Isolated limb perfusion as a treatment option for rare types of tumours.
Isolated limb perfusion (ILP) is an established and effective treatment for advanced melanoma and soft tissue sarcomas of the extremities with a high overall response rate. The aim of this study was to describe our experience of ILP for more rare types of tumours. Patients with Merkel cell carcinoma (MCC) (n = 4), squamous cell carcinoma (SCC) (n = 2), B-cell lymphoma (n = 1), desmoid tumours (n = 3), pigmented villonodular synovitis (PVNS) (n = 1) and giant cell tumour (n = 1) were treated with ILP and analysed retrospectively. The four patients with in-transit MCC had three complete responses (CR) and one partial response (PR); the two patients with SCC had one CR and one stable disease (SD); the patients with desmoid tumours had two PR and one SD. A CR was also observed for the patient with a giant cell tumour, but the patient with PVNS had a SD. The patient with cutaneous metastases of B-cell lymphoma showed a CR, however with rapid systemic progression. Local toxicity according to Wieberdink was grade II in 10 patients (83%) and grade III in two patients (17%). These results show that ILP can be used as a treatment option also for more rare disease entities when other treatments have failed.


Combined PTEN Knockdown and Local Insulin in Chronic Experimental Diabetic Neuropathy.
Diabetic polyneuropathy (DPN) renders progressive sensory neurodegeneration linked to hyperglycemia and its associated metabolopathy. We hypothesized that there may be additive impacts of direct insulin signaling, independent of glycemia and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) knockdown on neuropathy. Our targets for combined interventions were neurons and Schwann cells (SCs) in vitro and chronic type 1 DPN in mice. Insulin receptor expression was not altered by high-glucose conditions in neurons or SCs, and insulin promoted survival of neurons and proliferation of SCs in vitro. There were additive impacts between insulin signaling and PTEN knockdown in sensory neuron outgrowth and in axon myelination by SCs. In a chronic mouse model of experimental DPN, unilateral intra-hind paw injections of a PTEN siRNA and local insulin had additive impacts on correcting key features of chronic experimental DPN independent of glycemia, including motor axon conduction and thermal and mechanical sensory loss. Moreover, combined interventions improved sural and tibial nerve myelin thickness, hind paw epidermal innervation, and pAkt expression in dorsal root ganglion sensory neurons. We conclude that local PTEN inhibition or knockdown and insulin provide additive trophic support for sensory neurons and SCs while reversing key abnormalities of experimental DPN but without requiring metabolic correction. Impaired growth and plasticity of neurons may contribute to chronic diabetic polyneuropathy. Both direct insulin signaling of neurons and neuron knockdown of the protein phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a roadblock to neuronal regenerative growth, offer direct support of neurons. Direct insulin and PTEN knockdown using siRNA had additive impacts on neuron survival, Schwann cell proliferation, neuron outgrowth, and myelination in vitro. Combined local insulin and PTEN siRNA hind paw injections improved abnormalities in chronic experimental diabetic polyneuropathy, including sensory axon loss, independently of glycemia.


Sessile serrated lesions: Clinicopathological characteristics, endoscopic diagnosis, and management.
The 2019 World Health Organization (WHO) Classification of Tumours of the Digestive System (5th edition) introduced the term "sessile serrated lesion" (SSL) to replace the term "sessile serrated adenoma/polyp" (SSA/P). SSLs are early precursor lesions in the serrated neoplasia pathway that result in colorectal carcinomas with BRAF mutations, methylation for DNA repair genes, a CpG island methylator phenotype, and high levels of microsatellite instability. Some of these lesions can rapidly become dysplastic or invasive carcinomas that exhibit high lymphatic invasion and lymph node metastasis potential. The 2019 WHO classification noted that dysplasia arising in an SSL most likely is an advanced polyp, regardless of the morphologic grade of the dysplasia. Detecting SSLs with or without dysplasia is critical; however, detection of SSLs is challenging, and their identification by endoscopists and pathologists is inconsistent. Furthermore, indications for their endoscopic treatment have not been established. Moreover, SSLs are considered to contribute to the development of post-colonoscopy colorectal cancers. Herein, the clinicopathological and endoscopic characteristics of SSLs, including features determined using white light and image-enhanced endoscopy, therapeutic indications, therapeutic methods, and surveillance are reviewed based on the literature. This information may lead to more intensive research to improve detection, diagnosis, and rates of complete resection of these lesions and reduce post-colonoscopy colorectal cancer rates.


Iatrogenic Vascular Injuries of the Abdomen and Pelvis: The Experience at a Hellenic University Hospital.
The aim of this study is to present the experience of a Vascular Division at a Hellenic University hospital concerning the management of iatrogenic vascular injuries (IVIs) of the abdomen or pelvis. This is a retrospective study evaluating all IVIs reported during a 10-year period in our institution. Only injuries warranting a vascular surgeon consultation were included in the study. Non-iatrogenic injuries were not included. Mortality and major complications within 30 days were evaluated. Overall, 70 cases were recorded, with 41% being venous and 59% being arterial injuries. Iliac arteries (51%) were the most common location and rupture/lacerations (73%) were the most common type of injury. General surgery (61.5%) and cardiology (30%) procedures were the most frequently involved procedures. A 30-day mortality was 5.7%, with 30% of cases treated conservatively. Synthetic bypass grafting (odds ratio [OR] = 65.0; 95% confidence interval [CI], 4.022-1050.358; P = .003) and male gender (OR = 83.77; 95% CI, 4.040-1736.738; P = .004) were associated with death. Iatrogenic vascular injuries of the abdomen or pelvis are usually associated with general surgery and endovascular procedures. When vascular consultation is requested early, mortality could remain low. However, a selected number of stable patients with retroperitoneal or pelvic hematomas could be treated conservatively, yielding satisfying results.


Migraine with aura detection and subtype classification using machine learning algorithms and morphometric magnetic resonance imaging data.
Migraine with aura (MwA) is a neurological condition manifested in moderate to severe headaches associated with transient visual and somatosensory symptoms, as well as higher cortical dysfunctions. Considering that about 5% of the world's population suffers from this condition and manifestation could be abundant and characterized by various symptoms, it is of great importance to focus on finding new and advanced techniques for the detection of different phenotypes, which in turn, can allow better diagnosis, classification, and biomarker validation, resulting in tailored treatments of MwA patients. This research aimed to test different machine learning techniques to distinguish healthy people from those suffering from MwA, as well as people with simple MwA and those experiencing complex MwA. Magnetic resonance imaging (MRI) post-processed data (cortical thickness, cortical surface area, cortical volume, cortical mean Gaussian curvature, and cortical folding index) was collected from 78 subjects [46 MwA patients (22 simple MwA and 24 complex MwA) and 32 healthy controls] with 340 different features used for the algorithm training. The results show that an algorithm based on post-processed MRI data yields a high classification accuracy (97%) of MwA patients and precise distinction between simple MwA and complex MwA with an accuracy of 98%. Additionally, the sets of features relevant to the classification were identified. The feature importance ranking indicates the thickness of the left temporal pole, right lingual gyrus, and left pars opercularis as the most prominent markers for MwA classification, while the thickness of left pericalcarine gyrus and left pars opercularis are proposed as the two most important features for the simple and complex MwA classification. This method shows significant potential in the validation of MwA diagnosis and subtype classification, which can tackle and challenge the current treatments of MwA.


Rat prostate tumors express cancer procoagulant, an activator of coagulation factor X.
Two common procoagulant activities associated with tumors are tissue factor and cancer procoagulant (CP), an activator of coagulation factor X. We have identified a convenient source of CP in transplanted Lobund-Wistar rat PA3 prostate tumors. CP activity was purified from 5 independent transplanted prostate tumors by column chromatography. The protein activated factor X in the absence of TF and factor VII. An antihuman CP antibody recognized rat CP in an ELISA and inactivated CP activity in a chromogenic assay. Lobund-Wistar prostate tumors may provide a convenient animal model useful in determining the role of CP in cancer development.


[Breathing sleep disturbances and occupational medicine: study of 20 clinical cases].
During 2004, in the Center for Sleep Disorders, a questionnaire including Epworth sleepiness scale (ES) was administered to 120 subjects; 20 male subjects of this group with elevated score (ES >14) were selected and submitted to polysomnography. Subjects, all in working age, were represented by 3 (15%) shift-workers, 9 (45%) drivers, 17 (85%) industrial workers (among those 5 building workers) and 3 (15%) employers. By polysomnography, moderatelsevere OSAHS was diagnosed in all subjects (40% moderate, 60% severe). CPAP (Continuous Positive Airway Pressure) therapy led to an improvement of clinical symptoms since the first month. Counselling of Occupational Medicine Physician with the Center for Sleep Disorders, was useful to direct the action of Competent Doctor, especially for jobs requiring high vigilance (drivers or shift-worker). The pass certificate for jobs with an high risk (alone, in high places, heavy means drivers) cannot avoid to evaluate this pathology, that is often associated to other related risk factors (obesity, hypertension, diabetes), because it compromises both the specific suitability and the protection of common health and safety.


A rapid assessment of the implementation of integrated disease surveillance and response system in Northeast Nigeria, 2017.
Integrated disease surveillance and response (IDSR) is the strategy adopted for public health surveillance in Nigeria. IDSR has been operational in Nigeria since 2001 but the functionality varies from state to state. The outbreaks of cerebrospinal meningitis and cholera in 2017 indicated weakness in the functionality of the system. A rapid assessment of the IDSR was conducted in three northeastern states to identify and address gaps to strengthen the system. The survey was conducted at the state and local government areas using standard IDSR assessment tools which were adapted to the Nigerian context. Checklists were used to extract data from reports and records on resources and tools for implementation of IDSR. Questionnaires were used to interview respondents on their capacities to implement IDSR. Quantitative data were entered into an MS Excel spreadsheet, analysed and presented in proportions. Qualitative data were summarised and reported by thematic area. A total of 34 respondents participated in the rapid survey from six health facilities and six local government areas (LGAs). Of the 2598 health facilities in the three states, only 606 (23%) were involved in reporting IDSR. The standard case definitions were available in all state and LGA offices and health facilities visited. Only 41 (63%) and 31 (47.7%) of the LGAs in the three states had rapid response teams and epidemic preparedness and response committees respectively. The Disease Surveillance and Notification Officers (DSNOs) and clinicians' knowledge were limited to only timeliness and completeness among over 10 core indicators for IDSR. Review of the facility registers revealed many missing variables; the commonly missed variables were patients' age, sex, diagnosis and laboratory results. The major gaps were poor documentation of patients' data in the facility registers, inadequate reporting tools, limited participation of health facilities in IDSR and limited capacities of personnel to identify, report IDSR priority diseases, analyze and interpret IDSR data for decision making. Training of surveillance focal persons, provision of IDSR reporting tools and effective supportive supervisions will strengthen the system in the country.


