Construction of an electro-enzymatic bioreactor for the production of (R)-mandelate from benzoylformate.
Coupling both the electrocatalytic recycling of NADH and the enzymatic reduction of the substrate was used to produce (R)-mandelate from benzoylformate using benzoylformate reductase (BFR). The reduction of benzoylformate by BFR in combination with FAD-mediated electrolysis (at -0.5 V vs. Ag/AgCl) was complete in about 18 h and gave 47.5 mM (R)-mandelate from 50 mM substrate, while the process involving MV2+-mediated procedure (at -0.7 V vs. Ag/AgCl) produced 40 mM (R)-mandelate after 30 h. The overpotential for the NAD+ reduction could be decreased by about 0.2 V by substituting a toxic viologen derivative, MV2+, with a natural electron carrier, FAD. MV2+, however, decreased the productivity as BFR lost about 50% of its initial activity after 6 d in its presence.


Advancing Sowing Time and Conservation Tillage - The Climate-Resilient Approach to Enhance the Productivity and Profitability of Wheat.
Field experiments consisting of two sowing time (early and timely), two tillage options (conventional tillage and conservation tillage) and ten genotypes were conducted with the aim to maximize the wheat productivity and profitability. The early sowing (second fortnight of October) produced 16.0% higher grain yield compared to timely sowing (mid-November) in northern Indian Plains. However, no significant yield differences were observed between conventional tillage (CT) and conservation tillage (CST) practices. Among genotypes, the better yielders were PBW 723, BISA 927 and HD 2967. The interaction of sowing time and genotype had a significant (p < 0.05) effect on wheat yield. However, the interaction of genotype and tillage did not produce any significant response on wheat yield. The experiments conducted at farmer's fields also demonstrated similar performance of wheat under CT and CST systems but CST offered the savings of more than Rs. 3500 (US $ 47) along with 125 kg ha- 1 lesser CO2 emissions over CT due to reduction in fuel consumption associated with tillage and seed bed operations. At farmers field also, early sown wheat yielded 5.5% higher over wheat sown in November. The results of present studies show that early sowing of high yielding wheat genotypes under CST practice enhanced the productivity and profitability of wheat under rice-wheat cropping system along with lesser noxious impact on the environment. Amidst climate vagary and its menace on the agriculture, the adoption of climate-resilient management practices such as advancing the sowing time and conservation tillage can improve the productivity of long duration wheat cultivars in sub-tropical humid conditions besides lesser deleterious consequences on the environment.


Resection of large inferior vena caval thrombi from renal cell carcinoma with the use of circulatory arrest.
Removal of a large extension of renal cell carcinoma into the inferior vena cava can be a difficult operation. Circulatory arrest is an operative technique that recently has been used to assist in resection of tumors that extend into the vena cava above the level of the hepatic veins. At our clinic 18 patients were operated on with the intent of using circulatory arrest during radical nephrectomy and inferior vena caval thrombectomy. Of the 18 patients 13 ultimately underwent this procedure, since the remaining 5 had unresectable tumors. One patient died intraoperatively of an adverse reaction to protamine after technically successful removal of the tumor and thrombus. Resection was successful in 12 patients and 9 remained free of disease with short followup. We believe that the addition of circulatory arrest during resection of a large inferior vena caval thrombus allows for an opportunity to resect the tumor in a controlled situation that reduces the potential for sudden massive blood loss or a major vascular injury, and ultimately makes the operation safer.


Effect of lesions of the locus coeruleus complex on the circadian rhythm of plasma corticosterone in the mouse.
An apparently transient elevation of basal morning (08.00 h) plasma corticosterone levels in male mice was found 48 h after bilateral electrolytic lesions of the brainstem locus coeruleus complex but was not observed 6 weeks after lesioning.


Complex rearranged small supernumerary marker chromosomes (sSMC), three new cases; evidence for an underestimated entity?
Small supernumerary marker chromosomes (sSMC) are present ~2.6 x 106 human worldwide. sSMC are a heterogeneous group of derivative chromosomes concerning their clinical consequences as well as their chromosomal origin and shape. Besides the sSMC present in Emanuel syndrome, i.e. der(22)t(11;22)(q23;q11), only few so-called complex sSMC are reported. Here we report three new cases of unique complex sSMC. One was a de novo case with a dic(13 or 21;22) and two were maternally derived: a der(18)t(8;18) and a der(13 or 21)t(13 or 21;18). Thus, in summary, now 22 cases of unique complex sSMC are available in the literature. However, this special kind of sSMC might be under-diagnosed among sSMC-carriers. More comprehensive characterization of sSMC and approaches like reverse fluorescence in situ hybridization (FISH) or array based comparative genomic hybridization (array-CGH) might identify them to be more frequent than only ~0.9% among all sSMC.


Development of gene therapy for hematopoietic stem cells using lentiviral vectors.
Lentiviral vectors are promising tools for the development of gene therapy since they can transduce both quiescent and dividing target cells. Lentiviral vectors may be particularly promising gene delivery tools for hematopoietic stem cells since these target cells tend to be quiescent and are therefore difficult target cells for vectors that require dividing targets. Human hematopoietic stem cells that can repopulate NOD/SCID mice have been efficiently transduced using HIV-1-based lentiviral vectors and similar vectors can also transduce murine hematopoietic stem cells. HIV-1 vectors that contain strong general promoters can generate high levels of transgene expression and very high expression levels can be generated in erythroid cells in vivo using beta-globin regulatory sequences to control the expression of the transgene. Current lentiviral vectors have a similar level of biosafety as oncoretroviral vectors and can therefore theoretically be used in clinical gene therapy protocols. Future challenges include the generation of lentiviral vectors that can express more than one transgene at high levels and the generation of safe permanent packaging cells for practical use in clinical gene therapy trials.


Developmental language disorder in Chinese children: A systematic review of research from 1997 to 2022.
Developmental language disorder (DLD) is one of the most common neurodevelopmental disorders. The influences of DLD on language development have been delineated in detail in English. The same is not true for Chinese, a group of Sinitic languages with distinct typological features that may modify the profile of DLD crosslinguistically. We conducted a systematic search of English and Chinese journal databases and reviewed 59 studies on the manifestations of DLD in Chinese. Methodological quality appraisal of the literature revealed several areas of improvement to enhance transparency and replicability. A bibliometric analysis indicated a steep growth trajectory of this literature. Examination of the participant selection and diagnostic criteria revealed limitations and calls for the development of assessment tools and increased knowledge of evidenced-based diagnostic practice. Areas of deficits demonstrated by Chinese children with DLD were synthesized qualitatively and discussed in light of the literature on clinical markers of DLD in English.


"Passing loop" technique: a new modification of the piggyback technique tailored to voluminous liver grafts--case report.
The modified piggyback technique with side-to-side cavocavostomy decreases the risk of outflow obstruction compared with the standard piggyback method. However, this modification is not ideal for recipients who receive a graft that is voluminous or bears an enlarged caudate lobe. We modified the inferior vena cava (IVC) preservation technique against deleterious complications of compression by using a passing loop. A 49-year-old woman, who underwent orthotopic liver transplantation for hepatic failure, was allocated a large-size liver. In anticipation of serious caval compression due to the voluminous grafts, we kept the suprahepatic or infrahepatic donor caval cuffs open for an anastomosis. The first anastomosis was performed between suprahepatic donor IVC cuff and recipient middle-left hepatic vein common channel; the second anastomosis was a terminolateral cavocavostomy between infrahepatic donor IVC cuff and the anterior wall of the recipient's IVC. When the liver circulation was restored, the donor retrohepatic vena cava served as a passing loop for both hepatic venous outflow and infra-diaphragmatic venous return to bypass possible IVC compression. Our technique may solve a dilemna for patients receiving voluminous liver grafts.


Scale Insects (Hemiptera: Coccoidea) on Myrciaria dubia (Myrtaceae) in Brazil.
Commercial cultivation of the fruit tree Myrciaria dubia (Myrtaceae) is being developed in Brazil but phytophagous insects, including scale insects (Hemiptera: Coccoidea), can become pests in plantations. The coccids Ceroplastes jamaicensis White, Coccus viridis (Green), Parasaissetia nigra (Nietner), Pseudokermes vitreus (Cockerell) (Coccidae), and the diaspidid Pseudaonidia trilobitiformis (Green) were collected on M. dubia in the municipality of Belém and Tomé-Açu, state of Pará (PA), metropolitan and Northeast Pará mesoregions, Brazil. A key to species of Coccoidea recorded on M. dubia, based on adult females, is provided. Photographs for all scale insects reported on M. dubia are provided. Ceroplastes jamaicensis is recorded for the first time for Brazil and is herein reported for the first time associated with this host.


Cigarette smoking reduces human gastric luminal prostaglandin E2.
The effect of smoking three cigarettes on the release of prostaglandin E2 (PGE2) by the gastric mucosa was studied in seven healthy smokers. Smoking caused the expected increases in pulse rate, blood pressure, plasma glucose, and carboxyhaemoglobin. In addition, smoking resulted in a significant (p less than 0.05) reduction in the volume of pentagastrin stimulated gastric juice from 76.1 +/- 4.4 to 54.1 +/- 4.6 ml/15 min and PGE2 output from 22.8 +/- 4.9 to 12.2 +/- 3.8 ng/15 min but did not alter acid output. It is concluded that smoking reduces the amount of PGE2 in the gastric lumen and that this may explain why it is a risk factor for peptic ulcer.


