Performance of adenosine deaminase in detecting paediatric pleural tuberculosis: a systematic review and meta-analysis.
Paediatric pleural tuberculosis (TB) is a paucibacillary disease, which increases the difficulty of examination. We aimed to assess the performance of pleural fluid adenosine deaminase (ADA) in the detection of paediatric pleural TB. PubMed, Web of Science Core Collection, Embase and Cochrane Library databases were searched up to 20 December 2021. We used the bivariate and hierarchical summary receiver operating characteristic models to compute pooled estimates for the overall diagnostic accuracy parameters of ADA for diagnosing paediatric pleural TB. Eight studies, including 290 pleural fluid samples, met the inclusion criteria. The pooled sensitivity of ADA was 0.85 (95% CI: 0.78-0.90, I2: 55.63% < 75%) for detecting patients with paediatric pleural TB. A total of 262 pleural fluid samples from four studies were included to differentiate patients with paediatric pleural TB from controls. At a unified cut-off value of 40 U/L, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and area under the summary receiver operating characteristic curve of ADA were 0.89, 0.58, 2.09, 0.20, 10.48 and 0.89, respectively. At a cut-off value of 40 U/L, the overall performance of ADA was good for detecting paediatric pleural TB, with relatively high sensitivity and low specificity. Key messageAccurate identification of paediatric pleural TB will help eliminate TB in children. At a cut-off value of 40 U/L, the overall performance of ADA was good for detecting paediatric pleural TB, with relatively high sensitivity and low specificity.


Epidemiological aspects of acquired immunodeficiency syndrome in older Brazilians: a comparative approach.
To compare epidemiological aspects of young (15 to 49 years old) and older (more than 50 years old) AIDS patients. We analyzed 511,633 AIDS cases notified to the Brazilian Ministry of Health in the period of 1980-2008 looking at sex, age ranges, educational level and exposure category. Patients were divided into three age groups: under 15, from 15 to 49 and over 50 years old. Using a comparative approach, we analyzed data with regard to category of exposure, education (expressed in years of schooling), and sex ratio among younger (15-49) and older adults (over 50 years old). Time series data were log-transformed and normalized, and the temporal trend was evaluated. AIDS incidence is increasing among people over 50 years old in Brazil, with those older than 50 being responsible for 9.64 % of AIDS cases. There was no significant difference between educational level and gender (p = 0.468), but there was a significant difference in exposure category with a lower proportion of injecting drug users amongst the older group. Based on this analysis over the last 10 years, the percentage of AIDS cases has increased almost three times among people over 50 years old when compared with the 15-49 year-old group. Our findings suggest that public campaigns have to be specially targeted to the older segment of the population, aiming at heterosexual transmission.


Changes in electronegativity of lysosomal hydrolases during intracellular transport. An isoelectric-focusing study in subcellular fractions of rat kidney.
Isoelectric focusing was used to investigate the multiple forms of acid phosphatase, arylsulfatase, beta-glucuronidase, beta-galactosidase and beta-N-acetylhexosaminidase in the following, previously characterized subcellular fractions from rat kidney: a special rough microsomal fraction, enriched up to 9-fold over the homogenate in acid hydrolases; a smooth microsomal fraction; a Golgi membrane fraction enriched about 2.5-fold in acid hydrolases and 10- to 20-fold in several glycosyl transferases; and a lysosomal fraction enriched up to 25-fold in acid hydrolases. The electro-focusing behavior of the hydrolases in these fractions was markedly sensitive to the autolytic changes that occur under acidic conditions, even at 4 degrees C. Autolysis was minimized by extracting fractions in an alkaline medium (0.2% Triton X-100, 0.1 M sodium glycinate buffer, pH 10, 0.1 % p-nitrophenyloxamic acid) and adding p-nitrophenyloxamic acid (0.1 %), AN INHIBITOR OF LYSOSOMAL NEURAMINIDASE AND cathepsin D, to the pH gradient. The enzymes in the lysosomal fraction displayed a characteristic bimodal or trimodal distribution. Arylsulfatase, beta-glucuronidase and beta-N-acetylhexosaminidase occurred in an acidic form with an isoelectric point of 4.4, and a basic form with an isoelectric point of 6.2, 6.7 and 8.0, respectively. Acid phosphatase and beta-galactosidase occurred in an acidic, intermediate and basic form with isoelectric points of about 4. 1, 5.6 and 7.4, respectively. In the special rough microsomal fraction these enzymes were mostly in a basic form with isoelectric points between 7.5 and 9; these were 1-2 units higher than the corresponding basic forms in the lysosomal fraction. Treatment of extracts of the rough microsomal fraction with bacterial neuraminidase raised the isoelectric points of all five hydrolases by 1-2.5 units, indicating the presence of some N-acetylneuraminic acid residues in these basic glycoenzymes. The hydrolases in the Golgi fraction were largely in an acidic form with isoelectric points similar to or lower than those of the corresponding acidic components in the lysosomal fraction. The hydrolases in the smooth microsomal fraction showed isoelectric-focusing patterns intermediate between those in the rough microsomal and the Golgi fractions. These findings support the following scheme for the synthesis, transport and packaging of the lysosomal enzymes. Each hydrolase is synthesized in a restricted portion of the r


Adrenal steroid metabolites and bone status in patients with adrenal incidentalomas and hypercortisolism.
Autonomous cortisol secretion (ACS), resulting from cortisol-producing adenomas (CPA), causes endogenous steroid-induced osteoporosis (SIOP). However, the risk of endogenous SIOP cannot be explained by cortisol excess alone, and how other steroid metabolites affect bone status is unclear. ACS was diagnosed as serum cortisol ≥1.8 μg/dL after the 1-mg dexamethasone suppression test (DST-cortisol). Using liquid chromatography tandem mass spectrometry, 21 plasma steroid metabolites were measured in 73 patients with ACS and 85 patients with non-functioning adrenal tumors (NFAT). Expression of steroidogenic enzymes and relevant steroid metabolites were analyzed in some of CPA tissues. Discriminant and principal component analyses distinguished steroid profiles between the ACS and NFAT groups in premenopausal women. Premenopausal women with ACS exhibited higher levels of a mineralocorticoid metabolite, 11-deoxycorticosterone (11-DOC), and lower levels of androgen metabolites, dehydroepiandrosterone-sulfate, and androsterone-glucuronide. In premenopausal women with ACS, DST-cortisol negatively correlated with trabecular bone score (TBS). Additionally, 11-DOC negatively correlated with lumbar spine-bone mineral density, whereas androsterone-glucuronide positively correlated with TBS. The CPA tissues showed increased 11-DOC levels with increased expression of CYP21A2, essential for 11-DOC synthesis. Adrenal non-tumor tissues were atrophied with reduced expression of CYB5A, required for androgen synthesis. This study demonstrates that unbalanced production of adrenal steroid metabolites, derived from both adrenal tumor and non-tumor tissues, contributes to the pathogenesis of endogenous SIOP in premenopausal women with ACS. JSPS KAKENHI, Secom Science and Technology Foundation, Takeda Science Foundation, Japan Foundation for Applied Enzymology, AMED-CREST, JSTA-STEP, JST-Moonshot, and Ono Medical Research Foundation.


Interventions to reduce waste and improve billing compliance with medications in single-dose vials.
The purpose of this process improvement project was to implement features in the electronic health record to help reduce inappropriate drug waste and Medicare billing noncompliance for injectable drugs in single-dose vials in outpatient settings. The pharmacy department mapped processes from order entry to dose administration and claims processing. They used the process map to identify gaps that could lead to inappropriate drug waste. The organization then chose 3 drugs they believed to be at high risk of excess waste and possible billing noncompliance after cross-referencing drug cost, volume of use, and previous Medicare audits in outpatient settings. They tested a grouper and dose rounding on these drugs and compared 3 months of claims before and after implementation to assess the impact on waste and billing compliance. This study evaluated 826 claims before implementation and 1,075 claims after implementation. A total of 455 of 826 (55.1%) preimplementation claims included drug waste compared to 224 of 1,075 (20.8%) postimplementation claims. Twenty-three claims before implementation included an amount of waste exceeding the smallest vial size, putting the institution at risk of billing noncompliance. No claims had excess waste in the postimplementation period. The approximate cost of total drug waste before implementation was $1,397,437, with approximately $23,730 from inappropriate carfilzomib claims. The approximate cost of waste after implementation was $569,041. This equated to a reduction in drug waste of approximately $828,396 for bevacizumab-bvzr, carfilzomib, and ipilimumab. Using a grouper and implementing dose rounding, the institution reduced drug waste, saved money, and reduced the incidence of claims noncompliant with Medicare Part B billing requirements.


Late results in patients with Schatzki ring treated by endoscopic electrosurgical incision of the ring.
In 17 ambulatory patients with severe intermittent dysphagia an endoscopic electrosurgical radial incision of a Schatzki ring was made with a modified straight retractable sphincterotome. The incision was successfully accomplished with immediate relief of dysphagia in all patients. Fourteen patients remain asymptomatic with a mean follow-up of 46 months after the first treatment. Three patients required a second incision and they have been asymptomatic for more than 24 months. There was one mild bleeding episode. Endoscopic electrosurgical incision of the Schatzki ring is an effective therapeutic modality in selected patients.


Exercise testing in children with pulmonary valvar stenosis.
Pulmonary valvar stenosis with intact ventricular septum is a common anomaly. This lesion poses a fixed obstruction to the right ventricular outflow. The right ventricle ejects the entire cardiac output across the stenotic valve. Right ventricular systolic pressure and oxygen demand are increased at rest and more so with exercise. Exercise tolerance in children and adults with mild valvar pulmonary stenosis is nearly normal, but is diminished in those with moderate and severe stenosis, indicating impaired ability to sustain adequate cardiac output. Following relief of stenosis, cardiac performance improves in children, but remains abnormal in adults. This appears to be related to postoperative resolution of right ventricular hypertrophy in children, whereas myocardial fibrosis may explain the lack of improvement in adults.


Gender differences in compulsive exercise facets and their associations with eating disorder symptoms.
Compulsive exercise (CE) is a core symptom of eating disorders (EDs) that is common in undergraduate men and women. Importantly, CE is a multidimensional construct, and certain facets of CE (i.e., exercise to control weight or to avoid negative affect associated with missed exercise) are more strongly associated with ED symptoms in undergraduate women than others. However, less is known about how CE facets relate to ED symptoms in men. This study examined: 1) gender differences in levels of CE facets, assessed using the Compulsive Exercise Test (CET); 2) whether specific CE facets independently relate to ED symptoms; and 3) whether gender moderates these relationships. Five hundred and ninety-one university students (58.5 % men) completed the CET and Eating Pathology Symptoms Inventory. Women reported significantly greater weight control exercise, exercise for mood improvement, lack of exercise enjoyment, body dissatisfaction, and purging than men, while men reported more muscle building than women. CE motivated by avoidance of negative emotions and performed in a rule-driven manner and weight control CE were associated with the greatest number of ED symptoms. Further, rigid exercise routines were associated with greater muscle building. Women with greater weight control CE experienced more body dissatisfaction, and women with more CE motivated by avoidance of negative emotions experienced more restriction, compared to men. Overall, specific CE facets relate to ED symptoms in men and women. Findings highlight the importance of interventions designed to target unhealthy exercise motivations and of cultivating healthy attitudes towards exercise across genders.