[Current Cancer Immunotherapy Using Activated Lymphocytes - Do Lymphocytes Actually Recognize Cancer Cells ?].
Molecular cloning of interleukin-2(IL-2)has enabled adoptive cell therapy(ACT)to be established by using autologous activated lymphocytes. The low of regenerative medicine will promote the active development of ACT for public use, and ACTs that utilize tumor-infiltrating lymphocytes(TIL), in vitro tumor-sensitized lymphocytes, natural killer T cells, and gammadelta T cells are being evaluated as advanced medical treatments in Japan. In addition, chimeric antigen receptor genemodified T(CAR-T)cells and T cell receptor gene-modified T(TCR-T)cells are available for investigational clinical use. CART and TCR-T cells have been associated with serious adverse events as well as drastic clinical efficacies, indicating the importance of choosing the antigens to be targeted. Presently, it is accurate to state that lymphocytes do recognize cancer cells. Clinical ACT research focusing on TIL and mutated cancer antigens will be initiated for the development of personalized immunotherapy for cancer in the future.


Trichilemmal carcinoma occurring in a lesion of solar keratosis.
A case of trichilemmal carcinoma occurring in a lesion of solar keratosis was reported. A 92-year-old woman had an erythematous plaque on her face that contained a reddish nodule. Histological examination of the nodule revealed typical features of trichilemmal carcinoma accompanied by those of solar keratosis in the marginal zone. The histological features of the erythematous plaque corresponded with those of solar keratosis. However, in situ the carcinoma developed in the epithelium of a hair follicle as well as in the interfollicular epidermis in the lesion of solar keratosis. We considered it likely that bowenoid malignant transformation occurred in both interadnexal and adnexal epithelium because of actinic damage, and a trichilemmal carcinoma arose. The paper also discussed the histogenesis of trichilemmal carcinoma.


Characterization of Three L-Asparaginases from Maritime Pine (Pinus pinaster Ait.).
Asparaginases (ASPG, EC 184.108.40.206) catalyze the hydrolysis of the amide group of L-asparagine producing L-aspartate and ammonium. Three ASPG, PpASPG1, PpASPG2, and PpASPG3, have been identified in the transcriptome of maritime pine (Pinus pinaster Ait.) that were transiently expressed in Nicotiana benthamiana by agroinfection. The three recombinant proteins were processed in planta to active enzymes and it was found that all mature forms exhibited double activity asparaginase/isoaspartyl dipeptidase but only PpASPG1 was able to catalyze efficiently L-asparagine hydrolysis. PpASPG1 contains a variable region of 77 amino acids that is critical for proteolytic processing of the precursor and is retained in the mature enzyme. Furthermore, the functional analysis of deletion mutants demonstrated that this protein fragment is required for specific recognition of the substrate and favors enzyme stability. Potassium has a limited effect on the activation of maritime pine ASPG what is consistent with the lack of a critical residue essential for interaction of cation. Taken together, the results presented here highlight the specific features of ASPG from conifers when compared to the enzymes from angiosperms.


Introduction of a simulation model for choledocho- and pancreaticojejunostomy.
Pancreaticoduodenectomy includes choledochojejunostomy and pancreaticojejunostomy, which require hand-sewn anastomoses. Educational simulation models for choledochojejunostomy and pancreaticojejunostomy have not been designed. We introduce a simulation model for choledochojejunostomy and pancreaticojejunostomy created with a skin closure pad and a vascular model. A wound closure pad and a vein model (4 mm diameter) were used as a stump model of the pancreas. Pancreaticojejunostomy was simulated with a stump model of the pancreas and a double layer bowel model; these models were stabilized in an end-to-side fashion on a magnetic board using magnetic clips. In addition, vein (6 or 8 mm diameter) and bowel models were used to simulate choledochojejunostomy. Pancreatic and hepatobiliary surgery are relatively rare, particularly in a community hospital although surgical residents wish to practice these procedures. Our simulator enables surgeons and surgical residents to practice choledocho- and pancreaticojejunostomy through open or laparoscopic approaches.


Endocrine-disrupting chemicals and obesity risk: A review of recommendations for obesity prevention policies.
Emerging evidence indicates that industrially produced endocrine-disrupting chemicals (EDCs) may be as obesogenic as poor dietary patterns and should be considered in obesity prevention policies. The authors conducted two reviews: (a) a systematic search of four electronic databases for papers published since January 2010 to identify the policy recommendations contained in scientific reviews of EDC exposure and obesity risk and (b) a narrative review of obesity policy documents published since January 2012 to identify the recommendations of national and international agencies. A search of four electronic databases found 63 scientific reviews with policy recommendations, of which 26 suggested individual responsibility to avoid exposure, 11 suggested medical interventions to counter the effects of exposure, and 42 suggested regulatory control of hazardous chemicals. Of sixty policy documents examined, six mentioned pollutants as a possible risk factor for obesity, and only one made explicit reference to strategies for reducing exposure to EDCs. The UN Sustainable Development Goals include targets to prevent ill health from hazardous chemicals (Targets 3.9 and 12.4) and to remove unsafe industrial chemicals from the environment (Targets 6.3, 11.6, 12.4, and 14.1). The authors suggest these should be explicitly linked to World Health Assembly targets to halt the rise in obesity.


Collective Poisson process with periodic rates: applications in physics from micro-to nanodevices.
Continuous reductions in the dimensions of semiconductor devices have led to an increasing number of noise sources, including random telegraph signals (RTS) due to the capture and emission of electrons by traps at random positions between oxide and semiconductor. The models traditionally used for microscopic devices become of limited validity in nano- and mesoscale systems since, in such systems, distributed quantities such as electron and trap densities, and concepts like electron mobility, become inadequate to model electrical behaviour. In addition, current experimental works have shown that RTS in semiconductor devices based on carbon nanotubes lead to giant current fluctuations. Therefore, the physics of this phenomenon and techniques to decrease the amplitudes of RTS need to be better understood. This problem can be described as a collective Poisson process under different, but time-independent, rates, τ(c) and τ(e), that control the capture and emission of electrons by traps distributed over the oxide. Thus, models that consider calculations performed under time-dependent periodic capture and emission rates should be of interest in order to model more efficient devices. We show a complete theoretical description of a model that is capable of showing a noise reduction of current fluctuations in the time domain, and a reduction of the power spectral density in the frequency domain, in semiconductor devices as predicted by previous experimental work. We do so through numerical integrations and a novel Monte Carlo Markov chain (MCMC) algorithm based on microscopic discrete values. The proposed model also handles the ballistic regime, relevant in nano- and mesoscale devices. Finally, we show that the ballistic regime leads to nonlinearity in the electrical behaviour.


Increasing children's fruit and vegetable consumption: a peer-modelling and rewards-based intervention.
To evaluate a peer-modelling and rewards-based intervention designed to increase children's fruit and vegetable consumption. Over a 5-month period, children in an experimental and a control school were presented with fruit and vegetables at lunchtime. Children aged 5-7 y also received fruit at snacktime (mid-morning). The intervention was implemented in the experimental school and levels of fruit and vegetable consumption were measured at baseline, intervention and at 4-month follow-up. Two inner-city London primary schools. In total, 749 children aged 5-11 y. Over 16 days children watched video adventures featuring heroic peers (the Food Dudes) who enjoy eating fruit and vegetables, and received small rewards for eating these foods themselves. After 16 days there were no videos and the rewards became more intermittent. Consumption was measured (i) at lunchtime using a five-point observation scale; (ii) at snacktime using a weighed measure; (iii) at home using parental recall. Compared to the control school, lunchtime consumption in the experimental school was substantially higher at intervention and follow-up than baseline (P<0.001), while snacktime consumption was higher at intervention than baseline (P<0.001). The lunchtime data showed particularly large increases among those who initially ate very little. There were also significant increases in fruit and vegetable consumption at home (P<0.05). The intervention was effective in bringing about substantial increases in children's consumption of fruit and vegetables.


Does renal tubular dysfunction account for the enhanced CAm/CCr ratio in acute pancreatitis?
To verify whether renal tubular dysfunction may account for the CAm/CCr enhancement in acute pancreatitis (AP), we have measured the renal excretion of amylase, lysozyme, and gamma-glutamyl-transpeptidase (GGTP) in 22 patients with AP and in 8 with acute tubular necrosis. While the CAm/CCr ratio was elevated in most patients with AP, the CLys/CCr ratio fell within the normal range in 60% of these patients. The subdivision of patients with AP in subgroups with elevated and normal CLys/CCr ratios revealed a mean CAm/CCr not statistically different. Moreover, no correlation was present in AP between amylase vs. both lysozyme and GGTP clearances. These data suggest that tubular dysfunction does occur in some but not in all the patients with AP and seems not to play a major role in the pathogenesis of the increased CAm/CCr ratio in this condition.


The prognostic value of facial electroneurography in Bell's palsy.
Twenty six patients with Bell's palsy were studied at presentation using electroneurography. Ninety-four per cent of those who recovered completely could have been predicted by ENoG within 10 days of onset. Of the 18 patients who recovered completely, 13 had a total palsy at presentation.


Apelin, Omentin-1, and Vaspin in patients with essential hypertension: association of adipokines with trace elements, inflammatory cytokines, and oxidative damage markers.
Hypertension (HT) is a disease associated with endothelial dysfunction which is related to some adipokines and pro- and anti-inflammatory cytokines. Our aim was to investigate roles of apelin, omentin-1, and vaspin in essential HT and to evaluate their relationships with other pro- and anti-inflammatory cytokines, trace elements, and oxidative stress. We also investigated these parameters to determine asymptomatic target organ damage period and grading essential hypertension. One hundred fifty-three patients diagnosed with essential hypertension and 45 healthy controls were included in the study. Hypertension was defined as a systolic blood pressure > 140 mmHg and/or a diastolic blood pressure > 90 mm Hg or current use of an antihypertensive medication. The patients who had secondary HT, other chronic metabolic, cardiovascular, cerebrovascular diseases were excluded. History and physical exam including detailed cardiovascular examination were performed in all participants. Adipokines, cytokines, trace elements, lipid peroxidation, and ischemia-modified albumin levels were measured in blood samples by biochemical methods. Vaspin, IL-4, IL-8, IL-10, selenium, and zinc levels were significantly lower in the HT group compared to healthy controls while omentin-1, TNF-α, copper, iron, MDA, SOD, and IMA-C levels were significantly higher in HT patients compared to controls. Multiple ordinal regression revealed that TNF-α, IL-10, and body mass index of patients were statistically significant independent predictors (P = 0.024, P = 0.019, and P = 0.032, respectively) for grading of HT. IL-4 and IL-10 were significantly higher in patients with asymptomatic target organ damage, compared to patients without asymptomatic target organ damage (P = 0.032 and P = 0.015, respectively). Our findings suggest that adipokines apelin, omentin, and vaspin may be involved in hypertension by a complex interaction with the anti- and pro-inflammatory cytokines, trace elements, and oxidative stress pathways.