How is anxiety related to math performance in young students? A longitudinal study of Grade 2 to Grade 3 children.
Both general and math-specific anxiety are related to proficiency in mathematics. However, it is not clear when math anxiety arises in young children, nor how it relates to early math performance. This study therefore investigated the early association between math anxiety and math performance in Grades 2 and 3, by accounting for general anxiety and by further inspecting the prevalent directionality of the anxiety-performance link. Results revealed that this link was significant in Grade 3, with a prevalent direction from math anxiety to performance, rather than the reverse. Longitudinal analyses also showed an indirect effect of math anxiety in Grade 2 on subsequent math performance in Grade 3. Overall, these findings highlight the importance of monitoring anxiety from the early stages of schooling in order to promote proficient academic performance.


Artifacts Affecting Musculoskeletal Magnetic Resonance Imaging: Their Origins and Solutions.
Among articles within the radiology literature, few present the manifestations of magnetic resonance imaging artifacts in a clinically oriented manner. Recognizing such artifacts is imperative given the increasing clinical use of magnetic resonance imaging and the emphasis by the American Board of Radiology on practical physics applications. The purpose of this article is to present magnetic resonance physics principles visually and conceptually in the context of common musculoskeletal radiology artifacts and their solutions, described using nonmathematical explanations.


Treatment stability of Milwaukee brace in idiopathic hyperkyphosis.
The Milwaukee brace is an efficient method for correcting hyperkyphosis before skeletal maturity. However, loss of correction in long-term follow-up is inevitable. To determine loss of correction and factors affecting the loss of correction. Retrospective study. A total of 49 corrected patients by Milwaukee brace participated minimum 2 years after treatment completion. The participants were categorized into two groups based on their roentgenograms: Group 1 (n = 36) had kyphotic curves of 45° or less and Group 2 (n = 13) had kyphotic curves of more than 45°. The mean loss of corrections for Group 1 and Group 2 were 3.80° (ranges = 0°-13°) and 12.92° (ranges = 8°-22°), respectively. Group 1 showed no significant difference between the average hyperkyphosis of the patients for the part-time and full-time treatment duration (p = 0.02). By contrast, a significant difference was observed between the average hyperkyphosis of patients in Group 2 for the part-time and full-time treatment duration (p < 0.05). Patients with kyphosis of 60° or less who can save the correction in full-time orthotic treatment in part-time treatment may have the least loss of correction over time. As the orthotic treatment is a time-consuming method that needs the close collaboration of patient and treatment team, it is possible that clinicians predict the probable result of treatment and efficiency of orthotic treatment. Thus, a clinician can abandon orthotic treatment and refer the patient for an operation.


Effects of in-feed clinoptilolite treatment on serum metabolic and antioxidative biomarkers and acute phase response in dairy cows during pregnancy and early lactation.
The objective of this study was to evaluate the effects of in-feed clinoptilolite (CPL) on serum metabolic and antioxidative biomarkers, acute phase proteins and reproductive performance in cows during pregnancy and lactation. A total of 78 Holstein-Friesian cows were randomly assigned into two groups: the treatment group, cows fed CPL (n = 38) which received 50 g of powdered CPL twice a day from day 180 before parturition to day 60 postpartum; and the control group (n = 40). Blood samples were taken on days 180, 90, 60, 30 and 10 before parturition, on day of calving and on days 5, 12, 19, 26, 33, 40 and 60 postpartum, and were analysed for metabolic biomarkers: glucose, triglycerides, total cholesterol, high density lipoprotein cholesterol, non-esterified fatty acids, beta-hydroxybutyrate (BHB), antioxidative biomarkers and acute phase proteins: paraoxonase-1 (PON1), apolipoprotein A-I, haptoglobin (Hp) and serum amyloid A (SAA). CPL supplementation increased concentration of glucose and significantly decreased (P < .05) level of BHB during puerperium. The SAA concentration in CPL-fed cows was significantly decreased (P < .05) on days 33, 40 and 60 postpartum as well as Hp concentration on days 0 and 12 postpartum. The results of this study suggest that the CPL-fed cows may have improved metabolic status due to the tendency of greater glucose levels and decreased BHB values during early lactation. In addition, acute phase response was lower (P < .05) in CPL-fed cows. Such an outcome might be attributed to the effect of dietary CPL on intensity and severity of the negative energy balance and inflammatory response in dairy cows.


High-resolution magnetic resonance imaging of the wrist: normal anatomy.
Magnetic resonance imaging (MRI) provided adequate depiction of carpal soft tissue structures in normal volunteers, as well as accurate anatomic correlation with cadaveric specimens. Using a high field strength system and surface coil techniques, the intricate anatomy of the wrist was best defined on long TR short TE images. However, from a practical view, T1 weighted images (TR 600 ms, TE 25 ms) were most useful because of short imaging times, satisfactory image quality, and the absence of motion artifacts. The coronal plane provided the clearest definition of important structures. Potential diagnostic limitations exist due to the inability of MRI to clearly delineate articular cartilage, joint capsules, and small interosseous ligaments. The presence of intra-articular fluid in both living subjects and cadaveric specimens, however, allowed for fine depiction of these structures on T2 weighted images.


Utilization of bone scan and single photon emission computed tomography on amputation planning in acute microvascular injury: Two cases.
The use of single photon emission computer tomography (SPECT/CT) in acute vascular injury is not well documented. SPECT/CT combines the anatomic detail of computer tomography with the functional vascular perfusion of photon emission to determine the viability of osseous structures and surrounding soft tissue. The superimposed imaging provides the practitioner with a reliable anatomic image of viability of a specific anatomic area following insult or injury. We present two cases, bilateral lower extremity frostbite, and symmetric peripheral gangrene in which this imaging modality provided guidance for surgical intervention with adequate predictability and results.


Integrated single-cell sequencing of 5-hydroxymethylcytosine and genomic DNA using scH&G-seq.
The asymmetric distribution of 5-hydroxymethylcytosine (5hmC) between two DNA strands of a chromosome enables endogenous reconstruction of cellular lineages at an individual-cell-division resolution. Further, when integrated with data on genomic variants to infer clonal lineages, this combinatorial information accurately reconstructs larger lineage trees. Here, we provide a detailed protocol for single-cell 5-hydroxymethylcytosine and genomic DNA sequencing (scH&G-seq) to simultaneously quantify 5hmC and genomic DNA from the same cell to reconstruct lineage trees at a single-cell-division resolution. For complete details on the use and execution of this protocol, please refer to Wangsanuwat et al., 2021.


Ultrasound assisted the preparation of 1-butoxy-4-nitrobenzene under a new multi-site phase-transfer catalyst--kinetic study.
In the present research work deals with the preparation of 1-butoxy-4-nitrobenzene was successfully carried out by 4-nitrophenol with n-butyl bromide using aqueous potassium carbonate and catalyzed by a new multi-site phase-transfer catalyst (MPTC) viz., N(1),N(4)-diethyl-N(1),N(1),N(4),N(4)-tetraisopropylbutane-1,4-diammonium dibromide, under ultrasonic (40 kHz, 300 W) assisted organic solvent condition. The pseudo first-order kinetic equation was applied to describe the overall reaction. Under ultrasound irradiation (40 kHz, 300 W) in a batch reactor, it shows that the overall reaction greatly enhanced with ultrasound irradiation than without ultrasound. The present study provides a method to synthesize nitro aromatic ethers by ultrasound assisted liquid-liquid multi-site phase-transfer catalysis condition.


Chronic medication intake in patients with stable coronary heart disease across Europe: Evidence from the daily clinical practice. Results from the ESC EORP European Survey of Cardiovascular Disease Prevention and Diabetes (EUROASPIRE IV) Registry.
As advised by the European guidelines on cardiovascular prevention, medication intake is a major component of secondary prevention. The aim of this study is to provide an in-depth overview of the medication intake in stable European coronary heart disease (CHD) patients. Analyses are based on the EUROASPIRE IV survey, including CHD patients (18 to 80 years) who were hospitalized for a coronary event. These patients were interviewed and examined 6 months to 3 years after their hospitalization. Information on cardiovascular medication intake is available for 7953 patients. About 99.2% of patients were on any kind of cardiovascular medication and 67.6% of patients were taking at least 5 different cardiovascular drugs. Overall, even when patients are taking the recommended drug combination as advised by the European guidelines - accounting for their disease profile - a large proportion of patients is still not on blood pressure, LDL-C or HbA1c target. In addition, huge variations were seen in medication dose intake across countries. Comparing the dose intake to the defined daily dose (DDD as published by the WHO) indicated a substantial deviation from the DDDs for a large proportion of patients. This study provides a unique overview of the cardiovascular medication intake in CHD patients. Overall, even when patients are taking the advised drug combination, a large proportion of patients is still not on risk factor target. Physicians should seek for a balance in medication intake and appropriate dose, accounting both for the benefits and risks of chronic drug intake.


[Attempts at inter-specific hybridization in Sphaeroma (Crustacea Isopoda Flabellifera)].
An interspecific hybridization between five tunisian species of the genus Sphaeroma has been attempted. All the trials failed whatever the crossing attempted. The lack of natural hybrids between forms living together constitutes a fundamental criterium for specific discrimination.


X-linked mental retardation, short stature, microcephaly and hypogonadism maps to Xp22.1-p21.3 in a Belgian family.
X-linked mental retardation (XLMR) is a heterogeneous disorder that can be classified as either non-specific (MRX), when mental retardation is the only feature, or as syndromic mental retardation (MRXS). Genetic defects underlying XLMR are being identified at a rapid pace, often starting from X-chromosomal aberrations and XLMR families with a well-defined linkage interval. Here, we present a new family with a syndromic form of XLMR, including mild mental retardation, short stature, microcephaly and hypogonadism. Two-point linkage analysis with 24 polymorphic markers spanning the entire X chromosome was carried out. We could assign the causative gene to a 6 cM interval in Xp22.1-p21.3, with a maximum LOD score of 2.61 for markers DXS989 and DXS1061 at theta = 0.00. No mutations were found in the presented family for two known MRX genes mapping to this interval, ARX and IL1RAPL-1. These data indicate that the interval Xp22.1-p21.3 contains at least one additional MRXS gene.