Efficacy of Concurrent Chemotherapy for Intermediate Risk NPC in the Intensity-Modulated Radiotherapy Era: a Propensity-Matched Analysis.
This study is to evaluate the efficacy of additional concurrent chemotherapy for intermediate risk (stage II and T3N0M0) NPC patients treated with intensity-modulated radiotherapy (IMRT).440 patients with intermediate risk NPC were studied retrospectively, including 128 patients treated with IMRT alone [radiotherapy group (RT group)] and 312 paitents treated with IMRT plus concurrent chemotherapy [chemoradiotherapy group (CRT group)]. Propensity score matching was carried out to create RT and CRT cohorts equally matched for host and tumor factor. Significantly more severe acute toxicities were observed in the CRT group than in the RT group. Multivariate analyses of 440 patients failed to demonstrate concurrent chemotherapy as an independent prognostic factor for FFS, LR-FFS, and D-FFS. Between the well-matched RT cohort and the CRT cohort, no significant difference was demonstrated in all survival endpoints (FFS: 92.8% versus 91.2%, P = 0.801; LR-FFS: 95.2% versus 94.4%, P = 0.755; D-FFS: 96.4% versus 96.3%, P = 0.803; OS: 98.2% versus 98.9%, P = 0.276). Our results demonstrated that for patients with intermediate risk NPC treated with IMRT, additional concurrent chemotherapy did not provide any significant survival benefit but significantly more severe acute toxicities. However, prospective randomized trials are warranted for the ultimate confirm of our findings.


Chemiluminescence sensor for the determination of perphenazine based on a molecular imprinted polymer.
A luminol-potassium ferricyanide-perphenazine CL reaction with high sensitivity for the determination of perphenazine was found. A perphenazine molecular imprinted polymer (MIP) was synthesized. Using the perphenazine MIP as a recognition material, a novel molecular imprinting-chemiluminescence (MI-CL) sensor for the determination of perphenazine was made based on the luminol-potassium ferricyanide-perphenazine CL reaction. The sensor displayed good selectivity and high sensitivity. The linear-response range of the sensor was 5.0 x 10(-8) - 1.0 x 10(-5) g/ml with a linear correlation coefficient of 0.9961. The detection limit was 2 x 10(-8) g/ml perphenazine and the relative standard deviation for 1.0 x 10(-6) g/ml perphenazine solution was 3.7% (n = 11). The sensor was applied to the determination of perphenazine in urine samples with satisfactory results.


Concurrent pancreatic ductal changes in alcoholic liver disease.
Alcohol is a common etiological factor in both liver disease and chronic pancreatitis, but in a single individual it does not usually produce clinically significant disease in both organs. We assessed the prevalence of pancreatic ductal changes in patients presenting with alcoholic liver disease of different stages. Forty-six patients with alcoholic liver disease were included in the present study. Liver biopsy was performed in patients with normal coagulogram. Endoscopic retrograde pancreatogram was performed in all patients and changes in chronic pancreatitis were noted. Of the 46 patients with alcoholic liver disease, 31 had cirrhosis of the liver, nine had fatty liver and two patients had alcoholic hepatitis. Twenty (43.47%) patients had features of chronic pancreatitis on endoscopic retrograde pancreatogram and these consisted of minimal pancreatitis changes in 10 patients, moderate changes in nine patients and advanced changes in one patient. There was no difference in the prevalence of pancreatitis changes in cirrhotics in comparison to non-cirrhotics. There was no correlation between the amount and length of alcohol intake and changes in pancreatitis. Pancreatic ductal changes on endoscopic retrograde pancreatogram are common in patients with alcoholic liver disease.


New compact-type latex photometric immunoassay system for hemoglobin and three acute inflammation markers: neutrophil count, C-reactive protein, and anti-streptolysin O.
A new compact-type latex photometric immunoassay system, SPOTCHEM IM SI-3510 (ARKRAY, Inc., Kyoto, Japan), which assays three kinds of inflammatory markers-neutrophil count (NPC), C-reactive protein (CRP), and anti-streptolysin O (ASO)-was evaluated. Hemoglobin (Hb), which is a good marker for anemia, can also be measured with it. NPC and CRP are measured using antibodies against neutrophilic elastase and CRP, purified streptolysin O was used for ASO determination, and Hb was measured by an azide-methemoglobin method. Whole blood, serum, and plasma specimens can be used as samples with this system. In this study, whole blood treated with dipotassium ethylenediamine tetraacetic acid was used for evaluation. Linearity and reproducibility were good for all of the items studied. Good correlations were observed between the results obtained by this system and those obtained by routine methods. Since NPC exhibited a high correlation with the routine white blood cell (WBC) counts, it was judged to be useful as a substitute for WBC counting. Since this system is small and easy to operate, and evaluation revealed reliable results, it was judged to be practical for small laboratories, and satellite testing in hospitals and physicians' office laboratories for patients suspected to have acute inflammation.


Minimal Residual Disease Detection at RNA and Leukemic Stem Cell (LSC) Levels: Comparison of RT-qPCR, d-PCR and CD26+ Stem Cell Measurements in Chronic Myeloid Leukemia (CML) Patients in Deep Molecular Response (DMR).
A Deep Molecular Response (DMR), defined as a BCR::ABL1 transcript at levels ≤ 0.01% by RT-qPCR, is the prerequisite for the successful interruption of treatment among patients with Chronic Myeloid Leukemia (CML). However, approximately 50% of patients in Treatment-Free Remission (TFR) studies had to resume therapy after their BCR::ABL1 transcript levels rose above the 0.1% threshold. To improve transcript detection sensitivity and accuracy, transcript levels can be analyzed using digital PCR (dPCR). dPCR increases BCR::ABL1 transcript detection sensitivity 10-100 fold; however, its ability to better select successful TFR patients remains unclear. Beyond the role of the immune system, relapses may be due to the presence of residual leukemic stem cells (LSCs) that are transcriptionally silent. Flow cytometry can be used to identify and quantify circulating bone marrow Ph+ LSCs CD34+/CD38- co-expressing CD26 (dipeptidylpeptidase-IV). To date, the significance of circulating Ph+ LSCs in TFR is unclear. The aim of this work is to compare and examine the values obtained using the three different methods of detecting minimal residual disease (MRD) in CML at RNA (RT-qPCR and dPCR) and LSC (flowcytometry) levels among patients in TFR or exhibiting a DMR. The twenty-seven patients enrolled received treatment with either imatinib (12), dasatinib (6), nilotinib (7), bosutinib (1), or interferon (1). Twelve patients were in TFR, while the rest exhibited a DMR. The TFR patients had stopped therapy for less than 1 year (3), <3 years (2), 6 years (6), and 17 years (1). Blood samples were collected and tested using the three methods at the same time. Both d-PCR and LSCs showed higher sensitivity than RT-qPCR, exhibiting positive results in samples that were undetectable using RT-qPCR (17/27). None of the patients tested negative with d-PCR; however, 23/27 were under the threshold of 0.468 copies/μL, corresponding to a stable DMR. The results were divided into quartiles, and the lowest quartiles defined the lowest MRD. These data were strongly correlated in 15/27 patients, corresponding to almost half of the TFR patients. Indeed, the TFR patients, some lasting up to 17 years, corresponded to the lowest detectable DMR categories. To the best of our knowledge, this is the first attempt to analyze and compare DMRs in a CML population using standard (RT-qPCR) and highly sensitive (dPCR and LSCs) methods.


αs-Casein-PE6400 mixtures: surface properties, miscibility and self-assembly.
Surface properties, miscibility and self-assembly of mixtures of a food-grade αs-casein and the triblock copolymer PE6400 (PEO13-PPO30-PEO13) were examined. The properties at the surface were determined by surface pressure measurements for a 1:1 molar mixture. Comparison of the measured with the calculated isotherms show attractive interactions at surface pressures above 9mN/m. The miscibility gaps of solutions containing 0.004-0.2mmol/l αs-casein and 0.02-0.1mol/l polymer were examined. It was found that a one-phase region exists at distinct mixing ratios and temperatures. Comparison of the cloud points of mixtures of αs-casein and PE6400 with pure αs-casein showed that the presence of the triblock copolymer enhanced the solubility of the protein. The ζ-potential of the αs-casein solution decreased by addition of PE6400 to zero. Our results thus suggest that αs-casein and PE6400 are miscible. The results of the cloud point and ζ-potential measurements were explained by formation of a mixed aggregate where the PPO chains are anchored inside the hydrophobic part of the αs-casein while the PEO chains cover the charged hydrophilic part of the αs-casein thereby leading to an increase of the cloud point and a decrease in ζ-potential. This is in agreement with the attractive interactions between αs-casein and PE6400 as observed via surface pressure measurements at the surface.


In Vitro Oxidative Crosslinking of Recombinant Barnacle Cyprid Cement Gland Proteins.
Barnacle adhesion is a focus for fouling-control technologies as well as the development of bioinspired adhesives, although the mechanisms remain very poorly understood. The barnacle cypris larva is responsible for surface colonisation. Cyprids release cement from paired glands that contain proteins, carbohydrates and lipids, although further compositional details are scant. Several genes coding for cement gland-specific proteins were identified, but only one of these showed database homology. This was a lysyl oxidase-like protein (lcp_LOX). LOX-like enzymes have been previously identified in the proteome of adult barnacle cement secretory tissue. We attempted to produce recombinant LOX in E. coli, in order to identify its role in cyprid cement polymerisation. We also produced two other cement gland proteins (lcp3_36k_3B8 and lcp2_57k_2F5). lcp2_57k_2F5 contained 56 lysine residues and constituted a plausible substrate for LOX. While significant quantities of soluble lcp3_36k_3B8 and lcp2_57k_2F5 were produced in E. coli, production of stably soluble lcp_LOX failed. A commercially sourced human LOX catalysed the crosslinking of lcp2_57k_2F5 into putative dimers and trimers, and this reaction was inhibited by lcp3_36k_3B8. Inhibition of the lcp_LOX:lcp2_57k_2F5 reaction by lcp3_36k_3B8 appeared to be substrate specific, with no inhibitory effect on the oxidation of cadaverine by LOX. The results demonstrate a possible curing mechanism for barnacle cyprid cement and, thus, provide a basis for a more complete understanding of larval adhesion for targeted control of marine biofouling and adhesives for niche applications.