A further characterization of the selective K movements observed in human red blood cells following acetylphenylhydrazine exposure.
Following brief exposure to acetylphenylhydrazine, the potassium permeability of the human erythrocyte membrane is selectively augmented. While a similar increase in potassium permeability results from the intracellular accumulation of calcium (the Gardos phenomenon), we have found a number of features that allow these two pathways to be distinguished from one another. The acetylphenylhydrazine pathway does not require calcium for its activation, and can be seen even in the presence of a molar excess of the calcium chelator EGTA. The transmembrane potassium movement via this channel has a specific requirement for the anion chloride, and it can be inhibited by furosemide. The potassium that moves through the Gardos pathway, on the other hand, can be accompanied by any permeant anion, and is inhibitable by quinidine or cetiedil. Thus, acetylphenylhydrazine exposure seems to promote K + Cl cotransport, whereas the Gardos pathway represents a potassium conductive channel. While full demonstration of both these pathways requires harsh in vitro manipulation, the large electrochemical potassium gradient favoring the movement of this cation out from the erythrocyte suggests that even a partial activation of either pathway could cause intracellular dehydration and thus contribute importantly to the pathophysiology of in vivo red cell destruction.


[Headache: a rare manifestation of angina pectoris].
Typical angina pectoris rarely produces pain above the mandible. We report a patient with exertional headache, which was relieved by nitrates and revascularisation. The explanation is speculative; 1) anatomic convergence of cardiac nerve fibres and somatic efferents from the head; 2) increased intracranial pressure secondary to decreased cardiac output during ischaemia; and 3) unidentified headache eliciting mediators released by cardiac ischaemia. We conclude that headache may be a (the only) manifestation of myocardial ischaemia. The suspicion should arise, if the headache is exercise-induced and relieved by nitrates.


Simplified Roux-en-Y reconstruction after laparoscopic radical distal gastrectomy for gastric cancer.
Although there were a variety of strategies for the alimentary tract reconstruction of patients with gastric cancer who underwent laparoscopic radical distal gastrectomy, it remains controversial regarding which procedure is optimal. We developed a simple technique for Roux-en-Y reconstruction during laparoscopic surgery and evaluated its technical feasibility and safety. Seventy-one cases of modified Roux-en-Y reconstructions after laparoscopic radical distal gastrectomy were consecutively performed in our hospital, from November 2020 to March 2022. A retrospective review of medical data was conducted. Intraoperative and postoperative outcomes, including operation time and incidence of postoperative complications, were collected and analyzed. All procedures of laparoscopic distal gastrectomy with D2 lymph node dissection were successfully completed without any intraoperative complication. The mean number of retrieved lymph node was 38.8 ± 10.6. Mean operative time was 223.5 ± 42.4 min, whereas intraoperative blood loss was 102.2 ± 96.3 ml. No postoperative mortality was recorded. Six patients (8.5%) experienced postoperative complications and were managed conservatively. In addition, only two patients (2.8%) required rehospitalization during a median short-term follow-up period of 6 months. The modified method is a simple and safe approach for laparoscopic radical distal gastrectomy.


[A new era in neuroradiology. Computerised axial transverse tomography-C.A.T.T. (Emi-Scanner) and its applications (author's transl)].
With an adequate follow-up, the authors report their experience with computerised axial transverse tomography (Emi-Scanner) after its use in 500 cases. A description of the method is followed by an account of the material used in this study. They mention the safety of C.A.T.T. and the profound change which this new technique has brought about in the chronology of neuroradiological investigations. The applications of C.A.T.T. are defined in relation to conventional neuroradiological investigations. In traumatic, degenerative, infective, neoplastic and vascular disorders, as well as epilepsy, C.A.T.T. makes possible visualisation of the lesion in the majority of cases. Having dealt with each of these indications, the authors illustrate the typical appearances seen at C.A.T.T. by significant examples. C.A.T.T. reduces the proportion of angiographic and encephalographic examinations. This tendency will become even more marked with the advent of technical development which improve the power of resolution of C.A.T.T.


Vibrational spectral diffusion of azide in water.
Vibrational spectral diffusion denotes the time-dependent fluctuations of a solute's vibrational frequencies due to local environmental dynamics. Vibrational line shapes are weakly sensitive to spectral diffusion, whereas three-pulse vibrational echoes are much more sensitive. We report here on theoretical studies of spectral diffusion of the asymmetric stretch of the azide anion in heavy water. We run a classical molecular dynamics simulation of rigid azide in rigid water, and at every time step we calculate the azide's anharmonic asymmetric stretch frequency using an optimized quantum mechanics/molecular mechanics method developed earlier. This generates a frequency trajectory, which we use to calculate the absorption line shape and integrated three-pulse echo intensity. Our results for both the line width and the integrated echo intensity are in excellent agreement with experiment. Our calculated frequency time-correlation function is in excellent agreement with experiment for long times (greater than 250 fs) but differs considerably from experiment at short times; our theoretical correlation function has a very pronounced oscillation, presumably due to intermolecular azide-water hydrogen-bond stretching dynamics.


Latency in onset of decompression sickness on direct ascent from air saturation.
Twenty-four human subjects were exposed to compressed air at simulated depths ranging from 45 ft seawater gauge (fsw) (2.36 ATA) to 75 fsw (3.27 ATA) for periods of time sufficient to allow saturation of most tissues with inert gas. From each of four depths (45, 55, 65 and 75 fsw), subjects ascended directly to 1 ATA, where they remained for 30, 17, 13, and 10 min, respectively. During this time the onset of Doppler detected venous gas emboli (VGE), pruritus, and any other symptomatology was monitored and recorded. In the ascending excursion from 45 fsw (n = 18), the mean appearance times of pruritus and VGE were 19.3 +/- 7.5 (mean +/- SD) and 21.9 +/- 7.4 min, respectively, with one case of pain-only decompression sickness (DCS). The excursion from 55 fsw (n = 17) shortened these times to 9.2 +/- 3.3 and 14.4 +/- 3.2 min, respectively, with two cases of DCS, one each of pain-only and serious types. In the excursion from 65 fsw (n = 23), mean pruritus and VGE appearance times were 6.3 +/- 1.4 and 10.8 +/- 1.9 min, respectively, with no cases of DCS. The excursion from 75 fsw (n = 6) resulted in appearance times of 4.8 +/- 0.8 and 8.2 +/- 1.2, respectively, with one case of pain-only DCS. Sufficient cases of DCS did not occur in any of the excursions to allow determination of mean appearance times. The relationship between pressure reduction and appearance times of pruritus and VGE, and the threshold time of DCS, can be described mathematically. We conclude that latency in the development of DCS on direct ascent from air saturation exists and is of sufficient magnitude to permit practical application in emergency decompressions or unpressurized transfers between compressed air or N2-O2 environments.


Quantification of single fluid inclusions by combining synchrotron radiation-induced micro-X-ray fluorescence and transmission.
Fluid inclusions represent the only direct samples of ancient fluids in many crustal rocks; precise knowledge of their chemical composition provides crucial information to model paleofluid-rock interactions and hydrothermal transport processes. Owing to its nondestructive character, micrometer-scale spatial resolution, and high sensitivity, synchrotron radiation-induced micro-X-ray fluorescence has received great interest for the in situ multielement analysis of individual fluid inclusions. Major uncertainties associated with the quantitative analysis of single fluid inclusions arise from the inclusion depth and the volume of fluid sampled by the incident beam. While the depth can be extracted directly from the fluorescence spectrum, its volume remains a major source of uncertainty. The present study performed on natural and synthetic inclusions shows that the inclusion thickness can be accurately evaluated from transmission line scans. Experimental data matched numerical simulations based on an elliptical inclusion geometry. However, for one nonelliptical inclusion, the experimental data were confirmed using a computed absorption tomography reconstruction. Good agreement between the imaging and scanning techniques implies that the latter provides reliable fluid thickness values independent of the shape of the inclusion. Taking into consideration the incident angle, the incident beam energy, the inclusion fluid salinity, and the transmission measurement stability resulted in errors of 0.3-2 microm on calculated fluid inclusion thicknesses.


Vocabulary of preschool children with typical language development and socioeducational variables.
To investigate the correlation between age, socioeconomic status (SES), and performance on emissive and receptive vocabulary tests in children with typical language development. The study sample was composed of 60 preschool children of both genders, aged 3 years to 5 years 11 months, with typical language development divided into three groups: G I (mean age=3 years 6 months), G II (mean age=4 years 4 months) and G III (mean age=5 years 9 months). The ABFW Child Language Test - Vocabulary and the Peabody Picture Vocabulary Test (PPVT) for emissive and receptive language were applied to the preschoolers. The socioeconomic classification questionnaire of the Brazilian Association of Survey Companies (ABEP) was applied to the preschoolers' parents/legal guardians. Data were analyzed according to the criteria of the aforementioned instruments and were arranged in Excel spreadsheet for Windows XP®. A multiple linear regression model was used, adopting a statistical significance level of 5%, to analyze the correlation between age, SES, and performance on the receptive and emissive vocabulary tests. In the ABEP questionnaire, participants were classified mostly into social level C (63.3%), followed by levels B (26.6%) and D (10%). The preschoolers investigated presented emissive and receptive vocabulary adequate for the age groups. No statistically significant difference was found for the variables age and SES regarding emissive and receptive vocabulary. Higher test scores were observed with increased age and SES, for social levels "B" compared with "D" and for "C" with "D". The variables age and socioeconomic status influenced the performance on emissive and receptive vocabulary tests in the study group.


[Surgery on articular cartilage: from debridement to tissue engineering].
Articular cartilage is a complex tissue with a limited endogenous repair capacity. Surgical strategies to stimulate repair of damaged cartilage are presently evolving extensively. New techniques based on tissue-engineering principles with cultured cells and scaffolds are challenging established techniques based on generating a repair response from the bone marrow. This paper reviews treatments such as debridement, marrow-stimulating techniques, osteochondral transplantation and autologous chondrocyte transplantation. Debridement and marrow stimulation can provide significant relief of symptoms. Recently, randomized studies have uncovered some of the clinical effects of the new biotechnology-based surgical methods. However, no significant advances over the established surgical techniques have been developed.