Efficacy of 1% 4-ethoxybenzaldehyde in reducing facial erythema.
Facial erythema is a common postsurgical and dermatologic problem. It is commonly the result of dermal inflammation arising from either a facial surgical procedure, such as laser resurfacing, dermabrasion, or a face peel, or from an underlying dermatologic condition, such as rosacea. Facial erythema is difficult for the dermatologist to treat in both settings because topical corticosteroids cannot be used long term on the thin facial skin and anti-inflammatory oral or topical antibiotics have associated side effects. The goal of this pilot study was to evaluate the anti-inflammatory effect of 1% 4-ethoxybenzaldehyde in a rosacea model of facial erythema. Thirty subjects with mild to moderate stable rosacea were enrolled in this 4-week, double-blind, vehicle-controlled study. Photographs, investigator assessment, and subject assessment were the efficacy criteria. There was a statistically significant reduction in facial erythema (p<.01) in those subjects who used the active for 4 weeks, as well as a statistically significant improvement in uneven skin tone (p<.01) and the overall severity of the disease (p<.01). There was no statistically significant difference in any of these three indices in the vehicle-treated group. The results suggest that benzaldehyde-derived anti-inflammatory agents may be useful in reducing facial erythema in a rosacea model.


Large Deviations for Subcritical Bootstrap Percolation on the Erdős-Rényi Graph.
We study atypical behavior in bootstrap percolation on the Erdős-Rényi random graph. Initially a set S is infected. Other vertices are infected once at least r of their neighbors become infected. Janson et al. (Ann Appl Probab 22(5):1989-2047, 2012) locates the critical size of S, above which it is likely that the infection will spread almost everywhere. Below this threshold, a central limit theorem is proved for the size of the eventually infected set. In this work, we calculate the rate function for the event that a small set S eventually infects an unexpected number of vertices, and identify the least-cost trajectory realizing such a large deviation.


Pharmacological treatment of established rheumatoid arthritis.
Rheumatoid arthritis (RA) is a chronic, inflammatory condition of unknown aetiology that affects about 1% of the general population. Although the optimal care of RA patients requires various modalities, pharmacotherapy remains the cornerstone of treatment for established RA. The current therapeutic model encourages a step-up approach that safely incorporates several currently available classes of agents: non-steroidal anti-inflammatory drugs, selective cyclo-oxygenase-2 inhibitors, glucocorticoids, disease-modifying anti-rheumatic drugs, and biological agents (tumour necrosis factor-alpha inhibitors and interleukin-1 receptor antagonist). Non-steroidal anti-inflammatory drugs, selective cyclo-oxygenase-2 inhibitors and glucocorticoids, which offer a quick onset of symptom relief, are used mainly as adjunctive therapies. Disease-modifying anti-rheumatic drugs and biologicals have been successful in altering disease outcome and slowing radiographic progression. The indications, efficacy and safety of these agents in clinical trials and practice are reviewed in this chapter.


Temporal Trends in Angina, Myocardial Perfusion, and Left Ventricular Remodeling in Women With No Obstructive Coronary Artery Disease Over 1-Year Follow-Up: Results From WISE-CVD.
Background Women with ischemia and no obstructive coronary artery disease are increasingly recognized and found to be at risk for major adverse cardiovascular events. Methods and Results In 214 women with suspected ischemia and no obstructive coronary artery disease who completed baseline and 1-year follow-up vasodilatory stress cardiac magnetic resonance imaging, we investigated temporal trends in angina (Seattle Angina Questionnaire [SAQ]), myocardial perfusion reserve index, blood pressure, and left ventricular (LV) remodeling and function from baseline to 1-year follow-up and explored associations between these different parameters. We observed concordant positive trends in 4/5 SAQ domains, SAQ-7, myocardial perfusion reserve index, blood pressure, LV mass, and LV mass-to-volume ratio. There was no association between SAQ-7 improvement and myocardial perfusion reserve index improvement over 1-year follow-up (P=0.1). Higher indexed LV end-diastolic volume and time to peak filling rate at baseline were associated with increased odds of clinically relevant SAQ-7 improvement (odds ratio [OR], 1.05; 95% CI, 1.0-1.1; and OR, 2.40; 95% CI, 1.1-5.0, respectively). Hypertension was associated with decreased odds of SAQ-7 improvement (OR, 0.41; 95% CI, 0.19-0.91). Conclusions In women with ischemia and no obstructive coronary artery disease clinically treated with cardiac medications over 1 year, we observed concurrent temporal trends toward improvement in SAQ, myocardial perfusion reserve index, blood pressure, LV mass, and LV mass-to volume ratio. We showed that abnormalities in LV morphology and diastolic function at baseline were predictive of clinically significant improvement in angina at follow-up, whereas history of hypertension was associated with lower odds. Future studies are needed to assess the mechanisms and treatments responsible for the improvements we observed. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02582021.


New strategies for energy supply of cardiac implantable devices.
Heart disease and atrial fibrillation are the leading causes of death worldwide. Patient morbidity and mortality associated with cardiovascular disease can be reduced by more accurate and continuous diagnostic and therapeutic tools provided by cardiovascular implantable electronic devices (CIEDs). Long-term operation of CIEDs continues to be a challenge due to limited battery life and the associated risk of device failure. To overcome this issue, new approaches for autonomous battery supply are being investigated. Here, the state of the art in CIED power supply is presented and an overview of current strategies for autonomous power supply in the cardiovascular field is given, using the body as a sustainable energy source. Finally, future challenges and potentials as well as advanced features for CIEDs are discussed. CIEDs need to fulfil more requirements for diagnostic and telemetric functions, which leads to higher energy requirements. Ongoing miniaturization and improved sensor technologies will help in the development of new devices.


Application of fractal analysis to neuronal dendritic arborisation patterns of the monkey dentate nucleus.
The deep nuclei of the cerebellar cortex have not yet received adequate exploratory attention. An exception is represented by the pioneering work of Chan-Palay, published in 1977, on the dentate nucleus morphology. She has classified each individual cell in the dentatus of the monkey into one of six types. Although fractal analysis is presently the most prominent quantitative method for morphometric neuronal studies, no article referring to applications of this method to the analysis of cell types of the dentate nucleus has so far been published. In the present study we apply fractal analysis to this unsolved problem and calculate the fractal dimension for each dendritic arbour of a neuron. We will hereby prove that by application of fractal analysis to the dendritic arbours of these cells whilst ignoring other neuronal attributes allows for clear discrimination of only three cell types.


Impact of anemia on major bleeding in patients taking oral anticoagulants for nonvalvular atrial fibrillation.
Anemia is encountered in patients with nonvalvular atrial fibrillation (NVAF) on oral anticoagulants (OACs) but the prognostic impact was not well scrutinized in real-world settings. We conducted a historical multicenter registry of patients with NVAF taking OACs at 71 centers in Japan. Those with mechanical heart valves or a history of pulmonary thrombosis or deep venous thrombosis were excluded. Anemic patients were divided into three groups of hemoglobin (Hb) level: moderate/severe (Hb < 11.0 g/dL), mild (men: Hb of 11.0-12.9 g/dL; women: Hb of 11.0-11.9 g/dL), and no anemia. The endpoints included major bleeding, hemorrhagic stroke, ischemic events, ischemic stroke, and all-cause mortality. Among 7558 consecutive patients (mean age, 73 years; men 67%) registered in February 2013 and followed until February 2017, 2100 (28%) patients had anemia. The anemic patients were older (moderate/severe: 79 years; mild: 77 years; no anemia: 71 years, p < .001), and HAS-BLED score was significantly higher in the anemic patients (p < .001). The cumulative incidences at 4 years of major bleeding in moderate/severe, mild, and no anemia group, were 14.9%, 10.7%, and 6.4%, respectively. The adjusted hazard ratios (HRs) (95% confidential intervals (CIs)) of major bleeding of moderate/severe and mild anemia group were 1.96 (1.49-2.58) and 1.48 (1.17-1.87) compared to no anemia group. The adjusted HRs (95% CIs) for ischemic events were 0.63 (0.39-0.99) and 1.03 (0.76-1.39). The severity of anemia in the patients with NVAF on OACs was associated with major bleeding.


High-throughput BioSorter quantification of relative mitochondrial content and membrane potential in living Caenorhabditis elegans.
Mitochondrial respiratory chain disease is caused by a wide range of individually rare genetic disorders that impair cellular energy metabolism. While fluorescence microscopy analysis of nematodes fed MitoTracker Green (MTG) and tetramethylrhodamine ethyl ester (TMRE) can reliably quantify relative mitochondrial density and membrane potential, respectively, in C. elegans models of mitochondrial dysfunction, it is a tedious process with limitations in the number and age of animals that can be studied. A novel, large particle, flow cytometry-based method reported here accelerates and automates the relative quantitation of mitochondrial physiology in nematode populations. Relative fluorescence profiles of nematode populations co-labeled with MTG and TMRE were obtained and analyzed by BioSorter (Union Biometrica). Variables tested included genetic mutation (wild-type N2 Bristol versus nuclear-encoded respiratory chain complex I mutant gas-1(fc21) worms), animal age (day 1 versus day 4 adults), classical respiratory chain inhibitor and uncoupler effects (oligomycin, FCCP), and pharmacologic therapy duration (24h versus 96h treatments with glucose or nicotinic acid). A custom MATLAB script, which can be run on any computer with MATLAB runtime, was written to automatically quantify and analyze results in large animal populations. BioSorter analysis independently validated relative MTG and TMRE changes that we had previously performed by fluorescence microscopy in a variety of experimental conditions, with notably greater animal population sizes and substantially reduced experimental time. Older, fragile animal populations that are difficult to study by microscopy approaches were readily amenable to analysis with the BioSorter method. Overall, this high-throughput method enables efficient relative quantitation of in vivo mitochondrial physiology over time in a living animal in response to gene mutations and candidate therapies, which can be used to accelerate the translation of basic research into optimization of clinical therapies for mitochondrial disease.