Cross-clade immune responses to Gag p24 in patients infected with different HIV-1 subtypes and correlation with HLA class I and II alleles.
Individuals infected with different subtypes of HIV-1 (A, B, C, D, CRF01_AE and CRF02_AG) were analyzed for their antigen-specific immune response with respect to their HLA genetics. The p24 Gag protein was selected for analysis, since previous studies of the same cohort of patients had shown that almost 80% of these individuals responded to Gag peptides of subtypes A, B and/or C. A large number of Gag antigen-specific responses were recorded. Both previously recognized as well as new epitopes were identified, assumed to bind HLA classes I and/or II. Fifteen individuals showed class I cellular responses to T cell epitopes irrespective of the infecting virus subtype. For five individuals infected with subtypes A, B, D and CRF02_AG, new T cell epitopes are described. Responses related to the patient's class I alleles are frequent, and several new putative class II responses were found.


A novel "7 sutures and 8 knots" surgical technique in reverse shoulder arthroplasty for proximal humeral fractures: tuberosity healing improves short-term clinical results.
Complex proximal humeral fractures (cPHFs) represent an important public health concern, and reverse shoulder arthroplasty (RSA) has emerged as a feasible treatment option in the elderly with high functional demands. Recent studies have shown that tuberosity healing leads to better clinical outcomes and an improved range of motion. However, the best surgical technique for the management of the tuberosities is still a topic of debate. The purpose of this retrospective observational study is to report the radiographic and clinical outcomes of a consecutive series of patients who underwent RSA for cPHFs using a novel "7 sutures and 8 knots" technique. A consecutive series of 32 patients (33 shoulders) were treated with this technique by a single surgeon from January 2017 to September 2021. Results at a minimum follow-up of 12 months and a mean ± SD follow-up of 35.9 ± 16.2 (range 12-64) months are reported. The tuberosity union rate was 87.9% (29 out of 33 shoulders), the mean Constant score was 66.7 ± 20.5 (range 29-100) points, and the mean DASH score was 33.4 ± 22.6 (range 2-85) points. The "7 sutures and 8 knots" technique, which relies on three sutures around the implant and five bridging sutures between the tuberosities, is a relatively simple procedure which provides a reliable means for anatomic restoration of the tuberosities and allows functional recovery of the shoulder in elderly patients with cPHFs treated with RSA. IV; retrospective atudy. At our institution, no institutional review board nor ethical committee approval is necessary for retrospective studies.


Microbial community changes induced by a newly isolated salt-tolerant Tetragenococcus muriaticus improve the volatile flavor formation in low-salt fish sauce.
Application of low-salt fish sauce is restricted by its easy spoilage and poor flavor formation. In this study, a salt-tolerant strain Tetragenococcus muriaticus with powerful salt tolerance was isolated as starter for the low-salt fish sauce fermentation. The 16S rRNA gene high-throughput sequencing showed that Staphylococcus was the main microbial genus at the beginning of fermentation, reaching 73.75%, followed by Tetragenococcus (16.36%) and Pseudomonas (6.68%), while Tetragenococcus quickly took over the dominant position with the relative abundance over 56.9% after 10 d fermentation and peaked at the end of fermentation. There were a total of 144 volatile compounds identified by HS-SPME-GC-MS, among which aldehydes, esters, alcohols, heterocycles, ketones, and acids were the main volatile flavor compounds and were mainly produced by Tetragenococcus, Synechococcus, Rhodococcus, Stenotrophomonas, Achromobacter, and Brucella based on the correlation network maps constructed by the Pearson's correlation coefficient after O2PLS evaluation. The Sobs, ACE, Chao, and Shannon indexes of microbial community were significantly reduced, while the Simpson index was markedly enhanced in the low-salt fish sauce fermented with T. muriaticus compared with them in the fish sauce without starter addition. The addition of T. muriaticus also obviously improved the types and concentrations of main volatile flavor compounds in the low-salt fish sauce. The correlation network map showed that Tetragenococcus was the only genus that played a crucial role in the spoilage microorganism inhibition and volatile flavor improvement in the fish sauce. T. muriaticus can be developed as a potential microbial starter for the industrial production of low-salt fish sauce.


Risk assessment for hazardous lubricants in machining industry.
Knowing that over two-thirds of lubricant disposals return to the environment with no purification process, adequate strategies are demanded to reduce their risks. For this reason, the main focus of the present study is to describe an environment-friendly approach. In the first part, two widely used lubricants (mineral-based and vegetable-based) were introduced, and the reasons for their hazards were investigated. The composition of mineral-based lubricant was characterized by x-ray fluorescence elemental analysis. The result showed the presence of phosphorus, chlorine, and zinc dialkyl dithiophosphate in its composition that many scholars considered them to be the leading risk factor in the chemical composition of mineral-based lubricants. It has been focused on the potential risks of vegetable-based lubricants, which many researchers have identified as a safe lubricant. The Pseudomonas microbe was cultivated in the vegetable-based sample, and the result showed that although vegetable-based lubricants are compatible with humans, bacteria colony can quickly grow there without making any apparent changes that lead to harm to operators in a mysterious way. In the present work, the hypothesis of the safety of unreinforced vegetable-based lubricants has been rejected, and a new window on the environmental issues of vegetable-based lubricants has been presented. In the final, to eliminate environment-human risks and to reduce consumption of lubricant and natural resources to green manufacturing, a comprehensive study on the possibility of completely removing lubricant was performed. The results showed that the machining without lubricant could be replaced with the traditional method.


Sitting or tilt position for infant lumbar puncture does not increase ultrasound measurements of lumbar subarachnoid space width.
The objective of this study was to determine whether subarachnoid space width at the site of lumbar puncture in infants changed between 3 positions: flat lateral decubitus, 45-degree tilt, and sitting. Healthy infants younger than 4 months presenting electively to a pediatric radiology department were enrolled. Exclusion criteria included signs of dehydration, illness, or previous spine/brain surgery. Subarachnoid space width at L3-L4 was measured by ultrasound with the subject placed in 3 randomly ordered positions: flat lateral decubitus, 45-degree tilt lateral decubitus, and sitting. The 3 positions were collectively compared using both repeated-measures analysis of variance and linear mixed models (LMMs) adjusted for potential confounders. Pairs of positions were compared using LMM adjusted for potential confounders. Fifty subjects were enrolled (15 male and 35 female patients). Patient weight was significantly correlated with subarachnoid space width (P = 0.02). There was no statistically significant difference in subarachnoid space width between the 3 positions (repeated-measures analysis of variance P = 0.32, LMM P = 0.40). Comparisons of pairs of positions were not significantly different: flat and 45 degrees P = 0.24, 45 degrees and sitting P = 0.98, and flat and sitting P = 0.23. The subarachnoid space width did not significantly change between the 3 positions. An increase in lumbar puncture success rate with sitting or tilt position could be due to other factors such as increased cerebrospinal fluid pressure, increased interspinous space widening, or improved identification of landmarks.


Thallium-201 per rectal scintigraphy improves prognostic evaluation in alcoholic liver cirrhosis of low and mid severity.
The aim of this work was to assess the contribution of thallium-201 chloride (Tl-201) per rectal scintigraphy in long term prognostic evaluation of alcoholic, cirrhotic patients. The data obtained from 170 biopsy-proven cirrhotic patients have been used in this 4-yr survival study. The severity of the liver disease was assessed by using the classic Child-Turcotte score as modified by Pugh (CTP score). In patients belonging to CTP class A and CTP class B, the Tl-201 test allowed the identification of subgroups with different survival rates. In these two classes of patients, the Tl-201 per rectal scintigraphy could be used for improving prognostic evaluation. In patients of class C on the other hand, 4-yr survival rates were very low, and the Tl-201 test did not bring significant additional prognostic information. Therefore, we suggest performing the Tl-201 test in cirrhotic patients of classes A and B as defined by the CTP score.


Cowden syndrome is a risk factor for multiple neoplasm: a case report.
Cowden's syndrome is an autosomal dominant disease with variable penetrance, involving the tumor suppressor phosphatase and tension homolog gene, located on chromosome 10q22-23, responsible for cell proliferation, migration, and cellular apoptosis. Its clinical presentation encompasses mucocutaneous lesions, which are present around 99% of the time; macrocephaly; and cognitive impairment, and it precedes the appearance of neoplasms such as thyroid carcinoma, breast cancer, among others. In addition to these malformations, arteriovenous malformations of the brain and spine, endocrine abnormalities, skeletal defects, and cardiopulmonary lesions may also be found. The relevance of the case is due to the fact that, through a certain phenotype, the patient's genotype can be inferred and thus followed up closely. The clinical case concerns a 28-year-old Caucasian and Portuguese woman with palmar pits, macrocephaly, and cognitive impairment. She was diagnosed with papillary thyroid carcinoma at 22 years of age and proposed total thyroidectomy. At age 27, a pregnancy was diagnosed with a Breast Imaging-Reporting and Data System 2-rated breast lump. After the histological verification, it was concluded that it was a high metastatic breast sarcoma, opting for palliative mastectomy. A genetic evaluation confirmed alteration in the phosphatase and tension homolog gene, confirming Cowden's syndrome. The patient died at age 29 due to neoplastic pathology. This report aims to alert to the clinical signs of this entity and the clinical supervision and follow-up of these patients. In order to prevent premature deaths and to improve patient's quality of life, genetic diseases with cancer impact should be diagnosed as early as possible.


Protective immune responses induced by in ovo immunization with recombinant adenoviruses expressing spike (S1) glycoprotein of infectious bronchitis virus fused/co-administered with granulocyte-macrophage colony stimulating factor.
Infectious bronchitis virus (IBV) causes tremendous economic losses associated with production inefficiencies and mortality in poultry industry worldwide. In the present report, the recombinant adenoviruses expressing chicken granulocyte-macrophage colony stimulating factor (GM-CSF) and S1 gene of nephropathogenic IBV were constructed and characterized. Then, the immunological efficacy and protection against homologous IBV challenge were assessed in specific pathogen free (SPF) chickens. The results showed that the chickens vaccinated in ovo with rAd-S1, rAd-GM-S1 (GM-CSF fused with S1 using glycine linkers) and rAd-GM-CSF plus rAd-S1 (co-administered) developed specific anti-IBV HI antibodies. Moreover, the fusion of the GM-CSF markedly increased spleen cell proliferation and IFN-γ production while mild increased in IL-4 production, which demonstrated the enhancement of cell-mediated immune responses. Following challenge with IBV, the chickens in the group vaccinated with rAd-S1 fused or co-administered with GM-CSF had fewer nephropathic lesions and showed 100% protection as compared to that of rAd-S1 alone which showed 70% protection. It indicated that the single dose in ovo vaccination of the GM-CSF fused or co-administered with S1 of IBV could enhance significantly the humoral, cellular immune responses and provide complete protection against nephropathogenic IBV challenge. This finding may provide basic information for effective in ovo vaccines design against IBV.


