling element in paraoxon-induced cell death, but not malaoxon-induced cellular death in the pulmonary epithelium.


Neotropical mustelids: fecal metabolome diversity and its potential for taxonomic discrimination.
Chemical profiles of non-invasive biological material, such as feces, have great potential to study elusive animals or those with low population densities. Here, we use a metabolomic approach to evaluate Neotropical mustelids as a biological model to describe the diversity of the metabolites present in fecal samples, as well as to evaluate the potential of chemical profiles for taxonomic discrimination. We collected fecal samples from captive individuals of 5 species of mustelids occurring in Brazil and analyzed them by liquid chromatography coupled to high-resolution mass spectrometry. Over 200 compounds have been annotated; "bile acids, alcohols and derivatives" was the most expressive class in the metabolome of all the species. We successfully discriminated 3 taxonomic groups: 1-tayra (Eira barbara); 2-otters (Lontra longicaudis and Pteronura brasiliensis; 1); and 3-grisons (Galictis vittata and Galictis cuja). Several compounds seemed to be associated with food intake and the digestive process, while others were found for the first time in Neotropical mustelids. We concluded that mustelids show high metabolome diversity and that species-specific identification through metabolomic profiles is possible, thus contributing to the development and implementation of additional non-invasive approaches in the study of mustelids.


Anti-TNF immunotherapy reduces CD8+ T cell-mediated antimicrobial activity against Mycobacterium tuberculosis in humans.
The incidence of tuberculosis is increased during treatment of autoimmune diseases with anti-TNF antibodies. This is a significant clinical complication, but also provides a unique model to study immune mechanisms in human tuberculosis. Given the key role for cell-mediated immunity in host defense against Mycobacterium tuberculosis, we hypothesized that anti-TNF treatment impairs T cell-directed antimicrobial activity. Anti-TNF therapy reduced the expression in lymphocytes of perforin and granulysin, 2 components of the T cell-mediated antimicrobial response to intracellular pathogens. Specifically, M. tuberculosis-reactive CD8+CCR7-CD45RA+ effector memory T cells (TEMRA cells) expressed the highest levels of granulysin, lysed M. tuberculosis, and infected macrophages and mediated an antimicrobial activity against intracellular M. tuberculosis. Furthermore, TEMRA cells expressed cell surface TNF and bound the anti-TNF therapeutic infliximab in vitro, making them susceptible to complement-mediated lysis. Immune therapy with anti-TNF was associated with reduced numbers of CD8+ TEMRA cells and decreased antimicrobial activity against M. tuberculosis, which could be rescued by the addition of CD8+ TEMRA cells. These results suggest that anti-TNF therapy triggers a reduction of CD8+ TEMRA cells with antimicrobial activity against M. tuberculosis, providing insight into the mechanism whereby key effector T cell subsets contribute to host defense against tuberculosis.


Application of mussels as biosamplers for characterization of faecal pollution in coastal recreational waters.
Sources of faecal pollution in coastal recreational waters may be identified by analysing different host associated microorganisms or molecular markers. However, the microbial targets are often present at low numbers in moderately impacted waters, and often exhibit significant temporal and spatial variability in waters with fluctuating faecal loads. This patchy occurrence can limit successful detection of relevant targets in microbial source tracking studies. In this study, we explored the possibility for using the blue mussel (Mytilus edulis) as a biosampler for accumulation of faecal bacteria relevant for microbial source tracking. Non-contaminated blue mussels were transferred to three coastal recreational waters affected by faecal pollution of unknown origin. Molecular markers associated with animal and human waste were targeted by PCR and compared in seawater and mussel samples. The results demonstrated that transplanted mussels in simple enclosures accumulated and retained elevated levels of molecular markers associated with different types of faecal pollution. The targets included a novel putative human associated E. coli subgroup B2 VIII clone, and animal and human associated markers in enterococci (esp, M19, M66, M90, and M91). Human (sewage) associated markers including esp and M66 were sometimes not detectable in seawater samples despite known wastewater contamination, whereas the markers were detectable in mussels. We suggest that transplanted mussels should be considered as potential biosamplers in studies focusing on identifying source of faecal pollution in low or moderately impacted recreational waters. Bioaccumulation of molecular markers in mussels for several days may represent the water quality better than traditional grab samples from the water column.


[Drug-induced syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Review of literature].
The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is caused by an incapacity of plasmatic hypotonia to inhibit antidiuretic hormone (ADH) secretion. This phenomenon leads to a water retention and an expanded extracellular fluid volume, and secondary to a dilution of plasmatic sodium and also to a renal loss of sodium. The SIADH is a relatively rare syndrome, which may occur in various circumstances: central nervous system diseases, cancers, infections... Sometimes, it may be observed as a drug-related side effect: carbamazepine, chlorpropamide, antidepressors, anticancer drugs are particularly involved.