Limited intercellular spread of spontaneous Ca2+ signals via gap junctions between mouse chromaffin cells in situ.
Using a confocal laser-scanning microscope, we measured the changes in the cytosolic Ca(2+) concentration ([Ca]i) of chromaffin cells on adrenal slice preparations of mouse. The spontaneous fluctuations of [Ca]i were often observed in situ, as reported in isolated rat and bovine cells. Intriguingly, the spontaneous [Ca]i changes in one cell were often transmitted to one or two adjacent cells, and the synchronized [Ca]i changes were often observed in two adjacent cells, both of which failed to respond to ATP. The synchronized [Ca]i changes between two cells were much less frequently observed in rat than in mouse adrenals. The spontaneous [Ca]i changes were also synchronized between closely touching mouse chromaffin cells in culture. These results suggest that the spread of Ca(2+) signaling is mediated by low-conductance intercellular coupling.


Leptomeningeal dissemination of ovarian carcinoma through a ventriculoperitoneal shunt.
Dissemination of ovarian cancer occurs mainly within the peritoneal cavity and central nervous system involvement (CNS) is encountered rarely. This report describes an unusual case with iatrogenic leptomeningeal metastasis from ovarian carcinoma. 36 year-old lady diagnosed with ovarian carcinoma develops neurologic symptoms 10 months following primary treatment. Medical history reveals a venticuloperitoneal shunt placement 16 years ago for non-communicating hydrocephalus. She undergoes surgery for obstruction of the VP catheter and pathologic evaluation reveals metastatic carcinoma consistent with the primary diagnosis. With subsequent systemic chemotherapy, the patient remains alive for 2 years. This report describes a unique patient with ovarian cancer, who developed iatrogenic leptomeningeal involvement of the lateral ventricule through an indwelling ventriculoperitoneal shunt.


Worldwide initiatives aimed to train professionals in the use of the ICD-11.
The chapter on mental disorders of the 11th revision of the International Classification of Diseases (ICD-11) has been now finalized. Training of mental health professionals in the use of the chapter is taking place worldwide. Information is provided on the ICD-11 training courses taking place recently, including that co-organized by the Naples World Health Organization (WHO) Collaborating Centre on Research and Training in Mental Health and the European Psychiatric Association; those which will be held in the next few months, such as the one co-organized by the World Psychiatric Association and the Global Mental Health Academy, to be held online from 8 to 29 November 2021; and the training course set up by the WHO Collaborating Centre on Mental Health at the Columbia University, in collaboration with the WHO Department of Mental Health and Substance Use, which can be accessed only by the members of the WHO Global Clinical Practice Network. Psychiatrists of all countries of the world are encouraged to become familiar with the ICD-11 chapter on mental disorders, which will be adopted shortly by most countries worldwide.


Lack of familiarity with genetic testing among patients in Ireland with Cancer.
Cancer gene panel testing is available in Ireland. The need for a clear strategy to deal with patient information generated from tumour genomic testing is recognised as a challenge in the National Cancer Strategy. However, the public's attitude and opinions regarding these results is not known in Ireland. This prospective questionnaire study assessed the knowledge and opinions of patients in a national oncology centre, surrounding cancer gene panel testing. An anonymised modified validated questionnaire was completed by volunteering patients in the medical oncology department. It comprised 14 questions which assessed patient's familiarity, intention, benefits and concerns associated with tumour genetic testing using a four-point Likert scale. Patients recorded their primary cancer diagnosis and family cancer history. Eighty-four patients completed the questionnaire with 77 (92%) patients declaring their primary cancer diagnosis. The median age was 56 (range 26 to 83) years. Overall, 42% (n = 35) of oncology patients were familiar/somewhat familiar with testing and 90% (n = 76) stated they would avail of genetic testing if available. Patients with breast cancer were no more likely to avail of genetic testing when compared with the non-breast cancer cohort (n = 21 vs. 56, p = 0.58) though they identified concerns with potential discrimination. This is the first prospective Irish study to assess opinions surrounding cancer gene results. Addressing patient's lack of information as regards genetic testing is the first step in establishing a national cancer genetics testing programme in Ireland.


Rapid relief of spontaneous angina by intraventricular diltiazem: systemic and regional coronary haemodynamic determinants.
The authors describe a case of spontaneous angina during catheterization in a patient with left anterior descending and circumflex stenosis promptly relieved by diltiazem, 10 mg, given in the left ventricle. Coronary and systemic haemodynamics measured during and at the end of angina demonstrated an increase in blood flow to the ischaemic myocardium as the mechanism responsible for the diltiazem-induced angina relief.


Kinetics studies on the renal transport of probenecid in vitro.
1. The kinetic parameters of renal transport of probenecid have been assessed by studying the uptake of the drug in rabbit kidney tubules incubated in an electrolyte medium under various conditions. 2. The added compounds inhibited the uptake of probenecid both by kidney cortical slices and separated renal tubule preparations in the following order: p-aminohippurate less than phenol red less than bromophenol blue less than bromocresol green. A reversible competitive inhibitory effect of these organic anions on the renal accumulation of the drug was observed. 3. The Km for renal uptake of probenecid in separated tubules (0.04 mM) and the KI values calculated in this system for p-aminohippurate (0.5 mM), phenol red (0.09 mM), bromophenol blue (0.02 mM) and bromocresol green (0.015 mM) were found to be in good agreement with the corresponding KI value of probenecid and Km values of these compounds previously observed in various kidney tissue preparations. 4. On the basis of above mentioned findings, it is concluded that probenecid, p-aminohippurate and various phenolsulphonphthalein dyes are transported by the common renal organic anion transport system.


Larval consumption rates, interspecific predation, and local guild composition of egg-overwintering Agabus (Coleoptera, Dytiscidae) species in vernal ponds.
In vernal ponds in the boreal region, egg-over-wintering Agabus species form a guild that feeds mainly on larvae and pupae of aedine mosquitoes. The regular co-existence of very similar Agabus species indicates local communities not structured by interspecific competition. However, the lower number of species in local guilds than in the regional species pool poses a problem of limited membership. We suggest that the species of this guild display habitat differences mainly with respect to water temperature, pond size and prey density. In this view, habitat selection reflects body size and thermal growth response of the species, mainly in connection with larval development. We present field data from two northern Swedish vernal ponds. Based on these data, feeding experiments were performed to test the hypothesis outlined above. At a high prey density, larvae of all instars of the larger species A. erichsoni Gemm. & Har. had a significantly higher consumption rate than those of the smaller species A. opacus Aubé. At a low prey density the differences were smaller, and only the third instar larvae differed significantly. At 2° C, larvae of A. opacus had a significantly higher consumption rate than those of A. congener (Thunberg). At 15° C, no significant difference was observed. In studies of within-guild interspecific predation, always the larger larvae consumed the smaller ones. Field data show that egg hatching is spread out in time, and show interspecific differences. Consequently, the effects of unexpected droughts differ with species.


[Cavited pneumonia with Mycobacterium gastri positive culture smear].
Mycobacterium gastri is an atypical non pigmented mycobacteria infrequent in clinical practice. Few reports have been published about infections caused by microorganism, and only three of them, all before 1986, were respiratory infections. We report a case of cavitary pneumonia with sputum culture positive for Mycobacterium gastri, and we review the previous published cases. We describe a 79-years old man diagnosed of chronic obstructive pulmonary disease (COPD), with chronic respiratory failure, hypertension, Alzheimer's disease and multiple myeloma IgG lambda type IIA, with multiple previous admissions in our institution. He has again admitted because of an acute episode of cough and fever. The chest radiography demonstrated a right lower cavitary infiltrate, and the sputum culture showed growth of Mycobacterium gastri. We report a case of cavitary pneumonia in an immunocompromised patient caused by M. gastri resistant to isoniazid and pyrazinamide with fatal evolution. All of the cases previously described had a favourable outcome with the different treatment used.


Impaired target detection in schizophrenia and the ventral attentional network: Findings from a joint event-related potential-functional MRI analysis.
Schizophrenia patients have abnormal neural responses to salient, infrequent events. We integrated event-related potentials (ERP) and fMRI to examine the contributions of the ventral (salience) and dorsal (sustained) attention networks to this dysfunctional neural activation. Twenty-one schizophrenia patients and 22 healthy controls were assessed in separate sessions with ERP and fMRI during a visual oddball task. Visual P100, N100, and P300 ERP waveforms and fMRI activation were assessed. A joint independent components analysis (jICA) on the ERP and fMRI data were conducted. Patients exhibited reduced P300, but not P100 or N100, amplitudes to targets and reduced fMRI neural activation in both dorsal and ventral attentional networks compared with controls. However, the jICA revealed that the P300 was linked specifically to activation in the ventral (salience) network, including anterior cingulate, anterior insula, and temporal parietal junction, with patients exhibiting significantly lower activation. The P100 and N100 were linked to activation in the dorsal (sustained) network, with no group differences in level of activation. This joint analysis approach revealed the nature of target detection deficits that were not discernable by either imaging methodology alone, highlighting the utility of a multimodal fMRI and ERP approach to understand attentional network deficits in schizophrenia.