Optimized Zernike Term Selection in Customized Treatments for Laser Corneal Refractive Surgery: Case Report
To report a case in which a tissue saving program in an aberrated eye was used. A new algorithm for the selection of an optimized set of Zernike terms in customized treatments for laser corneal refractive surgery was developed and clinically tested. Ablation was performed using the SCHWIND ESIRIS excimer laser. Pre- and postoperative corneal wave aberrations were analyzed using the Keratron Scout videokeratoscope (Optikon 2000). Required ablation was reduced by approximately 15% compared to full customized correction. Refraction was corrected to subclinical levels, uncorrected distance visual acuity improved to 20/20, corrected distance visual acuity gained 2 lines, aberrations were reduced by approximately 40% compared to preoperative baseline levels, and the functional optical zone of the cornea was enlarged by approximately 40% compared to preoperative baseline levels. Trefoil, coma, spherical aberration, and the root-mean-square value of the higher order aberrations were reduced. Eliminating all higher order aberrations may not optimize visual function in highly aberrated eyes. The new algorithm minimized tissue removal in refractive surgery but further clinical evaluations are required to confi rm preliminary results.


Transient Inactivation of Shell Part of Nucleus Accumbens Inhibits and Exacerbates Stress-Induced Metabolic Alterations in Wistar Rats.
The role of different parts of the extended amygdala in metabolic signs of stress is not well understood. In the present study, we decided to evaluate the impact of the shell part of nucleus accumbens (NAc) on metabolic disturbance induced by electro foot shock stress using transient inactivation method in the rat. Male Wistar rats (W: 230-250 g) were canuulated unilaterally in the shell part of nucleus accumbens and left one week for recovery. Five minutes before each stress session, the animals either received sterile saline (0.25 μl/side) (control) or lidocaine 2% (0.25 μl/side) (experiment). Blood samples were taken from rats' retro-orbital sinus for plasma corticosterone measurements. In addition, animals' weight gain, food and water intake, locomotor activity, and rearing were recorded. Stress reduced weight gain and food intake, increased water intake and plasma corticosterone level, and reduces locomotor activity and rearing. Transient inactivation of the right side of the NAc inhibits the stress effect on weight gain, water intake and plasma corticosterone level, but not food intake. However, when the left side of the NAc was inactivated, only weight gain was affected and other parameters were not differing from stress group. Even thought, the plasma corticosterone level was elevated. In conclusion, our data indicated that right side of shell part of NAc transient inactivation leads to reduction in metabolic signs of stress but left side of shell part of the NAc inactivation even exacerbates stress signs.


Genomic characterization and molecular evolution of human monkeypox viruses.
Monkeypox virus is a member of the family Poxviridae, as are variola virus and vaccinia virus. It has a linear double-strand DNA genome approximately 197 kb long, containing ~190 non-overlapping ORFs. Comparison of members of the Central and West African clades shows the presence of unique genes that are associated with different disease presentations, depending on the strain. The last smallpox vaccination efforts ended in the mid-1980s, and there is concern about the recent spread of human monkeypox disease around the world. Almost 87,000 human monkeypox cases have been diagnosed in the world, of which more than 10,900 were in Brazil. The aim of this study was to evaluate the epidemiology and molecular evolution of hMpxV. From computational biology analysis of 640 hMpxV genomes from 1962 to 2022, synteny breaks and gene conservation were observed between Central and West clade genomes, and strains belonged with the 2022 outbreak assigned to the West African clade. Evidence was found for diversifying selective pressure at specific sites within protein coding sequences, acting on immunomodulatory processes. The existence of different sites under diversifying and purifying selection in paralog genes indicates adaptive mechanisms underlying the host-pathogen interaction of monkeypox virus in humans.


Microscope-based augmented reality with diffusion tensor imaging and fluorescein in insular glioma resection.
Maximal safe resection is the goal of insular glioma surgery. The combination of intraoperative augmented reality (AR) diffusion tensor imaging (DTI) fiber tracking with fluorescein dye (F) helps achieve this goal throughout a microscope-based visualization of the tumor and white matter fiber tracts. The aim of the present video article was to show the technical key aspects of DTI-F microscope-based AR-assisted surgery during the gross-total resection of an insular Berger-Sanai type I+IV high-grade glioma in a 63-year-old patient, performed through a pterional transsylvian approach. The video can be found here: https://stream.cadmore.media/r10.3171/2021.10.FOCVID2157.


Hypalgesia effect of IL-24, a quite new mechanism for IL-24 application in cancer treatment.
Tumor suppressor melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) has been extensively regarded as an anti-oncogene; however, that whether IL-24, as a member of IL-10 family, is involved in cancer pain was seldom reported before. In this study, we found that IL-24 mediated by adenovirus could significantly increase the plantar mechanical pain threshold in both operation side and contralateral side of the animal models, which were established by injecting 5×103 Walker 256 rat breast cancer ascitic tumor cells into rats' tibia bone medullary canals; IL-24 could also suppress in vitro Walker 256 cells growth by inducing cell apoptosis. Pathologically, IL-24 could protect bone trabecula and substantia corticalis ossium from being completely destructed. Enzyme-linked immunosorbent assay (ELISA) showed that IL-24 treatment could increase the β-endorphin levels and decrease the IL-6 concentration in plasma of animals. Our study indicated that IL-24 has a potential treatment effect on cancers not only by inhibiting tumor proliferation, but also by the promotion of β-endorphin synthesis, inhibition of IL-6 secretion to relieve cancer pain.


Circulating Stem Cells Associate With Adiposity and Future Metabolic Deterioration in Healthy Subjects.
Obesity and metabolic syndrome are associated with mild leukocytosis, but whether hematopoietic stem/progenitor cells (HSPCs) play a role in metabolic deterioration is unknown. Our objective was to analyze the cross-sectional and longitudinal associations between CD34(+) HSPCs, adiposity, and metabolic syndrome features. This is a cross-sectional study on 242 participants, 155 of whom were followed and included in a longitudinal assessment. This study took place in a tertiary referral center for metabolic diseases. Healthy working individuals attending a cardiovascular screening program (total n = 3158) and having a baseline measure of circulating CD34(+) cells participated. We collected demographic and anthropometric data, cardiovascular risk factors, and metabolic syndrome parameters. Participants (34.7% males, mean age 45.9 ± 0.5 years) were free from diabetes and cardiovascular disease. Cross-sectionally, absolute CD34(+) cell counts were directly correlated with body mass index and waist circumference, inversely correlated with high-density lipoprotein cholesterol and the quantitative insulin sensitivity check index, and were higher in individuals with the metabolic syndrome. The hematopoietic component contributed most to the association of CD34(+) cells with adiposity. During a 6.3-year follow-up, high absolute levels of CD34(+) cells were associated with increasing waist circumference, declining quantitative insulin sensitivity check index and high-density lipoprotein cholesterol, and with incidence of metabolic syndrome. Relative CD34(+) cell counts showed weaker associations with metabolic parameters than absolute levels, but were longitudinally associated with increasing waist circumference and metabolic syndrome development. A mild elevation of circulating CD34(+) progenitor cells, reflecting expansion of HSPCs, is associated with adiposity and future metabolic deterioration in healthy individuals.


Comparison of recombinant human erythropoietin and darbepoetin alpha in children.
The aim was to compare the clinical efficacy of recombinant human erythropoietin (rHuEPO) and darbepoetin alpha (DA) in the treatment of anemia in children with chronic kidney disease (CKD). Thirty-four (13 female, 21 male) CKD patients were enrolled in the study. Mean age was 11.42 ± 4.05 years. Nine patients were on hemodialysis, 18 were on peritoneal dialysis and seven patients were in CKD stage 4. Seventeen patients received rHuEPO and the remaining 17 patients received DA. Hemoglobin (Hb) was not significantly different between the two groups during monthly follow up and at the end of 6 months (P > 0.05), but there was a significant increase within each group at the end of 6 months (P = 0.01 for rHuEPO; P = 0.02 for DA). Hb was not different between the patients on and not on dialysis in both groups at the end of the study (P > 0.05). The efficacy of the s.c. and i.v. routes was similar within each group (P > 0.05). Systolic hypertension was observed in only one patient in the DA group, no other adverse effect was observed in either groups. DA is a reasonable alternative to rHuEPO in the treatment of anemia in pediatric CKD patients, due to its clinical efficacy, convenience of use, patient compliance and tolerability.


[Localized tracheobronchial amyloidosis. A new case studied with x-ray computed tomographic and nuclear magnetic resonance. Review of the literature].
We report a new case of localized primary tracheobronchial amyloidosis revealed by haemoptysis and effort dyspnea. The CT scan image was a homogeneous and circumferential thickening of the bronchial wall measuring 282 on the Hounsfield scale. At magnetic resonance imaging the amyloid substance was a slightly less intense than fat tissue in T1 and T2-weighted sequences. Treatment using Yag laser photoresection stabilized the lesions with one year follow-up. The review of the literature enables us to summarize the clinical, endoscopic, morphological, prognostic and therapeutic features of tracheobronchial amyloidosis, as well as pathogenic hypotheses and relationship with tracheobronchopathia osteoplastica.


Simultaneous Determination of Naturally Occurring Estrogens and Mycoestrogens in Milk by Ultrahigh-Performance Liquid Chromatography-Tandem Mass Spectrometry Analysis.
A simple, fast, and reproducible method for the simultaneous determination of natural estrogens and mycoestrogens (resorcylic acid lactones) in milk by ultrahigh-performance liquid chromatography combined with electrospray ionization triple quadrupole tandem mass spectrometry (UHPLC/ESI-MS/MS) is described. The extraction was carried out by solid-phase extraction (SPE) using graphitized carbon black as solid sorbent. The use of carbon black allowed us to avoid any type of sample pretreatment, and the extraction was performed simply by diluting milk samples in water. Correlation coefficient values were obtained in the range between 0.9991 and 1, with good recoveries (67-107% at the lowest spiked level), repeatability (4.8-16.8%), and reproducibility (3.2-16.3%). Moreover, a very low matrix effect was observed for both estrogens and mycoestrogens. With respect to a previous method based on SPE with Oasis MAX cartridges, the one here described allowed us to detect all the analytes under investigation, at the lowest tested concentration level, including free estrogens (in particular estriol). Finally, the developed UHPLC/ESI-MS/MS method was applied to the analysis of some whole milk samples from different lactating animals (cow, goat, and donkey) as well as ultrahigh-temperature-treated cow milk and powder milk samples.