Hemodynamic effects of iloprost, a prostacyclin analog.
Iloprost is a chemically stable derivative of carbaprostacyclin. We studied its hemodynamic effects in 10 patients in an intensive care unit. Iloprost was infused intravenously for 3 days for the treatment of advanced obliterative arterial disease of the lower extremities. Clinically significant hemodynamic responses were obtained with an infusion rate of 0.5 ng/kg/min. All subjects tolerated the dose of 4 ng/kg/min, which increased heart rate an average of 11% and cardiac index an average of 26%. This infusion rate decreased mean arterial pressure by 15%, total peripheral resistance by 31%, and pulmonary vascular resistance by 34%. Mean pulmonary arterial pressure, pulmonary capillary wedge pressure, left and right ventricular stroke work indices, and rate pressure product did not change. At higher doses of up to 8 ng/kg/min, responses were augmented only slightly, but side effects such as headache, nausea, and abdominal colics became more prominent. The data show iloprost to be a potent vasodilator that reduces both pre- and afterload and presumably induces a compensatory increase in cardiac output and heart rate, but does not increase the work load or oxygen demand of the heart.


Exercise-induced changes in cardiac gene expression and its relation to spatial maze performance.
Cognitive performance is sensitive to both neural and non-neural changes induced by physical activity and inactivity. This study investigated whether access to physical activity outside a standard laboratory animal cage affected cognitive performance as measured by navigation of a spatial maze. It also examined gene expression in heart tissue for genes associated with cardiovascular function given recent reports of cognitive impairment associated with hyperlipidemia. Furthermore, we measured expression of neural-regulatory genes typically expressed in brain, but also found in cardiac tissue. Male Sprague-Dawley rats (n = 72) were separated into three groups having different access to physical activity: none outside a standard cage, twice-weekly physical activity, and every other day exercise on a running wheel. Compared with a sedentary group, spatial maze performance was enhanced in animals that had access to physical activity, either twice-weekly in a large box or every other day on a running wheel. Both the cardiovascular and neural-related genes expressed in the heart were distinguished by access to physical activity. Several genes that are associated with heart rate, cholesterol biosynthesis, blood pressure, and cell adhesion regulation, including GJA1, FDFT1, EDN1, and CD36, differed in animals based on access to physical activity. Neural-related genes expressed in cardiac tissue associated with neurite outgrowth, neuroplasticity, and neurogenesis including RTN4, HOMER2, ACTB, NCDN, KIF5B, and HMGB2, were expressed differently among the three groups. Significant shifts in ten cardiovascular and neural-related gene expressions in cardiac tissue were associated with physical activity and may have influenced learning and performance on a spatial maze.


Single center experience with patients on veno arterial ECMO due to postcardiotomy right ventricular failure.
Right ventricular (RV) failure is associated with poor outcome and increased mortality in cardiac surgery. Aim of our study was to analyze the outcome of veno arterial extracorporeal membrane oxygenation (va ECMO) therapy in patients with isolated RV failure in postcardiotomy cardiogenic shock (PCS) and to evaluate risk factors associated with 30-day-mortality. Between August 2006 until August 2016, 64 consecutive patients with va ECMO therapy due to fulminant RV failure in PCS were identified and included in this retrospective observation. Further, outcome data and a comparison of va ECMO survivors and nonsurvivors was conducted. The mean age of the patient cohort was 63 ± 14 years. Patients were treated with va ECMO for 79 ± 61 hours. Twenty-eight patients (44%) were successfully weaned off ECMO support. Overall 30-day-mortality was 88% (56/64). Hemoglobin concentration before ECMO implantation, maximum rise of muscle-brain type creatine kinase during ECMO therapy, as well as lactic acid concentration 24 hours after initiation of va ECMO therapy were predictive for 30-day mortality. ECMO therapy in RV failure due to PCS is shown to be associated with an excessive mortality. Regarding our data, va ECMO might only be an appropriate short-term mechanical assist device separating patients form cardiopulmonary bypass with an acceptable weaning rate. Particularly, in case of failed hemodynamic recovery of the right heart on va ECMO, direct RV bypass systems might function as a bailout option. Additionally, cardiac enzymes and lactic acid might provide valuable information in meeting therapy-related decisions.


Overweight in the Pacific: links between foreign dependence, global food trade, and obesity in the Federated States of Micronesia.
The Federated States of Micronesia (FSM) has received considerable attention for their alarming rates of overweight and obesity. On Kosrae, one of the four districts in the FSM, 88% of adults aged 20 or older are overweight (BMI > 25), 59% are obese (BMI > 30), and 24% are extremely obese (BMI > 35). Recent genetic studies in Kosrae have shown that obesity is a highly heritable trait, and more work is underway to identify obesity genes in humans. However, less attention has been given to potential social and developmental causes of obesity in the FSM. This paper outlines the long history of foreign rule and social change over the last 100 years, and suggests that a combination of dietary change influenced by foreigners, dependence on foreign aid, and the ease of global food trade contributed to poor diet and increased rates of obesity in Micronesia. The last section of the paper highlights the Pacific tuna trade as an example of how foreign dependence and global food trade exacerbates their obesity epidemic.


Estimation of a change point in a hazard function based on censored data.
The hazard function plays an important role in reliability or survival studies since it describes the instantaneous risk of failure of items at a time point, given that they have not failed before. In some real life applications, abrupt changes in the hazard function are observed due to overhauls, major operations or specific maintenance activities. In such situations it is of interest to detect the location where such a change occurs and estimate the size of the change. In this paper we consider the problem of estimating a single change point in a piecewise constant hazard function when the observed variables are subject to random censoring. We suggest an estimation procedure that is based on certain structural properties and on least squares ideas. A simulation study is carried out to compare the performance of this estimator with two estimators available in the literature: an estimator based on a functional of the Nelson-Aalen estimator and a maximum likelihood estimator. The proposed least squares estimator tums out to be less biased than the other two estimators, but has a larger variance. We illustrate the estimation method on some real data sets.


Molecular characterization of a duck Tembusu virus from China.
A new emerging flavivirus caused severe egg-drop in poultry and spread quickly across most duck-producing regions of China in 2010. Complete genome sequencing indicated that the virus genome is 10,989 nucleotides in length and possesses typical flavivirus genome organization, 5' untranslated region (UTR)-Cv-Ci-prM-M-E-NS1-NS2A-NS2B-NS3-NS4A-2K-NS4B-NS5-3'-UTR. The long open reading frame (ORF) encodes 3,425 amino acids (95-10,372 nt). The 94-nucleotide 5'-UTR is of intermediate size and the 617-nucleotide 3'-UTR is quite long relative to those of other flaviviruses. The polyprotein cleavage sites, potential glycosylation sites, distribution of cysteine residues, and 3'-UTR secondary structure were characterized. Phylogenetic analysis of the polyprotein sequences indicates that the HN isolate is closely related to Tembusu viruses of the Ntaya virus group.


RNA-sequencing transcriptome analysis of Avicennia marina (Forsk.) Vierh. leaf epidermis defines tissue-specific transcriptional response to salinity treatment.
Avicennia marina (Forsk.) Vierh. is a typical mangrove plant. Its epidermis contains salt glands, which can secrete excess salts onto the leaf surfaces, improving the salt tolerance of the plants. However, knowledge on the epidermis-specific transcriptional responses of A. marina to salinity treatment is lacking. Thus, physiological and transcriptomic techniques were applied to unravel the salt tolerance mechanism of A. marina. Our results showed that 400 mM NaCl significantly reduced the plant height, leaf area, leaf biomass and photosynthesis of A. marina. In addition, 1565 differentially expressed genes were identified, of which 634 and 931 were up- and down-regulated. Based on Kyoto Encyclopedia of Genes and Genomes metabolic pathway enrichment analysis, we demonstrated that decreased gene expression, especially that of OEE1, PQL2, FDX3, ATPC, GAPDH, PRK, FBP and RPE, could explain the inhibited photosynthesis caused by salt treatment. Furthermore, the ability of A. marina to cope with 400 mM NaCl treatment was dependent on appropriate hormone signalling and potential sulfur-containing metabolites, such as hydrogen sulfide and cysteine biosynthesis. Overall, the present study provides a theoretical basis for the adaption of A. marina to saline habitats and a reference for studying the salt tolerance mechanism of other mangrove plants.


Simple procedure for rapid identification of Vibrio cholerae from the aquatic environment.
Biochemical tests commonly used to screen for Vibrio cholerae in environmental samples were evaluated, and we found that a combination of alkaline peptone enrichment followed by streaking on thiosulfate citrate bile salts sucrose agar and testing for arginine dihydrolase activity and esculin hydrolysis was an effective rapid technique to screen for aquatic environmental V. cholerae. This technique provided 100% sensitivity and > or =70% specificity.


Prenatal diagnosis of low-level mosaicism for trisomy 21 by amniocentesis in a pregnancy associated with maternal uniparental disomy of chromosome 21 in the fetus and a favorable outcome.
We present perinatal molecular cytogenetic analysis of low-level mosaicism for trisomy 21 in a pregnancy with maternal uniparental disomy (UPD) of chromosome 21 in the fetus. A 39-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XX,+21[6]/46,XX[25]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed arr (21) × 2-3, (X) × 2 with about 18% gene dosage increase in chromosome 21 consistent with mosaic trisomy 21. Cordocentesis was performed at 20 weeks of gestation, and the cord blood lymphocytes had a karyotype of 47,XX,+21[3]/46,XX[72]. Prenatal ultrasound findings were unremarkable. After genetic counseling, the parents decided to continue the pregnancy. At 39 weeks of gestation, a 3,494-g phenotypically normal female baby was delivered without phenotypic features of Down syndrome. There was no dysplasia of middle phalanx of the fifth fingers of both hands. The cord blood had a karyotype of 47,XX,+21[2]/46,XX[48]. The placenta had a karyotype of 47,XX,+21[37]/46,XX[3]. The umbilical cord had a karyotype of 47,XX,+21[1]/46,XX[39]. aCGH analysis on the DNA extracted from cord blood revealed no genomic imbalance. Polymorphic DNA marker analysis on the DNAs extracted from cord blood and parental bloods revealed maternal uniparental heterodisomy 21 in the baby. Interphase fluorescence in situ hybridization analysis on buccal mucosal cells revealed trisomy 21 signals in 15/101 (14.9%) buccal cells at birth and in 1/122 (0.82%) buccal cells at age 45 days. Low-level mosaicism for trisomy 21 at amniocentesis associated with maternal UPD 21 in the fetus can have a favorable outcome.