H-2 haplotype and the embryotoxicity of serum from nonpregnant congenic mice.
Previous studies revealed a significant association between genes at or near the H-2 complex and fetal loss. Reasoning that the maternal serum might contain one or more unknown factors that are harmful to early embryonic or fetal development, or both, we performed an embryotoxicity screen using chick embryos and serum from nonpregnant C57BL/10Sn (H-2b) and B10.A/SnSg (H-2a) congenic mice. Serum from the strain with the higher frequency of fetal loss (C57BL/10 Sn) yielded a significantly greater frequency of chick abnormality, specifically neural tube malformation and death, than the serum from the strain with the lower frequency of fetal loss (B10.A/SnSg). Further, the C57BL/10 Sn serum demonstrated a highly significant dose-response. These results suggest that analogous studies may be profitable with women who have a history of chronic fetal wastage and/or offspring with neural tube defects.


[The primiparae couple's experience of childbirth: qualitative study].
The aim of this research was to study childbirth experience for the primiparae couple. Thirty-three couples were interviewed two days after the birth in maternities. For mothers, the presence of their husbands is a support whereas men mentioned a feeling of helplessness. These results point out the need to accompany mothers and fathers during birth preparation to make this experience to be the most satisfying for both members of couple.


A Case Study: What Doses of Amanita phalloides and Amatoxins Are Lethal to Humans?
There are few data estimating the human lethal dose of amatoxins or of the toxin level present in ingested raw poisonous mushrooms. Here, we present a patient who intentionally ingested several wild collected mushrooms to assess whether they were poisonous. Nearly 1 day after ingestion, during which the patient had nausea and vomiting, he presented at the emergency department. His transaminase levels started to increase starting from hour 48 and peaking at hour 72 (alanine aminotransferase 2496 IU/L; aspartate aminotransferase 1777 IU/L). A toxin analysis was carried out on the mushrooms that the patient said he had ingested. With reversed-phase high-performance liquid chromatography analysis, an uptake of approximately 21.3 mg amatoxin from nearly 50 g mushroom was calculated; it consisted of 11.9 mg alpha amanitin, 8.4 mg beta amanitin, and 1 mg gamma amanitin. In the urine sample taken on day 4, 2.7 ng/mL alpha amanitin and 1.25 ng/mL beta amanitin were found, and there was no gamma amanitin. Our findings suggest that the patient ingested approximately 0.32 mg/kg amatoxin, and fortunately recovered after serious hepatotoxicity developed.


Phenotypic assessment of Neisseria meningitidis isolates obtained from patients with invasive meningococcal disease in Greece, 1993-2003: implications for serogroup B vaccines based on PorA serosubtype antigens.
Serogroup B is the major isolate from patients with invasive meningococcal disease (IMD) in Greece. This study used the whole cell enzyme-linked immuosorbent assay (ELISA) with monoclonal antibodies to screen Neisseria meningitidis isolates obtained from patients with IMD between 1993 and 2003 to determine if serosubtypes included in the hexavalent Por A OMP vaccines being tested in northern Europe were prevalent in Greece. During this period there were significant changes in the proportions of serogroups B and C isolated from patients. Serogroup C was predominant in 1996-1997 but fell sharply with corresponding increases in serogroup B. Of the 591 isolates sent to the National Meningitis Reference Laboratory in Athens during this period, 325 (55%) were serogroup B. Among those tested for serosubtype, porA proteins used for the vaccine being tested in Britain were detected on 85/284 (30%) strains and for the vaccine being tested in the Netherlands 175/284 (62%). P1.14 (58/284, 20%) the predominant serosubtype among the Greek isolates, is not present in either vaccine formulation; 23/284 (8%) strains did not react with any of the monoclonal antibodies. Our results indicate that introduction of the vaccines currently being evaluated in northern Europe would not be warranted in the Greek population.


Isolation of Legionella anisa from a hospital hot water system.
Several cases of Legionnaires' disease occurred in a French hospital in 1982. Thirteen strains of a legionella-like organism with several unusual characteristics were subsequently isolated from the hospital hot water system. The various features of these strains show that they are identical to the new species 'Legionella anisa' described by the Centers for Disease Control. The possible pathogenicity of these strains to man and their relationship with the recently described Legionella bozemanii serogroup 2 are discussed.


Comparative analysis of the basement membrane composition of the human limbus epithelium and amniotic membrane epithelium.
Human amniotic membrane has been widely used as substrate for ex vivo expansion and transplantation of limbal epithelial cells. To further clarify its suitability as a surrogate niche for limbal stem cells and progenitor cells, we analyzed the composition of the amniotic epithelial basement membrane, with special focus on the expression of limbus-specific matrix components. Cryosections of corneoscleral specimens obtained from 10 human donor eyes and of 6 amniotic membrane specimens obtained at cesarean section were stained by indirect immunofluorescence using a broad panel of antibodies against basement membrane components. Both amniotic and limbal epithelial basement membranes showed positive immunoreactivity for collagen type IV α1, α2, α5, and α6 chains; collagens type VII, XV, XVI, XVII, and XVIII; laminin α3, β1, β2, β3, γ1, and γ2 chains; laminin-111 and laminin-332; nidogen-1 and nidogen-2; fibronectin; fibulin-2; fibrillin-2; perlecan; and agrin. Both types of basement membrane were negative for collagen type IV α3 and α4 chains, collagen type V, and laminin α4 chain. Limbal basement membrane components, which were not detected in amniotic membrane, included laminin α1, α2, α5, and γ3 chains; BM40/SPARC; tenascin-C; matrilin-2; endostatin; and collagen type XVIII. Despite extensive similarities in basement membrane composition between amniotic and corneolimbal epithelia, the lack of limbus-specific environmental factors argues against the potential of denuded amniotic membrane as a surrogate niche for limbal stem cells but supports its suitability as a substrate to promote the formation of a well-differentiated stratified corneal epithelial equivalent for tissue engineering strategies.


Revision surgery in thoracic disc herniation.
Surgical treatment failures or strategies for the reoperation of residual thoracic disc herniations are sparsely discussed. We investigated factors that led to incomplete disc removal and recommend reoperation strategies. As a referral centre for thoracic disc disease, we reviewed retrospectively the clinical records and imaging studies before and after the treatment of patients who were sent to us for revision surgery for thoracic disc herniation from 2013 to 2018. A total of 456 patients were treated from 2013 to 2018 at our institution. Twenty-one patients had undergone previously thoracic discectomy at an outside facility and harboured residual, incompletely excised and symptomatic herniated thoracic discs. In 12 patients (57%), the initial symptoms that led to their primary operation were improved after the first surgery, but recurred after a mean of 2.8 years. In seven patients (33%) they remained stable, and in two cases they were worse. All patients were treated via all dorsal approaches. In all 21 cases, the initial excision was incomplete regarding medullar decompression. All of the discs were removed completely in a single revision procedure. After mean follow-up of 24 months (range 12-57 months), clinical neurological improvement was demonstrated in seven patients, while three patients suffered a worsening and 11 patients remained stable. Our data suggest that pure dorsal decompression provides a short relief of the symptoms caused by spinal cord compression. Progressive myelopathy (probably due to mechanical and vascular deficits) and scar formation may cause worsening of symptoms. These slides can be retrieved under Electronic Supplementary Material.


Dose-limiting complications from upper half body irradiation in C3H mice.
This investigation evaluates the usefulness of an experimental technique in mice that has been used to study lung tolerance as a major dose-limiting tissue in clinical radiotherapy. The pathological sequalae of upper half body irradiation using a range of single and fractionated (2 Gy per fraction once or twice daily) doses was characterized in C3H/HeJ mice. Four phases of potentially lethal syndromes were revealed starting with the very acute effects of oral inflammation within 1 month. Incisor damage occurred between 1 and 3 months when the supplying of powdered food appeared to prevent lethality from starvation. Single radiation doses then produced a predictable incidence of pneumonitis (3 to 6 months) followed by pleural effusions (6 to 12 months). These later two syndromes were absent in mice that survived the acute effects of fractionated UHBI. In accordance with other rapidly proliferating tissues, the estimated alpha/beta ratios for oral epithelial and incisor damage were notably larger than that previously reported for lung. This denotes the smaller capacity of the acute responding target cells to repair sublethal damage. The consequent predominance of acute reactions in the fractionated courses therefore confined the maximal tolerated dose to that which produced an unmeasurable level of pulmonary injury. Our discussion of these results warn against the simple extrapolation of fractionated or low dose rate UHBI lethality data from mouse to man without due consideration of extrapulmonary radiation effects.


Aspiration biopsy cytology of prostate carcinoma.
Fine needle aspiration biopsy cytology allows safe morphologic tumor diagnosis in the prostate based on cytologic and histologic criteria. Specific technical difficulties of the procedure are not greater than in surgical pathology. The standardized equipment developed by FRANZEN is recommended. Aspiration biopsy is atraumatic and without complications. The method introduces a new clinical approach to the application of recent advances in cell research. Among other improvements, aspiration biopsy may falicitate cytologic classification of prostate carcinoma. The method should be adapted to screening programs.


Organ-specific support in multiple organ failure: pulmonary support.
The catastrophic pulmonary failure that complicates management of patients with multiple trauma or sepsis syndrome with shock is recognizable to nearly all experienced surgeons. However, the spectrum of injury is broad, the distribution of lung injury may be heterogeneous within a single patient, and many patients will not develop acute respiratory distress syndrome (ARDS) even after a major predisposing insult. The lung responds stereotypically to many disparate insults, so a better conceptual construct of ARDS may be to consider it as one component of the multiple organ dysfunction syndrome. Support of oxygen transport with positive pressure ventilation and high levels of positive end-expiratory pressure, long the mainstay of pulmonary support, has been criticized for its predilection to cause barotrauma. Newer modes of ventilation, such as pressure-controlled, inverse-ratio ventilation and permissive hypercapnia, are under investigation but have not yet been reported with scientific rigor. However, pulmonary support extends beyond the support of gas exchange. Fluid management requires close attention so that the circulation is supported but lung water accumulation is minimized. Nosocomial pneumonia greatly increases the mortality rate in ARDS, but is difficult to diagnose and must be sought aggressively. Until recently, pharmacologic therapy has held little promise, but inhalation of very low concentrations of nitric oxide appear to decrease pulmonary vascular pressures and intrapulmonary shunt. It remains unknown whether nitric oxide is effective therapy for the underlying injury, or is simply treatment for certain manifestations.