Diffusion into use of exenatide for glucose control in diabetes mellitus: a retrospective cohort study of a new therapy.
Exenatide was approved by the US Food and Drug Administration (FDA) in April 2005 as adjunctive therapy to metformin or a sulfonylurea for the treatment of type 2 diabetes mellitus (DM). We evaluated whether use of exenatide soon after its approval was consistent with the FDA- approved indications. We assembled a retrospective cohort of patients with DM using data from a population of employed persons and their dependents, including pharmacy claims and claims for inpatient and outpatient services, provided by i3 Innovus. The data set included patients aged between 18 and 64 years with a diagnosis of DM or a claim for a DM drug from June 1, 2004, to December 31, 2005. Laboratory data were available for a subgroup of patients tested at specific commercial laboratories from June 1, 2003, to December 31, 2005. In addition, we requested data for patients with a diagnosis of obesity, regardless of a diagnosis of DM, to assess early off-label use of this medication. Patients were categorized by DM medication use and by their first fill date for exenatide, and their clinical characteristics were described. Early use was defined as filling a prescription for exenatide in the first 3 months after its approval. For descriptive purposes, we reported the means and percentages for the variables described. The study included data for 206,345 individuals (mean age, 51.3 years), of whom 54.0% were male. Starting in June 2005, prescriptions for exenatide were filled by 3225 (1.6%) individuals. Fifty-three percent of early users were women. Among those who filled a prescription for exenatide, 21.9% were obese, compared with 10.9% to 15.1% of those filling prescriptions for other DM medications. The proportion of patients filling a prescription for exenatide who had not received a prescription for any other DM medication in the preceding year was 14%, suggesting that exenatide was their initial therapy. A prescription for a thiazolidinedione was filled by 29.9% of patients within 60 days of filling a prescription for exenatide. Soon after its approval, exenatide was frequently used as monotherapy or in combination with a thiazolidinedione, neither of which is an FDA- approved indication. The observation that those filling a prescription for exenatide had a higher prevalence of obesity than those receiving prescriptions for other therapies may reflect awareness of the weight-lowering effects of exenatide.


Differentiation of renal cell carcinoma subtypes through MRI-based radiomics analysis.
To explore whether clear cell renal cell carcinoma (ccRCC), papillary renal cell carcinoma (pRCC), and chromophobe renal cell carcinoma (cRCC) can be distinguished using radiomics features extracted from magnetic resonance (MR) images. Seventy-seven patients (ccRCC = 32, pRCC = 23, cRCC = 22) underwent MRI before surgery between May 2013 and August 2018 in this retrospective study. Thirty-nine radiomics features were extracted from tumor volumes on three sequences (T2WI, EN-T1WI CMP, and EN-T1WI NP). The Kruskal-Wallis test with Bonferonni correction and variance threshold were used for feature selection among the three RCC subtypes. ROC curves for the three subtypes were generated based on radiomics features. AUC, accuracy, sensitivity, and specificity for subtype differentiation are reported. Linear discriminant analysis (LDA) was used to assess the discriminative ability of these radiomics features. Significant radiomics features among the three subtypes were identified, and ROC curves achieved excellent AUCs for T2WI, EN-T1WI CMP, EN-T1WI NP, and combined three MR sequences (0.631, 0.790, 0.959, and 0.959 between ccRCC and cRCC; 0.688, 0.854, 0.909, and 0.955 between pRCC and cRCC; 0.747, 0.810, 0.814, and 0.890 between ccRCC and pRCC). In addition, LDA demonstrated the three RCC subtypes were correctly classified by radiomics analysis (66.2% for EN-T1WI CMP, 71.4% for EN-T1WI NP, 55.8% for T2WI, and 71.4% for the combined three MR sequences). Radiomics analysis can be used to differentiate among ccRCC, pRCC, and cRCC based on radiomics features extracted from multiple-sequence MRI and may help diagnose and treat RCC patients in the future, while further study is still needed. • Radiomics features on multiple-sequence MRI can help differentiate the three subtypes of renal cell carcinoma (clear cell, papillary renal cell, and chromophobe renal cell carcinoma). • Radiomics features based on MRI indicate greater textural heterogeneity on ccRCCs than pRCCs and cRCCs (the highest AUCs on EN-T1WI NP are 0.814 for ccRCCs vs pRCCs and 0.959 for ccRCCs vs cRCCs, respectively). • There is a significant difference in the textural heterogeneity of radiomics features between pRCCs and cRCCs (the AUC is 0.909, 0.854, and 0.688 on EN-T1WI NP, EN-T1WI CMP, and T2WI, respectively).


Current treatment options for asthma in adults.
Asthma is a common disorder with an increasing prevalence in the developed world. It is a serious health problem affecting health care costs, lost productivity, and death. Unfortunately, uncontrolled asthma is common and often unrecognized by physicians; of equal concern, uncontrolled asthma is accepted by asthmatic patients as they are uneducated as to what to expect from asthma therapy. Many learn to live with the limitations of daily activity and to overuse their rescue inhalers and yet when asked by their physicians, ''How's your asthma?'' the answer is ''okay''. The pursuit of more revealing questions regarding frequency in the use of rescue medications, nocturnal symptoms, activity limitations, and compliance with controller medications may be then overlooked. To achieve the goal of normal life on as few medications as possible will start with a well-educated patient. Understanding intermittent from persistent asthma and then tailoring the best regimen for each patient is imperative. The treatment options and the advances in the understanding of the pathophysiology of asthma in the past 3 decades have been remarkable. There are increasing resources for both physicians and patients available to facilitate a better understanding of asthma management and the several treatment options. Currently established guidelines are an excellent starting point for initiating therapy for intermittent and mild, moderate, and severe persistent asthma. The short-acting beta 2 agonists are first-line therapy for intermittent asthma, exercise-induced asthma, and acute exacerbations. Long-acting Beta 2 agonists, cromolyn and nedocromil, and leukotriene modifiers may also be used for exercise. Systemic corticosteroids may be needed for acute exacerbations. The treatment of choice for persistent asthma is ICS and, depending on the severity, add-on therapy with long-acting beta 2 agonists, theophylline, and leukotriene modifiers are next. Lastly, omalizumab, anti-IgE therapy, will make an important place for its use in certain persistent moderate and severe asthma. This will be particularly true if the cost of the medication is reduced in the future. Asthma control, morbidity, and mortality will improve with a careful and comprehensive medical regimen using the current multiple treatment options.


Over-expression of gene encoding heat shock protein 70 from Mycobacterium tuberculosis and its evaluation as vaccine adjuvant.
Heat shock proteins (Hsps) are evolutionary ancient and highly conserved molecular chaperons found in prokaryotes as well as eukaryotes. Hsp70 is a predominant member of Hsp family. Microbial Hsp70s (mHsp70s) have acquired special significance in immunity since they have been shown to be potent activators of the innate immune system and generate specific immune responses against tumours and infectious agents. The present study was aimed to clone express and purify recombinant Hsp70 from the Mycobacterium tuberculosis and characterise it immunologically. The study also aimed at determining the potential of recombinant M. tuberculosis heat shock protein (rMTB-Hsp70) as adjuvant or antigen carrier. Cloning of M. tuberculosis heat shock protein (MTB-Hsp70) amplicon was carried out using the pGEMT-Easy vector although for expression, pProExHTb prokaryotic expression vector was used. Purification of recombinant Hsp70 was carried out by nickel-nitrilotriacetic acid (Ni-NTA) affinity chromatography. For immunological characterization and determining the adjuvant effect of MTB-Hsp70, BALB/c mice were used. The data obtained was statistically analysed. Hsp70 gene was cloned, sequenced and the sequence data were submitted to National Center for Biotechnology Information (NCBI). Recombinant MTB-Hsp70 was successfully over-expressed using the prokaryotic expression system and purified to homogeneity. The protein was found to be immunodominant. Significant adjuvant effect was produced by the rMTB-Hsp70 when inoculated with recombinant outer membrane protein 31; however, effect was less than the conventionally used the Freund's adjuvant. Protocol standardised can be followed for bulk production of rHsp70 in a cost-effective manner. Significant adjuvant effect was produced by rMTB-Hsp70; however, the effect was than Freund's adjuvant. Further, studies need to be carried out to explore its applicability as carrier of antigen.


Extracellular galactosaminogalactan from Penicillium frequentans.
Penicillium frequentans secreted an exopolysaccharide composed mainly of N-acetyl-galactosamine (48.4%) and galactose, mannose and glucose in the ratio 4:1:1, that were alpha - (1----4) and alpha - (1----3) linked predominantly. Greater polysaccharide production was achieved in old cultures grown statically with glucose as carbon source.


In vitro evaluation of AZD2563, a new oxazolidinone, tested against beta-haemolytic and viridans group streptococci.
Linezolid was the first clinically applied agent from the oxazolidinone class, and AZD2563, a new agent, is described here. Five hundred and twenty-five streptococcal isolates were tested, including beta-haemolytic (266) and viridans group (259) species. MIC(50)/MIC(90)/% susceptible (susceptibility breakpoint <2 mg/L of AZD2563) results were, for beta-haemolytic species: AZD2563 (1/2/100), linezolid (1/2/100), quinupristin-dalfopristin (0.25/0.25/100), vancomycin (0.25/0.5/100) and levofloxacin (0.5/1/99); for viridans group species: AZD2563 (0.5/1/100), linezolid (1/1/100), quinupristin-dalfopristin (0.5/1/99), vancomycin (0.5/0.5/100) and levofloxacin (1/1/98). The modal MICs of AZD2563 and linezolid were 0.5 or 1 mg/L and 1 mg/L, respectively. AZD2563 activity screening against these non-pneumococcal streptococci indicated a slightly greater potency of AZD2563 when compared with linezolid. All AZD2563 MICs were <2 mg/L.