Adsorption and activation of CO over flat and stepped Co surfaces: a first principles analysis.
The adsorption and activation of CO over flat Co{0001}, corrugated Co{1120}, and stepped Co{1012} and Co{1124} surfaces have been analyzed using periodic density functional theory calculations. CO strongly chemisorbs on all these surfaces but does not show a strong dependence on the surface structure. The calculated structure of adsorbed CO on Co{0001} at 1/3 monolayer (ML) of coverage was found to be in good agreement with the experiment. The barrier for CO dissociation over Co{0001} was found to decrease with decreasing CO coverage, taking on a value of 232 kJ/mol at 1/4 ML and 218 kJ/mol at 1/9 ML. The presence of the "zigzag" channel on Co{1120} enhances the reactivity slightly by reducing the barrier for CO dissociation to 195 kJ/mol. In contrast, the stepped Co{1012} and Co{1124} surfaces are much more active than the flat and corrugated surfaces. Both stepped surfaces provide direct channels for CO dissociation that do not have barriers with respect to gas-phase CO. In general the activation barriers lower as the reaction energies become more exothermic. Reconstruction of the step edges that occur in the product state, however, prevents a linear correlation between the reaction energy and the activation energy.


Diet and risk of breast cancer.
Diet may play a role in both promoting and inhibiting human breast cancer development. In this review, nutritional risk factors such as consumption of dietary fat, meat, fiber, and alcohol, and intake of phytoestrogen, vitamin D, iron, and folate associated with breast cancer are reviewed. These nutritional factors have a variety of associations with breast cancer risk. Type of fat consumed has different effects on risk of breast cancer: consumption of meat is associated with heterocyclic amine (HCA) exposure; different types of plant fiber have various effects on breast cancer risk; alcohol consumption may increase the risk of breast cancer by producing acetaldehyde and reactive oxygen species (ROS); intake of phytoestrogen may reduce risk of breast cancer through genomic and non-genomic action; vitamin D can reduce the risk of breast cancer by inhibiting the process of cancer invasion and metastasis; intake of dietary iron may lead to oxidative stress, DNA damage, and lipid peroxidation; and lower intake of folate may be linked to a higher risk of breast cancer.


Food and Nutrition Related Concerns Post Lockdown during COVID-19 Pandemic and Their Association with Dietary Behaviors.
This study aimed to explore food and nutrition related concerns during the post-lockdown period and their impacts on food shopping, preparation, and eating behaviors. A cross-sectional study was conducted through online questionnaire. We collected data on food and nutrition related concerns, socio-demographic characteristics, and changes in dietary behaviors. A total of 2267 responses were received from people living in 31 provinces across mainland China and 1994 participants were included in the final analysis. Linear and multinomial logistic regression analyses were performed to evaluate the association among food and nutrition related concerns, socio-demographic factors, and dietary behaviors Results: About 56% of participants reported moderate to high levels of concerns related to food and nutrition. Contracting the virus when dining out or through contaminated foods were the top two concerns, followed by overnutrition. Higher levels of concerns were found among people who were older, overweight, or obese, having lower income and education, and living in urban areas, or whose family contained vulnerable individuals. Compared with the pre-COVID-19 period, people who were more concerned about food and nutrition were more likely to report changes in their food purchases and consumption; they were also more likely to eat from individual plates, using serving chopsticks, and separating plates and utensils for raw and cooked foods during the post COVID-19 lockdown period. Food and nutrition related concerns during the post-lockdown period were prevalent and associated with changes in dietary behaviors. Preventative policies and nutritional guidance should be developed to address these concerns in order to reduce inappropriate dietary behaviors amid public health crises.


Two-in-One Chemogene Assembled from Drug-Integrated Antisense Oligonucleotides To Reverse Chemoresistance.
Combinatorial chemo and gene therapy provides a promising way to cure drug-resistant cancer, since the codelivered functional nucleic acids can regulate drug resistance genes, thus restoring sensitivity of the cells to chemotherapeutics. However, the dramatic chemical and physical differences between chemotherapeutics and nucleic acids greatly hinder the design and construction of an ideal drug delivery system (DDS) to achieve synergistic antitumor effects. Herein, we report a novel approach to synthesize a nanosized DDS using drug-integrated DNA with antisense sequences (termed "chemogene") to treat drug-resistant cancer. As a proof of concept, floxuridine (F), a typical nucleoside analog antitumor drug, was incorporated in the antisense sequence in the place of thymine (T) based on their structural similarity. After conjugation with polycaprolactone, a spherical nucleic acid (SNA)-like two-in-one chemogene can be self-assembled, which possesses the capabilities of rapid cell entry without the need for a transfection agent, efficient downregulation of drug resistance genes, and chronic release of chemotherapeutics for treating the drug-resistant tumors in both subcutaneous and orthotopic liver transplantation mouse models.