Does long-term swimming participation have a deleterious effect on the adult female skeleton?
Swimming is a popular activity for Australian women with proven cardiovascular benefits yet lacks the features thought necessary to stimulate positive adaptive changes in bone. Given that peak bone mass is attained close to the end of the second decade, we asked whether swimming was negatively associated with bone mineral density in premenopausal women beyond this age. Bone mass and retrospective physical activity data were gathered from 43 female swimmers and 44 controls (mean ages 40.4 and 43.8 years, respectively). Swimmers were recruited from the Australian Union of Senior Swimmers International while controls were healthy community dwellers with similar lean mass, fat mass, height, weight and body mass index. None of the participants had a history of medical complaints nor use of medications known to affect bone. Dual energy X-ray absorptiometry was used to determine areal bone mineral density at total body, lumbar spine, proximal femur, distal radius and tibia while self-administered questionnaires were used to approximate historical and recent physical activity and calcium intake. Swimmers had averaged over 2 hours of swimming per week for the past 5 years and 1.45 h/week over lifetime with no systematic swimming exposure for controls. Lifetime exposure to weight bearing and impact exercise were similar. There were no intergroup differences for bone mass at any site though controls had higher incidence of low bone mass/osteoporosis. No differences in bone mass were detected between swimmers in the upper and lower quartiles for swim participation for any period. Long-term swim participation did not compromise areal bone mineral density.


Spatial-frequency and contrast tuning of the transient-stereopsis system.
The tuning of the transient-stereopsis system to luminance contrast and spatial-frequency (SF) was investigated with narrow-band gabor targets with a constant sigma of 1 degree. They were presented for brief (140 ms) durations and subtended a large (6 degrees) disparity. When dichoptic gabor stimuli were matched in SF (0-5 cpd), transient stereo performance was either uniform across SF or greater at frequencies below 1 cpd. When dichoptic stimuli had unmatched SF (0.5 + 0-5 cpd) and matched contrast (100%), stereo performance was impaired below that of the matched SF condition. Stereo performance with matched SF at 0.5 cpd was impaired when contrast of one eye's image was reduced, demonstrating a contrast-paradox effect (i.e. contrast tuning) for transient stereopsis. Performance with three dichoptic unmatched SF conditions (0.5 and 1.0 cpd; 0.5 and 5.0 cpd; 1.5 and 3.5 cpd) was improved when the contrasts of the low SF gabor was reduced while holding the contrast of the high SF gabor constant at 100%. However stereo performance was not improved by reducing the contrast of a high SF gabor (3.5 cpd) while holding the contrast of the lower SF gabor (1.5 cpd) constant at 100%. We interpret these findings as indicating that transient-stereopsis performance is mediated by a single spatial-channel that has low-pass spatial-frequency sensitivity and which compares the ocular based signals prior to binocular combination so that signals that are not balanced in terms of their strength lead to a weaker binocular signal, as per the model proposed by Kontsevich and Tyler (Vis Res 1994; 3417:2317-2329) for sustained stereopsis.


Liver gene transfection by retrograde intrabiliary infusion facilitated by temporary biliary obstruction.
The hepatobiliary tract may be a valuable administration site for gene delivery. We demonstrated the role of temporary biliary obstruction for gene transfection by retrograde intrabiliary infusion. Male Sprague-Dawley rats received intrabiliary infusion of luciferase plasmid via an artificial common bile duct, with temporary biliary obstruction for 0 minutes (NO group), 30 minutes (30 min group) and 24 hours (24 h group), respectively (n = 4 for each group). Gene expression levels were evaluated by luciferase bioluminescence on postoperative days (POD) 1, 2 and 7. Serum and livers were collected on POD 1 and 14 for liver biochemistry, hematoxylin and eosin staining, and immunohistochemistry. On POD 1, luciferase chemoluminescence was significantly higher in the 24 h group than in the NO group (p = 0.002) and the 30 min group (p = 0.002). However, it decreased rapidly after reversal of the obstruction in the 24 h group (POD 1 versus POD 2, p = 0.002; POD 1 versus POD 7, p = 0.002). Liver biochemistry was changed on POD 1, but no significant differences were detected after 14 days of recovery (p > 0.05). Similar histological changes were found in the three groups, with no unwanted proliferation of biliary epithelial cells. The obstruction did not cause serious liver damage. Temporary biliary obstruction for 24 hours facilitated the safe, feasible and effective transfection of plasmid DNA into the liver via the hepatobiliary tract. In the future, endoscopic retrograde cholangiopancreatography and its dilation balloon could be used to create biliary obstruction and allow the direct gene delivery into the liver. More research is necessary for achieving stable gene expression, as well as in terms of weighing its benefits against potential complications.


Brain angiotensin: critical role in the ongoing regulation of body fluid homeostasis and cardiovascular function.
The existence of an endogenous brain-angiotensin system and its association with cardiovascular and body water regulation has been recognized for over a decade. Nevertheless, the importance of the brain-angiotensin system to the instantaneous regulation of these processes has not been firmly established. A 5-minute intracerebroventricular (ICV) infusion of the angiotensin antagonist, [Sar1,Thr8]-AII, effectively lowered the blood pressure in normotensive rats. Additionally, application of the selective aminopeptidase inhibitor, bestatin, given alone, resulted in a dramatic increase in blood pressure and a robust drinking response. Both effects were 100% blockable by [Sar1,Thr8]-AII pretreatment. Predictably, an aminopeptidase inhibitor, bestatin, greatly elongated the half-lives of AII and AIII in the cerebroventricles. Since neither of these treatments included the introduction of exogenous angiotensins, we have concluded that perturbations of the endogenous brain-angiotensin system are effective at rapidly influencing both cardiovascular and body fluid homeostasis, thus highlighting the paramount role played by brain angiotensin in their ongoing regulation.


Clinical comparison of the SITE IRAS hand-held interferometer and Haag-Streit Lotmar visometer.
The preoperative testing of retinal acuity was evaluated using two instruments in each of 35 eyes having extracapsular cataract extraction. Retinal acuity was measured using the SITE IRAS hand-held interferometer and the Haag-Streit Lotmar visometer. The postoperative findings are given for comparisons of final acuity, prediction, and instrument evaluation. The results showed predicted acuity to be within two lines of the final acuity in 57.1% of eyes with the Haag-Streit unit and in 42.8% of eyes with the SITE instrument. The instrument differences were more in procedure than in results.


Does standardized mega-code training improve the quality of pre-hospital advanced cardiac life support (ACLS)?
The aim of our prospective study was to evaluate the effects of a standardized mega-code and arrhythmia training upon process elements of quality of pre-hospital advanced cardiac life support provided by a physician-staffed mobile intensive care unit. In 145 cases of adult cardiac arrest due to cardiac aetiology, time intervals from arrival of the mobile intensive care unit at the patient's side until first ECG diagnosis, first defibrillation, endotracheal intubation, and first epinephrine administration were measured with on-line tape recording, prior to, and following a standardized 8-h arrhythmia and mega-code training. Following the training, patients with asystole or pulseless electrical activity were intubated 1.1 min earlier (P = 0.03), and received epinephrine 1.3 min earlier (P = 0.01) than prior to the training. There were no significant differences in time intervals concerning management of ventricular fibrillation or tachycardia. Neither admission nor discharge rates differed significantly before and after the training. Thus, practical training including rhythm analysis and mega-code session improved the performance of our mobile intensive care unit in cases of asystole and pulseless electrical activity, and, hence, process elements of quality.


High-dose intravenous proton pump inhibition following endoscopic therapy in the acute management of patients with bleeding peptic ulcers in the USA and Canada: a cost-effectiveness analysis.
The efficacy of high-dose intravenous proton pump inhibition has recently been shown, yet its cost-effectiveness remains poorly studied. To assess the cost-effectiveness of this approach separately for American and Canadian health care settings. A validated decision model included patients with bleeding ulcers after successful endoscopic haemostasis. Probabilities were determined from the literature, and charges and lengths of stay from national databases. A third-party payer perspective was adopted over a 30-day time horizon. Re-bleeding rates were 5.9% for patients who received high-dose intravenous proton pump inhibition and 22.9% for those who did not. Hospitalization costs for patients with and without re-bleeding were 11,802 US dollars and 7993 US dollars, and 5220 Canadian dollars and 2696 Canadian dollars, respectively. High-dose intravenous proton pump inhibition was more effective and less costly than the alternative of not administering it. The cost-effectiveness ratios for high-dose and no high-dose intravenous proton pump inhibition were 9112 US dollars and 11,819 US dollars (3293 dollars and 4284 dollars for the Canadian case), respectively. Sensitivity and threshold analyses showed that the results were robust across a wide range of clinically relevant assumptions. In the USA and Canada, administering high-dose intravenous proton pump inhibition for 3 days is both more effective and less costly than not doing so for patients with bleeding ulcers after successful endoscopic haemostasis.