Novel quinolone derivatives as potent antibacterials.
Several 7-(3R,4R-N,N'-dialkyl diaminopyrrolidinyl)-substituted quinolones were synthesized and evaluated for antibacterial activities. 5-Amino-7-(3R,4R-N,N'-dimethyldiamino-6,8-difluoro-1,4-dihydro-1-c yclopropyl -4-oxoquinoline-3-carboxylic acid was found to have potent antibacterial activity against gram +ve organisms.


Study of digoxin as inhibitor of the in vivo effects of acetyl glyceryl ether phosphorylcholine (AGEPC) in mice.
Acetyl glyceryl ether phosphorylcholine (AGEPC) and the cardiac glycoside digoxin were administered intravenously through the tail vein into ether-anesthetized SWR mice (two months old). The administered doses were 0.18 nmol AGEPC/g b.w. (a lethal one) and 75 or 125 ng digoxin/b.w. Digoxin ameliorates the effects of the lethal dose of AGEPC showing maximum activity when given 5 or 10 min after AGEPC administration to female and male animals respectively. Digoxin shows also a protective action towards the effects of AGEPC and maximum activity appears when it is given 10 min before AGEPC administration. In agreement with the picture of increased survival in digoxin pretreated animals, are our findings on life prolongation of mice which finally die from AGEPC, the amelioration of the expected fall in blood platelet counts after AGEPC administration as well as the improved performance of the animals in a series of physical tests.


Attenuated Rapid-Onset Vasodilation to Forearm Muscle Contraction in Black Men.
Non-Hispanic Black individuals have a blunted ability to vasodilate at rest compared with other racial groups. Limited studies have investigated blood flow responses to exercise in Black individuals. Recently, our laboratory demonstrated that Black men exhibit attenuated increases in forearm vascular conductance (FVC) during steady-state rhythmic handgrip. The mechanisms for this remain unknown. Herein, we used single muscle contractions, a modality that allows for assessment of rapid-onset vasodilation (ROV) independent of major elevations in shear stress, tissue metabolism, and systemic hemodynamics. Ten young, healthy Black and White men performed single forearm contractions at 20%, 40%, and 60% maximal voluntary contraction (MVC). In addition, cuff inflations were performed on the forearm to examine the contribution of mechanical compression to ROV. Forearm blood flow (FBF; duplex Doppler ultrasound), heart rate (ECG), and mean arterial pressure (Finometer) were continuously measured. FVC was calculated as FBF/mean arterial pressure. Baseline FVC (White men vs Black men, 0.75 ± 0.11 vs 0.80 ± 0.09 mL·min-1·mm Hg-1; P = 0.73), FBF, and MVCs (White men vs Black men, 54 ± 2 vs 54 ± 2 kg; P = 0.95) were similar between the groups. After single contractions, both groups exhibited intensity-dependent FVC and FBF increases during ROV; however, these responses were attenuated in the Black group at all intensities (e.g., 60%MVC FVC: White men vs Black men, +371% ± 37% vs +220% ± 23% baseline; P = 0.001). FVC and FBF responses to cuff inflation alone were also attenuated in Black individuals (P < 0.001). Collectively, these data indicate that Black men have an overall blunted ability to rapidly vasodilate compared with young White men.


Computational modelling of self-reported dietary carbohydrate intake on glucose concentrations in patients undergoing Roux-en-Y gastric bypass versus one-anastomosis gastric bypass.
Our aim was to investigate in a real-life setting the use of machine learning for modelling the postprandial glucose concentrations in morbidly obese patients undergoing Roux-en-Y gastric bypass (RYGB) or one-anastomosis gastric bypass (OAGB). As part of the prospective randomized open-label trial (RYSA), data from obese (BMI ≥35 kg/m2) non-diabetic adult participants were included. Glucose concentrations, measured with FreeStyle Libre, were recorded over 14 preoperative and 14 postoperative days. During these periods, 3-day food intake was self-reported. A machine learning model was applied to estimate glycaemic responses to the reported carbohydrate intakes before and after the bariatric surgeries. Altogether, 10 participants underwent RYGB and 7 participants OAGB surgeries. The glucose concentrations and carbohydrate intakes were reduced postoperatively in both groups. The relative time spent in hypoglycaemia increased regardless of the operation (RYGB, from 9.2 to 28.2%; OAGB, from 1.8 to 37.7%). Postoperatively, we observed an increase in the height of the fitted response curve and a reduction in its width, suggesting that the same amount of carbohydrates caused a larger increase in the postprandial glucose response and that the clearance of the meal-derived blood glucose was faster, with no clinically meaningful differences between the surgeries. A detailed analysis of the glycaemic responses using food diaries has previously been difficult because of the noisy meal data. The utilized machine learning model resolved this by modelling the uncertainty in meal times. Such an approach is likely also applicable in other applications involving dietary data. A marked reduction in overall glycaemia, increase in postprandial glucose response, and rapid glucose clearance from the circulation immediately after surgery are evident after both RYGB and OAGB. Whether nondiabetic individuals would benefit from monitoring the post-surgery hypoglycaemias and the potential to prevent them by dietary means should be investigated.KEY MESSAGESThe use of a novel machine learning model was applicable for combining patient-reported data and time-series data in this clinical study.Marked increase in postprandial glucose concentrations and rapid glucose clearance were observed after both Roux-en-Y gastric bypass and one-anastomosis gastric bypass surgeries.Whether nondiabetic individuals would benefit from monitoring the post-surgery hypoglycaemias and the potential to prevent them by dietary means should be investigated.


Type B lactic acidosis and insulin-resistant hyperglycemia in an adolescent following cardiac surgery.
To report the presence of type B lactic acidosis and insulin-resistant hyperglycemia following cardiopulmonary bypass in a pediatric patient. Case report. Tertiary referral children's hospital pediatric intensive care unit. Fourteen-year-old child with hyperlactatemia and hyperglycemia following cardiac surgery. We report a patient who following cardiopulmonary bypass for repair of his congenital heart disease developed type B lactic acidosis and hyperglycemia resistant to insulin therapy. Resolution of his hyperlactatemia and hyperglycemia occurred approximately 24 hrs postoperatively without apparent ill effect. Type B lactic acidosis is a phenomenon that may occur in the pediatric population in conjunction with insulin-resistant hyperglycemia. We observed that its resolution corresponded to improvement in the patient's hyperglycemia.


A quantitative microprobe analysis of elements in cortical and nuclear cells of the calf lens.
The outer cortical cells in the calf lens remain transparent under conditions that produce opacity in central nuclear cells. The nuclear cells opacify by a mechanism of cellular restructuring that is associated with a cytoplasmic phase separation while cortical cells do not opacify by this mechanism. In this study the differences in elemental composition of nuclear and cortical cells were analyzed using X-ray emission spectroscopy (XES) of tissue that was prepared for scanning electron microscopy. It was necessary to develop special methods of fixation and dehydration to prevent significant distortion of lens tissue and minimize solubilization and redistribution of elements during the histological processing of the tissue. We calibrated the microprobe for the quantitative analysis using gelatin standards which contained known concentrations of sulfur, potassium, phosphorus, chlorine, and cesium. The standard curves were used to determine proportionality constants, which related the intensity of X-ray emission to the molar concentration of each element, and to determine the minimum detectable levels of each element. An important finding is that the intensity of the X-ray emission is dependent on sample density only at low protein concentration. At the high protein concentrations that exist in lens, the intensity is not affected by sample density.(ABSTRACT TRUNCATED AT 250 WORDS)


Two philometrids (Nematoda: Philometridae) infecting the tigertooth croaker Otolithes ruber (Bloch & Schneider) (Teleostei: Sciaenidae) off Iran, including erection of a new genus.
Two philometrid nematodes (Philometridae) are described from the marine perciform fish (tigertooth croaker) Otolithes ruber (Bloch & Schneider) (Sciaenidae) from off Iran: Clavinemoides annulatus n. g., n. sp. based on female specimens from the caudal fin of fish from the Persian Gulf and Philometra otolithi Moravec & Manoharan, 2013 from subgravid and nongravid females collected from the ovary of fishes in the Sea of Oman and the Persian Gulf. The monotypic genus Clavinemoides n. g. is mainly characterised by a triangular oral aperture, a markedly large anterior oesophageal bulb, a distinctly annulated body and numerous fine elevated transverse cuticular bands. The finding of P. otolithi in Iranian waters represents a new geographical record of this parasite species. An updated key to the genera of the Philometrinae Baylis & Daubney, 1926 is provided.


Identification and SAR for a selective, nonpeptidyl thrombin inhibitor.
A novel, nonpeptidyl thrombin inhibitor, L-636,619 (1), was identified via topological similarity searching over the Merck Corporate Sample Database. X-ray crystallographic studies determined the geometry for ligand binding to the enzyme. Chemical modification of the P1 and P3 segments of the ligand resulted in enhanced potency and improvement in the chemical stability of the lead. Analog 9 proved to be the most interesting lead from this structurally novel series.


Caffeic acid protects human trophoblast HTR-8/SVneo cells from H2O2-induced oxidative stress and genotoxicity.
Caffeic acid is highlighted as one of the major phenolic compounds present in foods with known antioxidant activity. This phenolic is among commonly consumed substances in everyday diet of pregnant women. However, there is not enough information on its effects during pregnancy, especially the most vulnerable early stage. Extravillous trophoblast cells are specific cells of the placenta that come in direct contact with maternal uterine tissue. Through this study we investigated the cytoprotective effects of caffeic acid on H2O2-induced oxidative damage in first trimester extravillous trophoblast cell line HTR-8/SVneo. Investigated concentrations (1-100 μM) of caffeic acid showed neither cytotoxic nor genotoxic effects on HTR-8/SVneo cells. The treatment with caffeic acid 100 μM significantly increased the percentage of cells in G2/M phase of the cell cycle, compared to non-treated cells. Pretreatment with caffeic acid (10 and 100 μM) attenuated oxidative DNA damage significantly, reduced cytotoxicity, protein and lipid peroxidation, and restored antioxidant capacity in trophoblast cells following H2O2 exposure. This beneficial outcome is probably mediated by the augmentation of GSH and effective ROS scavenging by caffeic acid. These promising results require further investigations to reveal the additional mechanisms/pathways and confirmation through studies in vivo.


Affect management for HIV prevention with adolescents in therapeutic schools: the immediate impact of project balance.
Adolescents in therapeutic schools are at greater risk for HIV and other STIs than their peers due to earlier higher rates of sexual risk and difficulty managing strong emotions. HIV prevention programs that incorporate techniques for affect management (AM) during sexual situations may be beneficial. This paper determined the immediate impact of such an intervention, AM, compared to a standard, skills-based HIV prevention intervention and a general health promotion intervention (HP) for 377 youth, ages 13-19, in therapeutic schools in two cities. 1 month after the intervention, analyses that adjusted for the baseline scores found adolescents in AM were more likely to report condom use at last sex than those in HP (0.89 vs. 0.67, p = 0.02) and that their HIV knowledge was significantly greater. These data suggest that AM techniques might improve the impact of standard skills-based prevention programs for adolescents in therapeutic schools.