Escapism-Based Motivation Affected the Psychological Performances of High-Risk Internet Gaming Disorder Individuals.
Escapism-based motivation (EBM) is considered as one of the diagnostic criteria for internet gaming disorder (IGD). However, how EBM affects the high risk of IGD (HIGD) population remains unclear. An initial number of 789 college students participated in the general, internet gaming behavior, and motivation surveys. After multiple evaluations, 57 individuals were identified as HIGD (25 with EBM, H-EBM; 32 with non-EBM, H-nEBM). In addition, 51 no-gaming individuals were included as the control group (CONTR). The cohorts completed the psychological assessments and eye-tracking tests, and analyses of group differences, correlations, and influencing factors of the indicators were performed. The Barratt impulsiveness score of H-nEBM and H-EBM was significantly higher than that of CONTR (MD = 3.605, P = 0.017; MD = 3.744, P = 0.022). In addition, emotional intelligence self-emotion management ability was significantly lower in the H-EBM than in CONTR (MD = -2.038, P = 0.004). Correct rates and reaction times in the anti-saccade task differed significantly between the three groups (F = 3.525, P = 0.033; F = 4.459, P = 0.014). However, no differences were found in the comparison of the digital span test (DST), trail making test (TMT), animal verbal fluency test, Stroop test, and mental rotation test results. The anti-saccade test indicators were positively correlated with the DST results but negatively correlated with the Stroop test results (P < 0.05). Correct rates in the mental rotation test were negatively correlated with the TMT results but positively correlated with the DST results (P < 0.05). The participants with high Stroop test scores and no lover experience and who were raised by their grandparents were likely to develop EBM to engage in high risk of internet gaming disorder (P < 0.05). EBM has a significantly negative effect on impulsivity, self-emotion management ability, and response inhibition in the HIGD participants.


[Efficacy of ondansetron in the prevention of nausea and vomiting after laparoscopic cholecystectomy].
To assess the efficacy of 4 mg of intravenous ondansetron versus placebo for the prevention of postoperative nausea and vomiting (PONV) in cholecystectomy, a type of surgery that is highly emetic. A random, double blind, placebo controlled study of 40 women over 18 years of age who were scheduled for non urgent laparoscopic cholecystectomy under general anesthesia. The patients were assigned to two groups to receive ondansetron (n = 23) or placebo (n = 17). Premedication and anesthesia were similar for all. The severity of PONV in the first 24 hours after surgery was recorded. There were no significant differences between the two groups with respect to biological characteristics or other factors that might influence the presentation or severity of PONV. The percentage of PONV-free patients was significantly higher in the ondansetron group than in the control group (73.91 and 11.76%, respectively; p < 0.001). Intravenous administration of 4 mg ondansetron is significantly superior to placebo for PONV prophylaxis after laparoscopic cholecystectomy.


Widom line and dynamical crossovers as routes to understand supercritical water.
Supercritical water is fundamental in many fields of applications and a precise characterization of the supercritical state is of uttermost importance for this liquid. In a fluid, when moving from the critical point into the single-phase region, the thermodynamic response functions show maxima reminiscent of the critical divergence. Here we study the thermodynamic properties of water in the supercritical region by analysing both available experimental data and our computer simulation results. We find that the lines connecting the maxima of the response functions converge on approaching the critical point in a single line, the Widom line. We further show that the Widom line coincides with a crossover from a liquid-like to a gas-like behaviour clearly visible in the transport properties. These thermodynamic and dynamic features show that the supercritical state in water is far more complex than what was so far believed, indicating a new perspective in the characterization of the thermodynamics of this state.


Influence of nonionic surfactants on the potentiometric response of ion-selective polymeric membrane electrodes designed for blood electrolyte measurements.
The effect of the nonionic surfactants Brij 35 and Triton X-100 on the selectivity of neutral carrier-based ion-selective electrodes (ISEs) commonly used for measurements of electrolytes in whole blood is investigated. Studies are conducted with plasticized PVC membranes doped with several neutral ionophores commonly employed to prepare clinically useful potassium, calcium, and sodium ISEs. An observed increase in the electrodes' EMF values upon the addition of surfactant to the test solution suggests a change in the ion selectivity of the polymeric membranes in the presence of Brij 35 or Triton X-100. For membranes doped with K(+)-selective valinomycin, the effect of nonionic surfactants is relatively small. However, in the case of calcium-selective membranes prepared with ETH 1001 and ETH 129, nonionic surfactants, especially Triton X-100, decrease the selectivity for calcium over potassium cations by nearly 1 order of magnitude. Such behavior is even more dramatic for sodium-selective membranes, with the degree of surfactant-induced loss of ion selectivity dependent on the specific sodium ionophore employed, the lipophilic tetraphenylborate derivative content of the membrane, and the surfactant type. A detailed theoretical model is presented to explain the effect of nonionic surfactants on the EMF response function of cation-selective polymeric membrane electrodes. Experimental results are in good agreement with theoretical predictions based on known binding constants for ionophores and surfactants with given cations.


Disinfection of Burkholderia cepacia complex from non-touch taps in a neonatal nursery.
Burkholderia cepacia complex (Bcc) comprises nine closely related species or genomovars. It is an important causative agent of opportunistic infections and waterborne nosocomial infections. B. cepacia (formerly genomovar I) was identified from the blood culture of a baby in our neonatal unit (NU) in March 2005. B. cepacia was isolated four times from clinical specimens since the introduction of non-touch taps in the NU from 2000 to 2005 and only once from 1994 to 2000. Environmental samples were collected from the NU, including tap water from non-touch taps. Clinical and environmental isolates of Bcc were characterized using molecular identification and strain typing. A literature review was undertaken to delineate a method for eradication of Bcc. Several variations for hot water eradication of the organism from the taps were attempted. Genotyping and molecular analysis revealed that tap water isolates were B. cenocepacia which was a different species from the B. cepacia isolated from blood cultures of the neonate. However, B. cenocepacia has been known to cause nosocomial outbreaks and it was eventually eradicated from the NU by using repeated thermal shock (hot water at 65 degrees C for 10 min), changing taps and decolonizing sinks with hypochlorite. Molecular typing is useful in assisting the investigation of Bcc nosocomial infections.


Severe cardiac phenotype of Berardinelli-Seip congenital lipodystrophy in an infant with homozygous E189X BSCL2 mutation.
Berardinelli-Seip congenital lipodystrophy (BSCL) is a rare autosomal recessive condition associating insulin resistance, absence of subcutaneous fat and muscular hypertrophy. Disease-causing mutations have been described in AGPAT2 and BSCL2 genes. Hypertrophic cardiomyopathy is a classical late (third decade) complication which has only been occasionally described in childhood. We report on a 4-month-old Chinese male infant who presented with a severe BSCL "cardiac" phenotype comprising heart failure, hypertension and hypertrophic cardiomyopathy.


Biscalar Integrable Conformal Field Theories in Any Dimension.
We propose a D-dimensional generalization of 4D biscalar conformal quantum field theory recently introduced by Gürdogan and one of the authors as a particular strong-twist limit of γ-deformed N=4 supersymmetric Yang-Mills theory. Similar to the 4D case, the planar correlators of this D-dimensional theory are conformal and dominated by "fishnet" Feynman graphs. The dynamics of these graphs is described by the integrable conformal SO(1,D+1) spin chain. In 2D, it is the analogue of Lipatov's SL(2,C) spin chain for the Regge limit of QCD but with the spins s=1/4 instead of s=0. Generalizing recent 4D results of Grabner, Gromov, Korchemsky, and one of the authors to any D, we compute exactly at any coupling a four-point correlation function dominated by the simplest fishnet graphs of cylindric topology and extract from it exact dimensions of operators with chiral charge 2 and any spin together with some of their operator product expansion structure constants.


Racial differences in breast cancer stage at diagnosis in the mammography era.
We assessed racial differences in breast cancer mortality by stage at diagnosis, since mammography became available. We calculated adjusted odds of distant (versus local or regional) tumors for 143,249 White and 13,571 Black women aged 50 to 69 years, diagnosed with breast cancer between 1982 and 2007 and living in a Surveillance, Epidemiology, and End Results region. We compared linear trends in stage at diagnosis before and after 1998. Distant-stage cancer was diagnosed in 5.8% of White and 10.2% of Black participants. The Black-White disparity in distant tumors narrowed until 1998 (1998 adjusted difference = 0.65%), before increasing. Between 1982 and 1997, the proportion of distant tumors decreased for Blacks (adjusted odds ratio [AOR]/y = 0.973; 95% confidence interval [CI] = 0.960, 0.987) and Whites (AOR/y = 0.978; 95% CI = 0.973, 0.983), with no racial differences (P = .47). From 1998 to 2007, the odds of distant versus local or regional tumors increased for Blacks (AOR/y = 1.036; 95% CI = 1.013, 1.060) and Whites (AOR/y = 1.011; 95% CI = 1.002, 1.021); the rate of increase was greater for Blacks than Whites (P = .04). In the mammography era, racial disparities remain in stage at diagnosis.


Autoantigenic posttranslational modifications of proteins: does it apply to rheumatoid arthritis?
There are many posttranslational modifications of proteins of which all are homeostatically important either to carry out a particular structural or functional role or to allow efficient recycling of the amino acid constituents. An important feature of the modified proteins is the acquisition of autoantigenicity. That notion should have been recognized for years with the modifications of immunoglobulin G that constitute new targets for rheumatoid factors. Citrullination or the deimination of arginine residues in proteins creates epitopes that are targeted by rheumatoid autoantibodies with a diagnostic sensitivity and specificity of 40% to 70% and 92% to 99%, respectively. The how, when, and why of the responsible break in tolerance are largely speculative but apoptosis, multiple genetic and environmental influences are likely required. Identifying citrullinated proteins as autoantigens has resulted in new diagnostic and prognostic autoantibody markers for RA and studying the citrullination process and its nature and role in cell biology has provided new insights into its pathogenesis.


The effect of seasonal differences on prognostic factors in Turkish patients with breast cancer.
Several studies have shown that solar light affects the prognosis of breast cancer. This effect is mostly associated with vitamin D. In-vitro studies showed that vitamin D analogs change the receptor expression in breast cancer cell lines. In our study, we studied the effect of solar light on prognostic factors of breast cancer. Patients with breast cancer from two different regions of Turkey were included in the study. These regions have different seasonal features and solar light exposures. Nine hundred and eighty-six patients were from the Akdeniz University Medical Faculty of Antalya region, and 463 patients were from the Kayseri Education and Research Hospital of Kayseri region. The Antalya region has warm climate and more solar light exposure. The Kayseri region has relatively colder climate and less solar light exposure. When histological features are considered, the estrogen and progesterone receptor expressions were higher in the Kayseri group, and a significant difference was observed for the progesterone receptor (P=0.013). No significant difference was observed for the estrogen receptor but a significant trend was observed (P=0.056). No significant difference was observed in CerbB2 expression between groups. There were significant differences for histological and nuclear grade (P<0.001 and P=0.002). The ratio of histological grade 3 was higher in the Kayseri group and the ratio of nuclear grade 1 was higher in the Antalya group. Our study showed that, due to seasonal differences, solar light exposure leads to significant changes in prognostic factors for breast cancer. This result may be interpreted as the reflection of in-vitro findings in a clinical setting and may be accepted as one of the first such reports in the literature.