Age-related studies on the removal of 7-methylguanine from DNA of mouse kidney tissue following N-methyl-N-nitrosourea treatment.
To investigate the effects of age on DNA repair of alkylation damage, C57BL/6NNia mice ranging from 9 months to 29 months of age were injected by the intraperitoneal route with single doses of N-methyl-N-nitrosourea (MNU). The rates of removal of 7-methylguanine (m7Gua) in nuclear DNA from kidney were determined at various intervals from 1 to 288 h after injection of either 25 mg or 50 mg MNU per kg body weight. Reversed phase HPLC with electrochemical detection was used to monitor adduct disappearance from DNA hydrolysates. The kinetics of m7Gua removal from DNA were at least biphasic. Evidence was obtained that there was a rapid removal of m7Gua occurring in the first 24 h after MNU administration, followed by a slow phase of removal with a t1/2 greater than 150 h. We assume that these two phases of m7Gua removal correspond to active repair of DNA by N-alkylglycosylases and to passive elimination via spontaneous hydrolysis, respectively. Young and old kidney tissues all exhibited significant repair of m7Gua (55-73% of the induced adducts were removed in the first 24 h), but a substantial fraction of m7Gua was removed slowly, indicating that there are methylated bases which were refractory to repair processes. At both doses of MNU studied, old tissues showed active repair of m7Gua that, within the limits of detection, had similar initial rates of removal as young tissues. However, old kidney did not remove this adduct with the same overall efficiency as young kidney. Therefore, the amount of m7Gua in the repair-resistant fraction was greater in the senescent tissues. The biochemical mechanisms responsible for the less efficient DNA repair in senescent kidney are not known, but we suggest that such differences are due in part to structural alterations in the chromatin.


Diagnosis and management of hypoaldosteronism without hypoadrenocorticism in an alpaca.
Primary hypoaldosteronism without concurrent hypoadrenocorticism was diagnosed in an 8-year-old female alpaca with acute onset of weakness progressing to recumbency within 6 hours after onset. Hematologic testing at admission revealed profound hyponatremia, hypochloremia, and acidemia with a normal blood potassium concentration. Further diagnostic testing, including an ACTH stimulation test, led to a diagnosis of hypoaldosteronism in conjunction with normal cortisol production. The hembra responded well to i.v. polyionic fluid therapy with sodium supplementation and was managed successfully long term with free access to saline (0.9% NaCl) solution in addition to water ad libitum. To our knowledge, this is the first reported case of hypoaldosteronism in an alpaca. Hypoaldosteronism should be considered in alpacas as a possible differential diagnosis for refractory hyponatremia or for hyponatremia in which an underlying etiology is not determined.


Comparative efficacy of topical povidone-iodine and chlorhexidine gel on dental plaque regrowth in toddlers: A randomized controlled trial.
This study aimed to compare and evaluate the efficacy of topical use of povidone-iodine (PVP-I) solution and chlorhexidine (CHX) gel on dental plaque regrowth after 3 and 7 days in toddlers aged 24-36 months. A randomized controlled trial that included 45 healthy toddlers aged 24-36 months, who were randomly assigned to three groups. The first group received a placebo (distilled water (DW)) (negative control). The second group received topical CHX gel (0.2% w/v) (positive control). The third group received topical PVP-I solution (10% w/v). Plaque accumulation was measured at the baseline (t0 ), after 3 days (t1 ) and after 7 days (t2 ) using the Turesky-modified Quigley-Hein plaque index (TMQHPI). Oral hygiene practices were prohibited during the trial period. The trial ID is ACTRN12623000567628. In the DW group, the mean of the TMQHPI score was 1.89 ± 0.67 at t0 and decreased to 1.45 ± 0.66 at t1 (p = .028). Similarly, in the CHX group, the mean of the TMQHPI score was 1.83 ± 1.06 at t0 and decreased to 1.02 ± 0.99 at t1 (p = .033). Regarding the PVP-I group, the mean of the TMQHPI score went from 1.84 ± 0.85 to 1.01 ± 0.61 at t1 and then increased to 1.57 ± 0.74 at t2 . Those changes were statistically significant (p = .001) and (p = .002), respectively. No statistically significant difference was noted between TMQHPI scores at t0 (p = .789). Regarding t1 and t2 , no statistically significant difference was found between the three groups (p > .05). CHX and PVP-I efficacy lasted only for 3 days, and PVP-I was not superior to CHX in terms of plaque control in toddlers. However, further studies are needed to determine the long-term efficacy of these antiplaque agents in toddlers.


Relationship between CBCT and panoramic images of the morphology and angulation of the posterior mandibular jaw bone.
We determined actual bucco-lingual angulation values and morphological variations of residual bone in the mandibular posterior edentulous region using cone-beam computed tomography (CBCT) and panoramic radiography. A second aim was to investigate whether it was possible to predict bone morphology from panoramic radiographs. Data were collected from 77 consecutive patients referred for both CBCT and panoramic radiography in our department. Two-dimensional and three-dimensional images of the probable implant placement region were investigated. The bucco-lingual angulation values and crest type were determined directly from the cross-sectional images of the posterior edentulous region. The edentulous region was divided into three groups: second premolar, first molar, or second molar region. The observations were evaluated by the computer software, SPSS 22.0 (SPSS Inc. Chicago, USA). The crest type was classified into three groups: type U, type C, or type P. Kappa statistics, Kolmogorov-Smirnov tests, ANOVA, and Kruskal-Wallis tests were used in statistical analyses. The significance level was set at p < 0.05. Type C was more frequent in the second premolar region and the crest type had changed to type U in the second molar region. The predictability of the type U was highest in the second molar region. Moderate agreement was found in the predictability of type U in the molars (κ = 0.602). The mean value of bucco-lingual angulation was highest in the second molar region, followed by the first molar region. There were statistically significant differences between the bucco-lingual angulation of the crest types in the second premolar and first molar regions (p < 0.05). Bucco-lingual angulation values and morphology change through the posterior mandible. Type U was predicted at a higher rate in the second molar region from panoramic radiographs. These results demonstrate predicting high-risk areas in the posterior mandible for implant therapy from panoramic radiography.


Socio-cultural implications of changing organizational technologies in the provision of care.
Technology refers to inputs (machines, bureaucratic procedures, management strategies) organized to achieve specified outcomes. Such inputs and how they are used arise from socio-cultural conditions and in turn influence social behavior and values. Advances in medical technology are due to the high value populations place on health, emerging developments in science (also a cultural product). and from the opportunities and incentives the society gives to varying stakeholders. In the United States for example, the development and uses of medical technology are shaped by faith in marketplace competition, technological progress, activism, choice and consumerism. This constellation of values has resulted in very rapid growth and dissemination of hardware and related procedures whose costs pose significant financial dilemmas. In response, a range of management technologies have been developed to restrain the excesses of intervention but, because they are counter to many prevailing values and interests, they have led to much tension and a social backlash. Resolving these rationing tensions--which are rarely acknowledged as such--is a major challenge in American medical care and in much of the world. In the context of American social values, once new preventive or treatment technologies are introduced, they take patients on treatment trajectories that are difficult to control and which result in many being labeled with diagnoses they do not have and receiving interventions they do not need. Major efforts are under way to increase the sophistication of consumers of health care in a manner consistent with evidence-based medicine but these face significant barriers. Underlying what at first appears as simply technical barriers are the particular social and cultural influences on how people acquire and use information, the sources they trust and distrust, and the types of information they find credible and relevant to their situations. In short, the competition between new preventive and treatment technologies and managed care technologies is at its heart a culture war.


Correction to: Incidence of clinically significant perforation at low dose non‑contrast CT and its value prior to same day CT colonography following incomplete colonoscopy.
The original version of this article has an error in the order of authors name. The order of author names should read as "Aileen O'Shea, Timothy Murray, Eavan Thornton, Michael J. Lee and Martina M. Morrin" in the authors group.


Effects of self-monitoring devices on blood pressure in older adults with hypertension and diabetes: a randomised controlled trial.
Hypertension and diabetes frequently coexist, which results in the difficulty of hypertension control in community-dwelling elderly adults who lack effective prevention and control strategies. The aim of this study is to determine whether a combined pedometer and home blood pressure monitoring (HBPM) programme could improve blood pressure (BP) among community-dwelling elderly adults with hypertension and diabetes. The trial was a 2×2 factorial randomised clinical trial that recruited 180 community-dwelling elderly people (aged ≥60) with hypertension and diabetes in Tianjin, China. Participants were randomly assigned to control, pedometer, HBPM, and pedometer+HBPM groups. Intervention period was 12 months. The coprimary outcomes of the study were systolic and diastolic BP; the secondary outcomes included the proportion of patients with controlled hypertension. BP was measured twice in the right arm using a mercurial sphygmomanometer. The mean of these two measurements was taken as the BP value. At 12 months, compared with the control group, the adjusted differences in least squares mean (95% CI) in systolic and diastolic BP changes for pedometer, HBPM, and pedometer+HBPM groups were -4.2 (-8.4 to 0.1), -2.7 (-6.9 to 1.5) and -8.1 (-12.3 to -3.9) mm Hg (p<0.01); -3.2 (-5.2 to -1.1), -0.1(-2.1 to 1.9) and -3.6 (-5.6 to -1.5) mm Hg (p<0.001), respectively; the adjusted difference in percentage (95% CI) in the controlled hypertension (BP <140/90 mm Hg) for pedometer, HBPM and pedometer+HBPM groups were 7.5 (-12.2 to 27.1), 9.9 (-10.4 to 30.3) and 23.1 (5.0 to 41.1) (p=0.09). Combination pedometer and HBPM interventions can significantly decrease BP levels in elderly adults with hypertension and diabetes. UMIN000021613.


Studies on the biosynthesis of iturin, an antibiotic of Bacillus subtilis, and a lipopeptide containing beta-hydroxy fatty acids.
The biosynthesis of iturin, an antibiotic containing a beta-amino fatty acid, was studied by incubating Bacillus subtilis in the presence of various 14C-labelled precursors. Sodium acetate or palmitic acid were incorporated into the beta-amino acids of iturin. Among the alpha-amino acids (asparagine, glutamine, serine, proline and tyrosine) in the peptidic part of iturin, asparagine appears to be the best precursor. In the presence of sodium [14C]acetate or [14C]asparagine, there was a synthesis of radioactive compound (compound X) before the synthesis of radioactive iturin. Compound X contained asparagine and/or aspartic acid, glutamine and/or glutamic acid and beta-hydroxy fatty acids.