Early repolarization pattern in an ethnically diverse population: Increased risk in Hispanics.
Early repolarization (ER) pattern on ECG is associated with an increased mortality in Caucasians. This study analyzed the association between ER pattern and all-cause mortality in a population of multiple ethnicities. A total of 20 000 individuals were randomly selected and their ECGs were analyzed for ER pattern using the 2015 consensus: end-QRS notching or slurring with a J-point (Jp) ≥0.1 mV in contiguous inferior or lateral leads. Exclusion criteria were age <18, QRS duration of ≥120 ms, and acute myocardial infarction. Kaplan-Meier survival curves were used to assess crude survival, and multivariable logistic regression models were used to determine predictors of all-cause mortality. A total of 17 901 patients with a mean age of 53 met inclusion criteria. Individuals were 62% female, 14% White, 37% Black, 40% Hispanic, and 9% other. Median follow-up time was 6.4 years. ER pattern was noted in 995 (5.6%) patients. Jp ≥2 mm was noted in 282 (1.6%) patients. In those with ER pattern and Jp ≥1 mm, there was no difference in mortality when compared to individuals without Jp elevation (odds ratio [OR]: 0.962, 95% confidence of interval [CI]: 0.819-1.131). Patients with Jp ≥2 mm had a significantly increased all-cause mortality (OR: 1.333, 95% CI: 1.009-1.742). This increased mortality was also significant in Hispanic patients with Jp ≥2 mm (OR: 1.584, 95% CI: 1.003-2.502). ER pattern with Jp ≥2 mm is associated with increased mortality in a multiethnic population, apparently driven by an increased risk in Hispanics.


Loss of 3p or 11p alleles is associated with testicular cancer tumors.
Constitutional and tumor genotypes defined by polymorphic DNA markers were examined in 31 testicular cancer patients. Constitutional karyotypes were analyzed and clinical data presented. We analyzed 11 loci representing 8 chromosomes, including regions frequently deleted in other types of cancer. Loss of 3p or 11p sequences was detected in 8 of 28 heterozygotes (28%) and in 5 of 20 heterozygotes (25%). This gives a combined total loss of 40%. The other autosomal loci tested showed no loss or a loss of less than 10% of alleles. We suggest that this loss of heterozygosity for genetic material on chromosome 3p or on 11p is nonrandom and important in the development of a major subset of testicular neoplasms.


Comparability of Z-score equations of cardiac structures in hypoplastic left heart complex.
Hypoplastic left heart complex (HLHC) is characterized by a mitral valve or an aortic valve annular Z score < -2, antegrade flow in the ascending aorta, ductal dependency, coarctation or aortic arch hypoplasia, and absence of significant (sub)valvar stenosis. The Z scores of the mitral and aortic valve annuli are major determinants of HLHC. Therefore, the algorithm for Z-score calculation is essential for diagnosis. However, no single universal method of calculation is in use. In the scientific literature addressing HLHC, various Z-score calculation methods have been applied. The aim of this study was to evaluate Z scores derived from two-dimensional echocardiographic dimensions in patients with HLHC. To compare the different published methods using two-dimensional echocardiographic measures for Z-score calculation, a cohort of 18 newborns diagnosed with HLHC was retrospectively evaluated. In addition, the methods to determine body surface area in newborns were evaluated. Three Z-score calculation methods were included and compared. Using the method of Daubeney et al. to calculate Z scores in our cohort illustrated a lack of correlation beyond a Z score < 0, compared with the methods of Zilberman et al. and Pettersen et al. Z scores calculated using Zilberman et al.'s and Pettersen et al.'s methods were fairly consistent. The equations used by Pettersen et al. are based on the largest population of neonates. Although the different methods for calculating Z scores for mitral and aortic valve dimensions correspond fairly well in the normal range, Z scores < -2 diverge substantially. A useful scientific comparison of published data and outcomes of patients with HLHC remains elusive. The Z-score calculation algorithms used by Pettersen et al. appear to be the most appropriate for use in an evaluation of HLHC. Because these different methods can yield different values, reporting the method as well as the Z score is essential for an accurate diagnosis. Similarly, the method used to determine body surface area should be reported.


Complement protein levels and MBL2 polymorphisms are associated with dengue and disease severity.
The complement system may be crucial during dengue virus infection and progression to severe dengue. This study investigates the role of MBL2 genetic variants and levels of MBL in serum and complement proteins in Vietnamese dengue patients. MBL2 genotypes (- 550L/H, MBL2 codon 54), MBL2 diplotypes (XA/XO, YA/XO) and MBL2 haplotypes (LXPB, HXPA, XO) were associated with dengue in the study population. The levels of complement factors C2, C5, and C5a were higher in dengue and dengue with warning signs (DWS) patients compared to those in healthy controls, while factor D levels were decreased in dengue and DWS patients compared to the levels determined in healthy controls. C2 and C5a levels were associated with the levels of AST and ALT and with WBC counts. C9 levels were negatively correlated with ALT levels and WBC counts, and factor D levels were associated with AST and ALT levels and with platelet counts. In conclusions, MBL2 polymorphisms are associated with dengue in the Vietnamese study population. The levels of the complement proteins C2, C4b, C5, C5a, C9, factor D and factor I are modulated in dengue patients during the clinical course of dengue.


[Use of a microtiter-system for the determination of the antibiotic susceptibility of staphylococci with tetrazolium salts (author's transl)].
Antibiograms of staphylococci were determined in a microtiter-system (fig. 1) within 4 h. The reactions could be clearly demonstrated by the use of tetrazolium salts. The procedure proved to be particularly useful for quantitative studies.


Chemobiocatalytic transfromation of biomass into furfurylamine with mixed amine donor in an eco-friendly medium.
Biobased furfurylamine (FAM) is a versatile platform molecule for producing additives, pharmaceuticals, and pesticides. Recombinant E. coli HNND-AlaDH was created by co-expressing L-alanine dehydrogenase (AlaDH) and mutated Aspergillus terreus ω-transaminase (HNND), aiming to convert furfural (FUR) into FAM using inexpensive L-alanine and isopropylamine as mixed amine donors. In ChCl:FA:OA (10 wt%), pineapple peel, bagasse, barley shell, peanut shell, and corn stalk could be efficiently transformed into FUR under 170 °C for 10 min. Pineapple peel produced a high titer of FUR (183.3 mM). Additionally, the viscosity, surface tension and polarity of ChCl:FA:OA were explored. The biomass-derived FUR was fully transformed to FAM by HNND-AlaDH with amine donor (1:1:1 of L-Ala/isopropylamine/FUR mol/mol/mol) within 300 min. Accordingly, the FAM productivity was 0.58 g/(g xylan in pineapple peel). This chemobiocatalytic strategy established through the combination of chemocatalysis and biocatalysis could be applied to convert renewable biomass into valuable organic amines.


Optimizing virus inactivation methods for molecular detection techniques: Implications for viral protein and RNA measurements.
To facilitate the development of effective viral detection techniques, a positive control material is required for validating their quantitative performance. Inactivated viruses serve as viable control materials, as they can be handled without the constraints of biohazard safety facilities. However, inactivation alters the structure of viral component molecules, necessitating the selection of inactivation methods that have minimal effects on the target molecules relevant to molecular detection techniques. Only a limited number of studies have investigated inactivation methods to produce viral control materials. Therefore, the aim of this study was to investigate various virus inactivation methods and evaluate their impact on molecular detection techniques, with a specific focus on viral proteins and RNA. We evaluated the effects of ultraviolet (UV) irradiation, heat, beta-propiolactone (BPL), hydrogen peroxide (H2O2), and perchloric acid (HClO4) inactivation methods to identify the most effective technique and its optimal conditions. Enzyme-linked immunosorbent assay (ELISA) and reverse transcription-digital polymerase chain reaction (RT-dPCR) were employed as model assays to assess the effects of these treatments on protein and RNA measurements. Among the evaluated methods, UV and heat treatments demonstrated minimal interference with ELISA, while heat treatment had the least impact on RT-dPCR measurements. Consequently, our findings revealed that heat inactivation holds the potential for producing inactivated viruses that can be effectively used in molecular detection techniques targeting both viral protein and RNA.


Targeting HMGA1 contributes to immunotherapy in aggressive breast cancer while suppressing EMT.
Metastasis is an obstacle to the clinical treatment of aggressive breast cancer (BC). Studies have shown that high mobility group A1 (HMGA1) is abnormally expressed in various cancers and mediates tumor proliferation and metastasis. Here, we provided more evidence that HMGA1 mediated epithelial to mesenchymal transition (EMT) through the Wnt/β-catenin pathway in aggressive BC. More importantly, HMGA1 knockdown enhanced antitumor immunity and improved the response to immune checkpoint blockade (ICB) therapy by upregulating programmed cell death ligand 1 (PD-L1) expression. Simultaneously, we revealed a novel mechanism by which HMGA1 and PD-L1 were regulated by the PD-L1/HMGA1/Wnt/β-catenin negative feedback loop in aggressive BC. Taken together, we believe that HMGA1 can serve as a target for the dual role of anti-metastasis and enhancing immunotherapeutic responses.


[Prevention of reflux esophagitis after gastrectomy by the Hofmeister-Finsterer method].
The work generalizes results of diagnostics, prophylactics and treatment of reflux-esophagitis in 174 patients with resection of the stomach by the method of Hofmeister--Finsterer. The preventive use of antireflux operations (frontal crurorrhaphy and fundoesophagophrenorrhaphy) proved to be effective. Resection of the stomach in combination with hiatoplasty was followed by a less amount of reflux-esophagitis (from 48% to 10%) in the remote postoperative period.


Long-term parenteral nutrition and metabolic bone disease.
Home parenteral nutrition has prevented malnutrition in patients who cannot maintain adequate nutrition by enteral feedings alone. The risk of bone and mineral abnormalities in these patients is significant for several reasons. Pre-existing skeletal disease can occur from factors known to affect the population at large as well as from malnutrition, malabsorption, and corticosteroid use related to the underlying disease process. Long-term use of infused nutrients and potential toxins can further alter bone turnover. Hypercalciuria is frequently present during HPN, yet its etiology is poorly defined. Parenteral nutrition admixture concentrations of calcium, phosphorus, protein, sodium, and dextrose may all play a role. Any development of acidosis can certainly aggravate hypercalciuria, which may be an indirect marker of abnormal bone turnover. Although increased protein intake can promote the development of acidosis-induced calciuresis, infused phosphorus and acetate can help reduce calcium excretion. Parenteral nutrition contamination by aluminum can cause a spectrum of osteomalacic bone disease similar to aluminum-associated changes seen in renal failure patients. Even with recent attempts to remove aluminum from the parenteral admixture, low-turnover bone disease can still occur. At present, HPN-related bone disease is a poorly understood entity because of its multifaceted nature. Patients receiving long-term parenteral nutrition should be considered to have an increased risk for the development of metabolic bone disease. Early monitoring for and treatment of bone disease should be considered in all patients receiving HPN.