Microspatial distribution of trace elements in feline dental hard tissues: early life exposure to essential and toxic elements.
Trace elements play a key role in dental tissue development, as dental hard tissues accumulate both essential and toxic trace elements during mineralization. Characterization of the spatial accumulation pattern of trace elements may provide insight into exposure to toxic elements over time and to the nature of disease processes affecting the hard dental tissues. Here, we present the first report of the use of laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) to map the microspatial distribution of multiple trace elements, essential and toxic, across feline dental hard tissues. Eleven teeth were extracted from 8 cats. Nine teeth were from 7 cats diagnosed with idiopathic tooth resorption on intraoral radiographs prior to extraction. Two teeth were included from a cadaver that had no signs of tooth resorption on intraoral radiographs. The normal dental tissue was analyzed from each sample using LA-ICP-MS to map the microspatial distribution of essential and toxic trace elements across feline enamel, dentin, and cementum. Results showed a higher accumulation of barium and strontium in coronal dentin as compared to root dentin. The timing of the accumulation mirrors nursing timelines seen in teeth from human and non-human primates, consistent with barium and strontium being sourced from maternal milk. Results also showed a higher uptake of lead in the coronal dentin, suggesting this lead exposure was likely passed from mother to offspring. This work characterizes a baseline for elemental distribution in feline teeth linked to early life exposure to toxic elements such as lead and provides a framework for future studies investigating long-term environmental exposures to trace elements, essential and toxic, and their involvement in feline systemic and dental diseases.


Self-Assembly of α-Helical Polypeptides into Microscopic and Enantiomorphic Spirals.
Helical structures are ubiquitous in biological materials and often serve a structural purpose. Bioinspired helical materials can be challenging to synthesize and rarely reach the degree of hierarchy of their natural counterparts. Here we report the first example of particles synthesized by direct emulsification of polypeptides found to display spiral morphologies in the dry state. The polypeptides were α-helical homo- and copolypeptides of γ-benzyl glutamate and allylglycine. The chirality of the spirals was controlled by the chirality of the α-helices. Notably, right-handed α-helical polypeptides (rich in l residues) produced clockwise spirals, whereas left-handed α-helical polypeptides (rich in d residues) produced the enantiomorphs, i.e., counterclockwise spirals. The disruption of the α-helical conformation by the introduction of chiral defects led to less regular spirals and in some cases their suppression. A hypothesis for the transmission of helicity and chirality from a molecular to a higher hierarchical level, involving fibril bundling of coiled α-helices, is proposed.


[Air Bubble in the Left Ventricle due to Computed Tomography Guided Lung Needle Biopsy].
Computed tomography (CT) guided lung biopsy is a useful examination in diagnosing pulmonary diseases, but the complications such as pneumothorax or pulmonary hemorrhage can not be ignored. Among them, air embolization is a severe complication, although it is infrequently encountered. Forty two-year-old man admitted to our department for the examination of left lung tumor. CT guided lung biopsy was performed. After examination, the patient showed disturbance in cardiac function, which recovered in several minutes. Chest CT revealed air bubble in the left ventricle. After 2-hours head down position followed by bed rest, air bubble is confirmed to be dissappeared by CT.


Influence of Attenuation Correction by Brain Perfusion SPECT/CT Using a Simulated Abnormal Bone Structure: Comparison Between Chang and CT Methods.
Brain perfusion SPECT has physical phenomena such as attenuation, scatter, and degradation of resolution that impair accuracy on data acquisition. Chang and CT methods have spread application for attenuation correction (AC) and indicate the utility of AC using a brain phantom without a bone or with a normal bone structure. However, nonuniform AC of an abnormal bone structure such as postoperative bone defect after burr-hole surgery has not yet been evaluated. Therefore, we evaluated the influence of nonuniform AC of an abnormal bone structure between the 2 AC methods. Methods: We created 5 brain phantoms simulating an abnormal bone structure such as frontal, occipital, and right temporal bone defects as well as with and without a bone, which compared the influence among 3-dimensional ordered-subset expectation maximization (OSEM) incorporating scatter, attenuation, and resolution recovery corrections, and obtained 3 reconstruction processing images: OSEM (non-AC; NAC), OSEM (Chang), and OSEM (CTAC). The average counts of the 5 brain phantoms by OSEM (NAC), OSEM (Chang), and OSEM (CTAC) were evaluated by a count profile curve and counts ratio in the region of interest. Results: The counts of OSEM (NAC) and OSEM (Chang) with a bone were approximately 7% higher than those without a bone, whereas OSEM (CTAC) had a similar count ratio. The count ratio of frontal or occipital lobes with a bone defect on both OSEM (NAC) and OSEM (Chang) was 5%-10% higher than that in frontal or occipital lobes without a bone defect; however, OSEM (CTAC) had nearly identical frontal or occipital lobes with and without a bone defect. Conclusion: We conducted a phantom study simulated with and without a bone defect to demonstrate the influence of brain counts between 2 different AC methods. Although the Chang method did not correct the influence of the bone defect due to the use of a uniform attenuation coefficient, the CTAC method correctly conducted AC regardless of the presence of a bone defect.


Effect of muscarinic antagonists on micturition pressure measured by cystometry in normal, conscious rats.
To establish an in vivo model to screen new muscarinic antagonists for the treatment of overactive urinary bladder and to calculate the respective ID(50) values. The conscious rat cystometry model was modified to determine a complete dose-response curve in each animal. Spontaneous micturition was induced by infusion of room-temperature saline into rat bladders at a constant rate of 12 mL/hr. Cumulative doses of muscarinic antagonists administered in the femoral vein caused dose-dependent inhibition of the urinary bladder contraction measured as the micturition pressure. In addition, the in vitro pK(B) values for atropine, PNU-200577 (DD01), tolterodine, oxybutynin, and terodiline were determined in carbachol-contracted rat bladder strips. The rank order of the in vivo ID(50) values were atropine (14 +/- 4 nmol/kg), PNU-200577 (22 +/- 12 nmol/kg), tolterodine (94 +/- 20 nmol/kg), oxybutynin (175 +/- 89 nmol/kg), darifenacin (236 +/- 144 nmol/kg), desethyloxybutynin (313 +/- 209 nmol/kg), propiverine (4561 +/- 2079 nmol/kg), and terodiline (18,339 +/- 5348 nmol/kg). Tolterodine and PNU-200577 caused a parallel shift of the in vitro concentration-response curve to the right and did not alter the maximal contraction. The ID(50) values correlated significantly with the in vitro rat pK(B) and human bladder pA(2) values. The present results suggest that the rat cystometry model can be used in in vivo screening for new muscarinic antagonists.


Regenerable antioxidants-introduction of chalcogen substituents into tocopherols.
To improve the radical-trapping capacity of the natural antioxidants, alkylthio-, alkylseleno-, and alkyltelluro groups were introduced into all vacant aromatic positions in β-, γ- and δ-tocopherol. Reaction of the tocopherols with electrophilic chalcogen reagents generated by persulfate oxidation of dialkyl dichalcogenides provided convenient but low-yielding access to many sulfur and selenium derivatives, but failed in the case of tellurium. An approach based on lithiation of the appropriate bromo-tocopherol, insertion of chalcogen into the carbon-lithium bond, air-oxidation to a dichalcogenide, and final borohydride reduction/alkylation turned out to be generally applicable to the synthesis of all chalcogen derivatives. Whereas alkylthio- and alkylseleno analogues were generally poorer quenchers of lipid peroxyl radicals than the corresponding parents, all tellurium compounds showed a substantially improved radical-trapping activity. Introduction of alkyltelluro groups into the tocopherol scaffold also caused a dramatic increase in the regenerability of the antioxidant. In a two-phase lipid peroxidation system containing N-acetylcysteine as a water-soluble co-antioxidant the inhibition time was up to six-fold higher than that recorded for the natural antioxidants.


Antiracism in Academic Medicine: Fixing the Leak in the Pipeline of Black Physicians.
Black physicians remain severely underrepresented in academic medicine despite the documented benefits of a diverse medical faculty. Only 3.6% of academic medical faculty self-report as Black or African American. Efforts to improve faculty diversity at academic medical institutions nationwide have not made meaningful impacts. Sustained improvements in faculty diversity cannot be achieved without an actively antiracist approach, including the intentional transformation of policies, practices, and systems that persistently produce worse outcomes for Black medical students, trainees, and faculty.


D-form KLKLLLLLKLK-NH2 peptide exerts higher antimicrobial properties than its L-form counterpart via an association with bacterial cell wall components.
The antimicrobial peptide KLKLLLLLKLK-NH2 was developed based on sapesin B, and synthesized using D-amino acids. Biochemical properties of the D-form and L-form KLKLLLLLKLK-NH2 peptides were compared. In order to limit the effects due to bacterial resistance to proteolysis, antimicrobial activities of the peptides were evaluated after short-term exposure to bacteria. D-form KLKLLLLLKLK-NH2 exhibited higher antimicrobial activities than L-form KLKLLLLLKLK-NH2 against bacteria, including Staphylococcus aureus and Escherichia coli. In contrast, both the D-form and L-form of other antimicrobial peptides, including Mastoparan M and Temporin A, exhibited similar antimicrobial activities. Both the D-form KLKLLLLLKLK-NH2 and L-form KLKLLLLLKLK-NH2 peptides preferentially disrupted S. aureus-mimetic liposomes over mammalian-mimetic liposomes. Furthermore, the D-form KLKLLLLLKLK-NH2 increased the membrane permeability of S. aureus more than the L-form KLKLLLLLKLK-NH2. Thus suggesting that the enhanced antimicrobial activity of the D-form was likely due to its interaction with bacterial cell wall components. S. aureus peptidoglycan preferentially inhibited the antimicrobial activity of the D-form KLKLLLLLKLK-NH2 relative to the L-form. Furthermore, the D-form KLKLLLLLKLK-NH2 showed higher affinity for S. aureus peptidoglycan than the L-form. Taken together, these results indicate that the D-form KLKLLLLLKLK-NH2 peptide has higher antimicrobial activity than the L-form via a specific association with bacterial cell wall components, including peptidoglycan.