Scotopic sensitivity: relation to age, dietary patterns, and smoking status.
Although previous data suggest that rod-mediated sensitivity decreases with age, this decrease may be insignificant when only healthy individuals younger than 65 years are considered. In this study, we assess the relationship between age and scotopic sensitivity loss in subjects younger than 65 years to determine whether scotopic sensitivity losses can be detected when confounding factors are considered (including iris color, smoking status, and dietary patterns) and a large sample size is used. A total of 121 subjects (aged 20 to 63 years) were tested under dark-adapted (scotopic) conditions. Scotopic sensitivity was measured as absolute thresholds to a 2.8 degree, 550-nm test presented at 6 degrees in the temporal hemiretina. Stimuli were presented in Maxwellian view. When all the subjects were considered together, there was a slight nonsignificant trend for scotopic sensitivity to decline with age (p < 0.11). This tendency was largely driven by the older (45 to 63 years) past and never smokers and was statistically significant (p < 0.024 and p < 0.05, respectively) when those two groups were analyzed separately. Scotopic sensitivity for the younger (20 to 44 years) past, current, and never smokers did not decline with age. When all the variables were considered in a general model, dietary intake of vitamin E explained a significant amount of the variation in scotopic sensitivity (p < 0.03). No relationships were found between scotopic sensitivity and iris color. Age-related losses in scotopic sensitivity before age 65 are slow. Moreover, individual variations in scotopic sensitivity for younger subjects is minimal, even in the presence of dramatic stressors such as long-term, heavy exposure to cigarette smoke. These data suggest that measurements of scotopic sensitivity may not be good indicators of the retinal health of individuals younger than 65 years.


Intraoperative localization after stereotactic breast biopsy without a needle.
Needle localization breast biopsy (NLBB) is the standard for the removal of breast lesions after vacuum-assisted breast biopsy (VABB). Disadvantages include a miss rate of 0% to 22%, risk of vasovagal reactions, and scheduling difficulties. We hypothesized that the hematoma resulting from VABB could be used to localize the VABB site with intraoperative ultrasonography (US) for excision. Twenty patients had VABB followed by intraoperative US-guided excision. The previous VABB site in 19 patients was successfully visualized with intraoperative US and excised at surgery. One patient had successful removal of the targeted area under US guidance, but failed to show removal of the clip on initial specimen mammogram. This study demonstrates the effectiveness of US in identifying hematomas after VABB for excision. This technique, which can be performed weeks after VABB, improves patient comfort and allows easier scheduling.


Acute effects of bisphosphonates on new and traditional markers of bone resorption.
Bisphosphonates are known to be potent inhibitors of osteoclast activity and their only clinically relevant effect in the short-term is the selective inhibition of bone resorption. The purpose of this study was to compare the response to the intravenous administration of two bisphosphonates, clodronate and alendronate, of several biochemical markers of bone resorption, including tartrate-resistant acid phosphatase (TRAP) and cross-linked carboxyterminal telopeptide of collagen I (ICTP) in serum and hydroxyproline (OHP), free pyridinium cross-links (Pyr), and cross-linked N-telopeptides of collagen I (NTx) in urine. The study was carried out on 11 osteoporotic and 12 Pagetic subjects of both sexes, treated with clodronate (600 mg/day for 2 days) or alendronate (5 mg/day for 2 days), and monitored for 28 days after bisphosphonate administration. All the urinary markers of bone resorption showed a prompt decline after bisphosphonates, with maximum reductions after 7-14 days: Pyr decreased by 43% +/- 9% and 42% +/- 22% (mean +/- SD), respectively in osteoporotic and pagetic subjects, OHP by 51% +/- 14% and 51% +/- 20%, and NTx by 55% +/- 15% and 65% +/- 26%. In the osteoporotic group, the urinary markers began to increase again at 30 days, though still remaining well below the basal level, whereas in the pagetic group, the excretion of all markers remained depressed until the end of the observation period. The reduction of NTx was significantly greater than that of Pyr and OHP in pagetic patients (P < 0.05) and tended to be greater than that of Pyr in osteoporotic patients (p = 0.07).(ABSTRACT TRUNCATED AT 250 WORDS)


Facial and hearing outcomes in transmastoid nerve decompression for Bell's palsy, with preservation of the ossicular chain.
Facial nerve decompression is a salvage treatment for Bell's palsy patients for whom a poor prognosis is anticipated with standard medical treatment. The transmastoid approach is a frequently performed approach, but it remains unknown if this surgery is effective when the ossicular chain is preserved. This study aimed to determine the efficacy of facial nerve decompression using the transmastoid approach in Bell's palsy. This retrospective study included patients who had undergone transmastoid facial nerve decompression with ossicular chain preservation and patients who met the criteria for surgery, but received only medical treatment between January 2007 and May 2019, at a single centre. Attainment of House-Brackmann grade I at 12 months after onset of facial palsy. The recovery rate to House-Brackmann grade I in the decompression group in the early phase (≤18 days after onset) was higher than that of the medical treatment group, although the difference was not significant (70% vs 47%, P = .160). However, within this early surgery group, a subgroup of cases with ≥95% facial nerve degeneration demonstrated a significant improvement in recovery rate (73% vs 30%, P = .018). Among surgeries performed in the late phase (≥19 days), only a subgroup with ≥95% facial nerve degeneration was available for analysis, and the difference in recovery rate was not significant compared with medical treatment alone (26% vs 30%, P = 1.00). Post-surgical hearing evaluation demonstrated that average hearing deterioration was 1.3 dB which was non-significant, suggesting this procedure does not cause hearing loss. Transmastoid facial nerve decompression with ossicular chain preservation in the early phase after symptom-onset is an effective salvage treatment for severe Bell's palsy with ≥95% facial nerve degeneration.


Interaction between P450 eicosanoids and nitric oxide in the control of arterial tone in mice.
Epoxyeicosatrienoic acids (EETs) serve as endothelial-derived hyperpolarizing factors (EDHF), but may also affect vascular function by other mechanisms. We identified a novel interaction between EETs and endothelial NO release using soluble epoxide hydrolase (sEH) -/- and +/+ mice. EDHF responses to acetylcholine in pressurized isolated mesenteric arteries were neither affected by the sEH inhibitor, N-adamantyl-N'-dodecylurea (ADU), nor by sEH gene deletion. However, the EDHF responses were abolished by catalase and by apamin/charybdotoxin (ChTx), but not by iberiotoxin, nor by the cytochrome P450 inhibitor PPOH. All four EETs (order of potency: 8,9-EET >14,15-EET approximately 5,6-EET >11,12-EET) and all 4 dihydroxy derivatives (14,15-DHET approximately 8,9-DHET approximately 11,12-DHET >5,6-DHET) produced dose-dependent vasodilation. Endothelial removal or L-NAME blocked 8,9-EET and 14,15-DHET-dependent dilations. The effects of apamin/ChTx were minimal. 8,9-EET and 14,15-DHET induced NO production in endothelial cells. ADU (100 microg/mL in drinking water) lowered blood pressure in angiotensin II-infused hypertension, but not in L-NAME-induced hypertension. Blood pressure and EDHF responses were similar in L-NAME-treated sEH +/+ and -/- mice. Our data indicate that the EDHF response in mice is caused by hydrogen peroxide, but not by P450 eicosanoids. Moreover, P450 eicosanoids are vasodilatory, largely through their ability to activate endothelial NO synthase (eNOS) and NO release.


The potency of eriosematin E from Eriosema chinense Vogel. against enteropathogenic Escherichia coli induced diarrhoea using preclinical and molecular docking studies.
The main objective of the present study was to evaluate the potential of eriosematin E (ECM) isolated from the roots of Eriosema chinense against enteropathogenic Escherichia coli (EPEC) induced diarrhoea. ECM isolated from the bioactive chloroform fraction of E. chinense was subjected to antidiarrhoeal evaluation on rats against diarrhoea, induced by the oral suspension of EPEC. The study included evaluation of behavioral parameters for 6 h and up to 24 h of induction, followed by estimation of water content, the density of EPEC in stools and evaluation of various blood parameters. Further, the colonic and small intestinal tissues were subjected to biochemical estimations, antioxidant evaluation, determination of ion concentration, Na+/K+ -ATPase activity, pro-inflammatory cytokines assessment and histopathology. Finally, the impact of ECM on Na+/K+-ATPase was studied through molecular docking studies. Significant antidiarrhoeal potential of ECM was demonstrated at 5 and 10 mg/kg, p.o., however, ECM at 10 mg/kg, p.o. was found to be more effective, as confirmed through higher % protection, density of EPEC in stools and water content of stools. ECM also significantly increased the level of WBC, Hb, platelets and revealed restoration of altered antioxidants, pro-inflammatory cytokines (IL-1β and TNF-α) status and also reactivated the suppressed Na+/K+-ATPase activity, which was also confirmed through docking studies showing H-bonding of hydroxyl group of ECM with amino acids Asp 190, Asn 167 and Glu 169 thus, maintaining proper electrolyte balance and also prevented epithelial tissue damage. The overall effect of ECM may be attributed to the decline in the elevated level of cytokines, inhibition in nitric oxide production and reactivation of Na+/K+-ATPase activity resulting in reduced intestinal secretion.


Regulation of connexin expression by transcription factors and epigenetic mechanisms.
Gap junctions are specialized cell-cell junctions that directly link the cytoplasm of neighboring cells. They mediate the direct transfer of metabolites and ions from one cell to another. Discoveries of human genetic disorders due to mutations in gap junction protein (connexin [Cx]) genes and experimental data on connexin knockout mice provide direct evidence that gap junctional intercellular communication is essential for tissue functions and organ development, and that its dysfunction causes diseases. Connexin-related signaling also involves extracellular signaling (hemichannels) and non-channel intracellular signaling. Thus far, 21 human genes and 20 mouse genes for connexins have been identified. Each connexin shows tissue- or cell-type-specific expression, and most organs and many cell types express more than one connexin. Connexin expression can be regulated at many of the steps in the pathway from DNA to RNA to protein. In recent years, it has become clear that epigenetic processes are also essentially involved in connexin gene expression. In this review, we summarize recent knowledge on regulation of connexin expression by transcription factors and epigenetic mechanisms including histone modifications, DNA methylation, and microRNA. This article is part of a Special Issue entitled: The communicating junctions, roles and dysfunctions.