An iterative model for in vitro laboratory assessment of tamper deterrent formulations.
In an effort to address the continuing problem of prescription opioid abuse, manufacturers are incorporating new technologies into formulations that are designed to deter product tampering and misuse. Standards for laboratory assessment of tamper deterrent properties of new formulations have not previously been developed. Experimental designs were developed for the in vitro laboratory assessment of the tamper deterrent properties of reformulated oxycodone. Given that an exhaustive study of all potential tampering methods was impractical; this model was developed to evaluate the product in an incremental fashion with iterative changes that were amenable to objective and replicable laboratory testing. A description of the model is provided along with pertinent examples involving assessment of reformulated oxycodone with comparisons to the original formulation. Physical and chemical procedures were developed that relate to "real-world" scenarios that may be applied to opioid formulations. Test results were interpreted in relation to the relative ease or difficulty of the manipulation as compared to control materials and the amount and purity of active drug that could be accessed. Results from some of the tests were designed to be useful in predicting whether specific tampering methods would facilitate or deter drug administration by different routes of administration. This model, developed to assess the tamper deterrent properties of reformulated oxycodone, should have application in the assessment of other drug formulations designed to exhibit tamper deterrence properties.


A reversed-phase high-performance liquid chromatography method for bovine serum albumin assay in pharmaceutical dosage forms and protein/antigen delivery systems.
Bovine serum albumin (BSA) is among the most widely used proteins in protein formulations as well as in the development of novel delivery systems as a typical model for therapeutic/diagnostic proteins and the new versions of vaccines. The development of reliable and easily available assay methods for quantitation of this protein would therefore play a crucial role in these types of studies. A simple gradient reversed-phase high-performance liquid chromatography with ultra-violet detection (HPLC-UV) method has been developed for quantitation of BSA in dosage forms and protein delivery systems. The method produced linear responses throughout the wide BSA concentration range of 1 to 100 micro g/mL. The average within-run and between-run variations of the method within the linear concentration range of BSA were 2.46% and 2.20%, respectively, with accuracies of 104.49% and 104.58% for within-run and between-run samples, respectively. The limits of detection (LOD) and quantitation (LOQ) of the method were 0.5 and 1 microg/mL, respectively. The method showed acceptable system suitability indices, which enabled us to use it successfully during our particulate vaccine delivery research project.


Infection rates of respiratory syncytial virus in pediatric patients attending Phra Mongkutklao Hospital, Bangkok.
Respiratory syncytial virus (RSV) and other pathogens were isolated from nasopharyngeal secretions from 200 pediatric patients attending the Out Patient Department of Phra Mongkutklao Hospital with symptoms of upper respiratory tract infections. Their sera were also taken for determination of class specific immunoglobulin antibody titers. The positive isolation rates were 36% for RSV, 5.5% for adenovirus 1.5% for herpes simplex virus (HSV), and 4% for Staphylococcus aureus. One to 5.5% of these patients had mixed infection. Ninety five percent of patients with positive RSV isolations had IgM antibody which was found only in 30.7% in patients with negative RSV isolations. This result indicated that RSV was likely to be the most common pathogen responsible for the upper respiratory tract infections in children in Bangkok during the rainy season.


Role of Drosophila retinoblastoma protein instability element in cell growth and proliferation.
The RB tumor suppressor, a regulator of the cell cycle, apoptosis, senescence, and differentiation, is frequently mutated in human cancers. We recently described an evolutionarily conserved C-terminal "instability element" (IE) of the Drosophila Rbf1 retinoblastoma protein that regulates its turnover. Misexpression of wild-type or non-phosphorylatable forms of the Rbf1 protein leads to repression of cell cycle genes. In contrast, overexpression of a defective form of Rbf1 lacking the IE (ΔIE), a stabilized but transcriptionally less active form of the protein, induced ectopic S phase in cell culture. To determine how mutations in the Rbf1 IE may induce dominant effects in a developmental context, we assessed the impact of in vivo expression of mutant Rbf1 proteins on wing development. ΔIE expression resulted in overgrowth of larval wing imaginal discs and larger adult wings containing larger cells. In contrast, a point mutation in a conserved lysine of the IE (K774A) generated severely disrupted, reduced wings. These contrasting effects appear to correlate with control of apoptosis; expression of the pro-apoptotic reaper gene and DNA fragmentation measured by acridine orange stain increased in flies expressing the K774A isoform and was suppressed by expression of Rbf1ΔIE. Intriguingly, cancer associated mutations affecting RB homologs p130 and p107 may similarly induce dominant phenotypes.


Modeling capillary formation in calcium and copper alginate gels.
Alginate solutions in the presence of bivalent ions can form ionic cross-linked gels. In particular gelation conditions the gel structure can be characterized by great anisotropy with the presence of straight capillaries along a preferential direction. These materials can find applications mainly in high-tech sectors, like tissue engineering, where the gel characteristics play a crucial role. Despite the need of mastering the capillary formation and properties, the process remains a poorly known problem, and its development is left to trial and error procedures. In this work a quantitative approach to the description of the capillary formation process has been developed. The theory proposed by Treml et al. (2003) has been implemented and extended to an alginate different from the one used in that study and two different ions (calcium and copper). Some of the model parameters have been derived through simple measurements; others have been scaled using proper scaling equations. Experiments have been performed in different gelation conditions, varying alginate and ionic solution concentrations, to highlight the effects of these parameters on the anisotropic structure and to validate the model. In all the analyses done, the model has performed nicely showing a good reliability in the prediction of gel characteristics like capillary formation, capillary length and process time.


The down syndrome biomarker initiative (DSBI) pilot: proof of concept for deep phenotyping of Alzheimer's disease biomarkers in down syndrome.
To gain further knowledge on the preclinical phase of Alzheimer's disease (AD), we sought to characterize cognitive performance, neuroimaging and plasma-based AD biomarkers in a cohort of non-demented adults with down syndrome (DS). The goal of the down syndrome biomarker Initiative (DSBI) pilot is to test feasibility of this approach for future multicenter studies. We enrolled 12 non-demented participants with DS between the ages of 30-60 years old. Participants underwent extensive cognitive testing, volumetric MRI, amyloid positron emission tomography (PET; 18F-florbetapir), fluorodeoxyglucose (FDG) PET (18F-fluorodeoxyglucose) and retinal amyloid imaging. In addition, plasma beta-amyloid (Aβ) species were measured and Apolipoprotein E (ApoE) genotyping was performed. Results from our multimodal analysis suggest greater hippocampal atrophy with amyloid load. Additionally, we identified an inverse relationship between amyloid load and regional glucose metabolism. Cognitive and functional measures did not correlate with amyloid load in DS but did correlate with regional FDG PET measures. Biomarkers of AD can be readily studied in adults with DS as in other preclinical AD populations. Importantly, all subjects in this feasibility study were able to complete all test procedures. The data indicate that a large, multicenter longitudinal study is feasible to better understand the trajectories of AD biomarkers in this enriched population. This trial is registered with ClinicalTrials.gov, number NCT02141971.


[Peritoneal cytology in the follow-up control of malignant ovarian tumors].
From 1976 to 1982 we practised 247 transvaginal punctures with peritoneal lavage with the aim of cytological follow-up of ovarian malignomas. Those who were submitted to this treatment were 73 women with ovarian carcinoma of stage I to III, in whom after operation, antineoplastic chemotherapy and possibly radiotherapy no tumor was no longer detectable clinically. In case of positive cytology puncture was repeated in intervals of three months, in case of negative findings of 6 to 8 months. 31.6 per cent of all puncture smears were cytologically positive and 53.8 per cent certainly negative. In 14.6 per cent of all cases no well defined statement could be allotted. We can recommend peritoneal lavage for monitoring of efficiency of therapy of ovarian carcinomas on account of its high evidence and trifling annoyance.


The influence of membrane components on regulation of alternative pathway activation by decay-accelerating factor.
Decay-accelerating factor (DAF) is a C regulatory protein which functions in membranes to inhibit autologous C activation on cell surfaces. A liposome model was used to study the mechanism of DAF action and examine the effects of membrane-bound glycophorin and LPS on the regulatory activity of DAF. Liposomes were incubated in MgEGTA-treated human serum and activation of the alternative pathway measured by C3b binding. Liposomes composed of phosphatidylcholine, phosphatidylethanolamine, and cholesterol activated the alternative pathway in proportion to their content of PE. Incorporation of 10(-7) mol/mol phospholipid of either human E or HeLa cell-derived DAF inhibited C activation by liposomes containing 40% phosphatidylethanolamine by 50%, an efficiency comparable to that observed in intact E. HeLa DAF that had been treated with phosphatidylinositol-specific phospholipase C to remove its glycolipid anchor had no effect on C activation by liposomes at concentrations as high as 10(-5) mol/mol phospholipid. Incorporation of DAF into liposomes prepared with bound C3b inhibited the deposition of additional C3b by C3bBbP. However, the incorporated DAF increased the amount of Bb generated from B in the presence of D indicating that accelerated decay of the convertase was the primary effect of DAF. Similarly, treatment of intact human E with anti-DAF decreased the amount of Bb generated by the alternative pathway convertase. To study the effects of other membrane components on DAF activity, liposomes were prepared with purified human glycophorin A or LPS. In glycophorin liposomes the presence of PE was required to activate the alternative pathway and DAF inhibited this activation. In contrast, LPS liposomes bound C3b independently of PE and the incorporation of DAF had no effect. These results demonstrate that within a membrane, DAF's inhibitory activity on the alternative pathway C3 convertase is mediated independently of other membrane proteins, that in this model the major activity of DAF is to accelerate convertase decay, and that the presence of other membrane molecules that may serve as C3 acceptors can circumvent DAF function.


Status of malaria vectors in Italy.
About 30 yr after malaria eradication, surveys to assess the presence and abundance of anopheline vectors were carried out in central and southern Italy and in the islands of Sardinia and Sicily from 1992 to 1994. Anopheles labranchiae Falleroni was present in scattered foci in all regions, except for Tuscany, where it breeds almost exclusively in rice fields (Grosseto Province). Most common breeding sites were rivers and streams, followed by ponds and ground pools. The highest adult density was found in Tuscany near rice fields and along the west coast of Calabria. Anophelines in Grosseto were abundant at human bait, with peaks of > 200 landings per human per night and vectorial capacity between 7.3 and 26 for Plasmodium falciparum and between 8.3 and 32.5 for Plasmodium vivax. Anopheles sacharovi Favre, a former malaria vector in Puglia and Sardinia, was not found in these regions. The other vector in southern Italy, Anopheles superpictus Grassi, was found at low densities on the western and eastern coasts of Calabria. All anopheline populations were fully susceptible to deltamethrin, malathion, and DDT but showed reduced susceptibility to permethrin and propoxur. These data are discussed in the light of a possible reintroduction of malaria into Italy.