Ultimate failure of the Lévy Foraging Hypothesis: Two-scale searching strategies outperform scale-free ones even when prey are scarce and cryptic.
The "Lévy Foraging Hypothesis" promotes Lévy walk (LW) as the best strategy to forage for patchily but unpredictably located prey. This strategy mixes extensive and intensive searching phases in a mostly cue-free way through strange, scale-free kinetics. It is however less efficient than a cue-driven two-scale Composite Brownian walk (CBW) when the resources encountered are systematically detected. Nevertheless, it could be assumed that the intrinsic capacity of LW to trigger cue-free intensive searching at random locations might be advantageous when resources are not only scarcely encountered but also so cryptic that the probability to detect those encountered during movement is low. Surprisingly, this situation, which should be quite common in natural environments, has almost never been studied. Only a few studies have considered "saltatory" foragers, which are fully "blind" while moving and thus detect prey only during scanning pauses, but none of them compared the efficiency of LW vs. CBW in this context or in less extreme contexts where the detection probability during movement is not null but very low. In a study based on computer simulations, we filled the bridge between the concepts of "pure continuous" and "pure saltatory" foraging by considering that the probability to detect resources encountered while moving may range from 0 to 1. We showed that regularly stopping to scan the environment can indeed improve efficiency, but only at very low detection probabilities. Furthermore, the LW is then systematically outperformed by a mixed cue-driven/internally-driven CBW. It is thus more likely that evolution tends to favour strategies that rely on environmental feedbacks rather than on strange kinetics.


Subcutaneous terbutaline in children with chronic severe asthma.
A continuous subcutaneous infusion of terbutaline (CSIT) was used to treat 8 children with chronic severe asthma who continued to experience frequent symptoms, despite treatment with regular oral prednisolone. Five patients experienced a symptomatic improvement from CSIT, leading to a reduction in regular medication. Three patients did not experience any lasting benefit from CSIT. The most common side effects were related to the infusion site (bruising and local infection). CSIT may lead to an improvement in symptoms and a reduction in oral steroid dose in selected children with chronic severe asthma. These initial findings support the need for further controlled studies to evaluate the use of CSIT in severe childhood asthma.


Nickel release from metal tools in the German hairdressing trade-A current analysis.
Nickel is one of the most common contact allergens. Despite EU regulations concerning the maximum permissible release of nickel from metal objects, nickel release at inappropriately high levels from metal objects has been detected in various studies. To screen current nickel release from metal tools in the German hairdressing trade. Two hundred and twenty-nine metal tools from the German hairdressing trade were tested with the dimethylglyoxime (DMG) test for nickel release. Additionally, an employee survey was conducted to collect data about the metal tools. The DMG test showed that 21 of 229 metal tools (9.2%) released nickel. Nickel release was detected in 8 of 45 hair clips (17.8%), 2 of 27 tail combs (7.4%), and 11 of 17 tweezers (64.7%). It must be assumed that hairdressers in Germany have prolonged skin contact with nickel-releasing metal tools. This should prompt further testing for nickel release from metal tools, and the development of regulations to eliminate nickel-releasing metal tools in the (German) hairdressing trade.


Impact of a dosimetry review program on radiotherapy in group trials.
The impact of a quality assurance program on protocol compliance has been explored. A sample of 2258 patients, who received radiation therapy on 18 different NCI funded protocols, was selected for this study from the more than 6200 cases reviewed by the Quality Assurance Review Center (QARC) from 1974 to 1983. Analysis of this sample reveals a significant decrease in the protocol non-compliance rate as a function of QA participation time (35% down to 5%). The educational impact of the QA program is demonstrated by the drop in the protocol dose deviation rate from 11.4% (before QARC feedback) to 3.6% (after feedback, p less than .001). The corresponding drop in protocol deviations in treatment volume is from 21.5% to 10.5% (p less than .001). The effect of the "on-treatment" review process is studied; it is demonstrated that this process cuts the rate of major deviations in half. The technical discrepancies in dose are also analyzed and discussed.


Localization of trigeminal sensory innervation to the tongue and pharynx of the cat using horseradish peroxidase as tracer.
Trigeminal sensory innervation to the tongue and pharynx was investigated in the cat, using horseradish peroxidase (HRP) as a retrograde tracer. Following HRP application to the tongue, cells were labeled primarily in the posterolateral portion of the trigeminal ganglion. The pharynx was divided according to classical methodology into three regions: the epipharynx (nasopharynx), mesopharynx (oropharynx), and hypopharynx. When HRP was applied to the epipharynx and mesopharynx, HRP-labeled cells were found in the anteromedial and posterolateral portions of the trigeminal nerve, respectively. When HRP was applied to the hypopharynx, a single labeled cell was found in the trigeminal ganglion. These results indicate that trigeminal sensory nerve fibers in the cat branch to the tongue, epipharynx, and mesopharynx, but rarely to the hypopharynx.


Prospective evaluation of ultrasonography plus MIBI scintigraphy in selecting patients with primary hyperparathyroidism for unilateral neck exploration under local anaesthesia.
Unilateral neck exploration (UNE) is currently replacing conventional bilateral neck exploration with cervicotomy for the surgical treatment of primary hyperparathyroidism (PHPT). However, many concerns still exist about the indications and the effectiveness of this minimally invasive approach. Prospective evaluation of operative results in consecutive patients having indications for UNE on the basis of strict selection criteria consisting of ultrasound-MIBI agreement in adenoma localization, absence of thyroid disease, and psychological suitability for undergoing a procedure under local anesthesia. No intraoperative confirmation study was adopted. Among 149 consecutive PHPT patients, 45 (30.2%) had indications for UNE. No operative morbidity or mortality was observed. Mean operative time for the UNE procedure was 42 minutes (range 25 to 57). Conversion to general anesthesia was chosen for 5 patients (11.1%), whereas conversion to bilateral neck exploration was chosen for 3 patients (6.6%). For the UNE procedure, the success rate was as high as 91.7%. When the only factor indicated UNE, ultrasound-MIBI localization agreement had low sensibility (44.1%) and specificity (55.6%) but a high positive predictive value (91.1%). We concluded that UNE performed under local anesthesia, without intraoperative confirmation studies, could be considered a safe and effective approach to treating patients with PHPT, but we regret the low rate of patients selected for this procedure because of the low sensitivity of the imaging-inclusion criterion.


Xenon is not superior to isoflurane on cardiovascular function during experimental acute pulmonary hypertension.
Acute right ventricular afterload increase is a known perioperative challenge for the anaesthetic regime especially for patients with a compromised right ventricle. The accused negative inotropic action of volatile anaesthetics, with the exception of xenon, might be crucial for the adaptation of the right ventricle. Reversible pulmonary hypertension (mean pressure 40 mmHg) was induced by an infusion of the stable thromboxane A(2) analog U46619 in a porcine model (n = 35). The effects of 70 vol% xenon and 0.9 vol% isoflurane on biventricular function were studied by conductance catheter technique. Inflammation and myocardial injury was quantified using serum probes [tumour necrosis factor α (TNFα), interleukin 6 (IL-6), troponin] and myocardial tissue [B natriuretic peptide (BNP), TNFα, activated caspase 3] by enzyme-linked immunosorbance assays and reverse-transcription polymerase chain reaction. After wash in of xenon global haemodynamic parameters remained stable whereas isoflurane caused a systemic vasodilation. This led to a significant decrease in mean arterial pressure in the isoflurane group whereas cardiac output remained stable. Both substances did not alter the biventricular contractility nor did they induce changes in preload for both ventricles. Xenon led to an additional increase in right ventricular afterload, whereas isoflurane reduced pulmonary vascular resistance. No effects on systemic inflammatory response and myocardial injury were found, whereas higher apoptosis rate and expression of BNP and IL-6 was determined in the right ventricle. These results do not support the idea that xenon is more beneficial than isoflurane in right ventricular failure during pulmonary hypertension. Isoflurane did not compromise systolic ventricular function during acute PHT it only led to vasodilation in contrast to xenon.


Immunological properties of TtT/M-87 cell line established from murine pituitary tumor-associated macrophages.
TtT/M-87 cell is a macrophage cell line established from thyrotropic pituitary tumor tissues in mouse. In this paper, we report the immunological properties of M-87 cells as a model of tumor-associated macrophage. Contrasting with resident peritoneal macrophages, M-87 cells constitutively secreted small but significant amounts of TNF-alpha and IL-1 alpha, which were detectable in both biological assays (cytotoxic activity for L929 and co-mitogenic activity for Con A-induced T cell proliferation, respectively) and ELISA, and produced larger amounts of these cytokines upon stimulation with LPS. They expressed MHC class II molecules on their cell surface without stimulation by IFN-gamma. The accessory or antigen-presenting cell activity in antibody-producing response of spleen lymphocytes to sheep red blood cells was shown to be much higher in M-87 cells than normal peritoneal macrophages. In addition, when normal spleen lymphocytes were cultured with allogeneic tumor cells, such as EL-4 and S-180, in the presence of M-87 cells, lymphocytes reactive to stimulator cells were activated to manifest inhibitory effect on the tumor cell growth and also to manifest specific cytotoxic effect on the allogeneic tumor cells. These results show that M-87 cells derived from tumor-associated tissue are activated macrophages and that they are inhibitory to tumor cell growth and augmentative in the induction of T-cell-mediated immune responses.


Interactions between the lipophilic opioid sufentanil and clonidine in rats after spinal application.
Alpha2-adrenoceptor agonists, such as clonidine, can potentiate the analgesic properties of spinal opioids. In order to further extend this observation to highly lipophilic and potent spinally acting opioids, we tested the interactions between clonidine and sufentanil after both epidural and intrathecal administration in rats. The rats were equipped with spinal catheters. Antinociceptive testing was performed with the Tail Withdrawal Reaction test. Dose-response functions of sufentanil, clonidine and combinations of clonidine plus sufentanil were determined. These indicated that 1) sufentanil, but not clonidine alone, results in a dose-related antinociception after both the epidural and the intrathecal route of administration; 2) In combination with normally inactive doses of sufentanil, the addition of clonidine results in activity; 3) In a particular dose-range of sufentanil, there is a direct relationship between the doses of sufentanil and clonidine needed to produce antinociception; 4) Even at very high doses of clonidine, a minimal amount of sufentanil is needed to produce antinociception and 5) At the conditions tested here, the contribution of clonidine is minimal at high, intrinsic active doses of sufentanil.


Transfer of training as a function of target speed in pursuit-rotor performance.
Transfer of training along the difficulty dimension was studied in the rotary pursuit situation using a modified proactive-retroactive inhibition experimental design. Difficulty was varied by changing speed of rotation. Two speeds were used: 55 RPM and 60 RPM. Greater than 100% transfer was obtained in cases where training was given at 55 RPM and the final test was at 60 RPM. The pattern of training of 55/60/60 (slow to fast) proved superior in the final test to the pattern 60/55/60 (fast to slow) even though the amount of training at the two speeds was the same for the two conditions.