Impact of HLA-compatibilities in patients undergoing liver transplantation for HBV-cirrhosis.
Liver transplantation (OLT) for end-stage chronic hepatitis-B-virus (HBV) infection is frequently complicated by HBV recurrence. In the present study we investigated whether human leucocyte antigen (HLA)-matching influences the outcome after OLT. In a retrospective analysis we reviewed 84 recipients of liver transplants for end-stage HBV-cirrhosis and complete HLA-typing for outcome after OLT. Follow-up ranges from 1 to 110 months (median = 55.6 months). Immunosuppression consisted of Cyclosporin A (CsA)-based quadruple induction therapy or Tacrolimus-based induction protocols. Immunoprophylaxis with hepatitis B immunoglobulin was started at OLT and continued long-term. Actuarial 1- and 5-yr graft survival figures were 90.5 and 80.4%, respectively. Hepatitis-B recurrence was responsible for 15 of 20 (75%) graft failures. We observed a significantly improved graft survival in patients with more HLA-A, -B compatibilities (p = 0.02), whereas the degree of HLA-DR compatibilities did not influence the outcome. The occurrence of HBV-reinfection was significantly lower in HLA-A, -B matched grafts (p < 0.05). Additionally, graft survival was prolonged in patients with HBV-reinfection and 1 or 2 HLA-B compatibilities when compared with patients with HBV-reinfection and a complete HLA-B mismatch (p = 0.02). In conclusion, this retrospective analysis shows that more HLA-A, -B compatibilities seems to be associated with an improved graft survival in patients after OLT for end-stage HBV infection.


Mental health during the omicron pandemic: A comparison between medical staff and non-medical staff.
A considerable number of people suffered from mental disorders due to coronavirus disease 2019 (COVID-19). As the virus mutated, the effect of COVID-19 changed. This study intends to compare the mental health between the medical staff and non-medical staff during the Omicron pandemic, and to analyze the relevant risk factors. The cross-sectional study was conducted by a set of online questionnaires, 1246 medical staff and 1246 non-medical staff were selected after a 1:1 propensity score matching. The questionnaires included the demographic characteristics, the Coronavirus Anxiety Scale (CAS), the Center for Epidemiologic Studies Depression Scale (CES-D), the Insomnia Severity Index Scale (ISI), and the Psychological Resilience Scale(CD-RISC). Compared with medical staff, non-medical staff scored higher on CAS and CES-D (both P < 0.001). Non-medical staff had higher prevalence of anxiety (55.0 % versus 47.3 %; adjusted OR = 1.45, 95 % CI = 1.23-1.70), depression (62.4 % versus 53.4 %; adjusted OR = 1.46, 95 % CI = 1.23-1.73) and insomnia (46.5 % versus 43.4 %; adjusted OR = 1.21, 95 % CI = 1.02-1.43). Multivariate logistic regression analysis showed that being female, being younger than 40 years, having an annual income of <50,000 yuan, paying attention to omicron, in the course of an infection and below bachelor degree influenced anxiety, depression and insomnia of the medical staff and non-medical staff to different degree. This study only collected data through the network. Therefore, the validity was reduced to some extent. The outbreak of the Omicron epidemic posed a significant challenge to public mental health, with non-medical staff at the highest risk for mental health problems.


Partial trisomy of 13(pter to q12) due to 47,XY, + der(13),t(13;22)(q12;q13)mat.
A 36-month-old boy presented with short stature, short neck, shield-shaped chest, and mental retardation. Chromosome analysis showed trisomy for the short arm and the proximal protion of the long arm of chromosome 13 [47,XY, + der(13),t(13;22)(q12;q13)mat]. The patient's mother has a balanced translocation between the long arms of chromosomes 13 and 22 [46,XX,t(13;22)(q12;q13)]. The patient's neutrophils showed an elevated number of nuclear projections and his fetal hemoglobin level was undetectable.


S100B in schizophrenic psychosis.
Recent findings have strengthened the hypothesis that a dysfunction of neuronal synapses and dendrites is relevant for the pathogenesis of schizophrenia. It might be present during neurodevelopment as well as in degenerative and regenerative processes of the mature brain. S1OOB, a small, Ca2+-binding, astrocytic protein, plays an important role in modulating the proliferation and differentiation of neurons and glia cells. It is involved in the regulation of cellular energy metabolism and interacts with many immunological functions of the brain. This review addresses findings from cell cultural and animal experiments potentially pertinent for the pathogenesis of schizophrenic psychoses. Morphological and functional data are analyzed and clinical studies reporting alterations of S1OOB concentrations in schizophrenic patients are reviewed. Evidence and limitations of the available studies are pointed out and promising future research strategies are outlined.


Colonic Hypersensitivity and Sensitization of Voltage-gated Sodium Channels in Primary Sensory Neurons in Rats with Diabetes.
Patients with long-standing diabetes often demonstrate intestinal dysfunction and abdominal pain. However, the pathophysiology of abdominal pain in diabetic patients remains elusive. The purpose of study was to determine roles of voltage-gated sodium channels in dorsal root ganglion (DRG) in colonic hypersensitivity of rats with diabetes. Diabetic models were induced by a single intraperitoneal injection of streptozotocin (STZ; 65 mg/kg) in adult female rats, while the control rats received citrate buffer only. Behavioral responses to colorectal distention were used to determine colonic sensitivity in rats. Colon projection DRG neurons labeled with DiI were acutely dissociated for measuring excitability and sodium channel currents by whole-cell patch clamp recordings. Western blot analysis was employed to measure the expression of NaV1.7 and NaV1.8 of colon DRGs. STZ injection produced a significantly lower distention threshold than control rats in responding to colorectal distention. STZ injection also depolarized the resting membrane potentials, hyperpolarized action potential threshold, decreased rheobase and increased frequency of action potentials evoked by 2 and 3 times rheobase and ramp current stimulation. Furthermore, STZ injection enhanced neuronal sodium current densities of DRG neurons innervating the colon. STZ injection also led to a significant upregulation of NaV1.7 and NaV1.8 expression in colon DRGs compared with age and sex-matched control rats. Our results suggest that enhanced neuronal excitability following STZ injection, which may be mediated by upregulation of NaV1.7 and NaV1.8 expression in DRGs, may play an important role in colonic hypersensitivity in rats with diabetes.


[Update of pneumonia in the elderly].
The incidence of pneumonia increases with age and contributes to morbidity and mortality in the elderly. In our setting, pneumonia is the sixth leading cause of death and the fourth most common diagnosis at discharge from acute hospitals. This article reviews current concepts in management of pneumonia in the elderly: healthcare-associated pneumonia, aspiration and oropharyngeal dysphagia, risk stratification, and indications of radiological, microbiological and biological markers. We present current evidence on antibiotic treatment (when to start, empirical coverage, duration, new drugs and combinations) and adjuvant treatment (steroids, early mobilization, oral hygiene, prevention and treatment of aspiration and cardiac complications). We emphasize preventive aspects and considerations regarding palliative treatment.


Comparison of immunoaffinity columns with Florisil/C18 columns for the determination of aflatoxins in animal feed and maize.
A study of the performance of the EC method and an Immunoaffinity method for aflatoxins B1,B2,G1 and G2 in animal feed and maize was performed. The extraction and HPLC analysis of both procedures were comparable,hence a direct comparison of the performance of the alternative clean- up columns was made. Throughout the study the results were similar for both methods,however,the main advantage of the Immunoaffinity method was fewer manipulations were required. Therefore the method was easier to use,less solvent was required and greater sample throughput (approximately 2 fold) was obtained.


Aerosols for systemic treatment.
The development of a new group of drugs (polypeptides) have recently increased the interest of alternative administration to the enteral route because of its proteolytic activity and the catabolism of the "first-pass effect." Aside from the "needle," the administration in the respiratory tract via aerosol is the method with the best efficiency. But several problems prohibited its spreading: (1) the accuracy and the reproducibility of the inhaled dose (range ca. 1:4); (2) the small amount of inhaled drug in relation to the dose in the aerosol delivery system (range ca. 1%-10%); (3) the fear of allergic reactions of the respiratory system; (4) the variability of the drug transport into the systemic circulation. New approaches and data raise hopes in reducing the problems: (1) aerosol delivery systems with defined particle spectrum and storage systems; slow vital capacity inhaling maneuver; (2) delivery systems that nebulizes nearly the total amount of drug; (3) all studies with the inhalation application of insulin, heparin, ergotamin, ribavirin, aminoglycosides, and "cigarette smoke" do not reveal any relevant allergic reaction; (4) many studies were performed in the last 10 years on the influence of substances and especially of diseases on the transport of molecules through the respiratory tract. Only a few of them are relevant (exogen allergic alveolitis, active sarcoidosis, active smoking). Aerosols for (exogen allergic alveolitis, active sarcoidosis, active smoking). Aerosols for systemic drug treatment seems to be a gained alternative to the "syringe."


Multicenter phase II study of modified FOLFOX6 as neoadjuvant chemotherapy for patients with unresectable liver-only metastases from colorectal cancer in Japan: ROOF study.
Neoadjuvant chemotherapy for unresectable colorectal liver metastases can reduce tumor size, which sometimes leads to curative resection. The aim of the present study was to identify and describe patients with initially unresectable liver-only metastases from colorectal cancer who obtained sufficient chemotherapeutic benefit that eventually lead to the removal of the metastatic diseases in the liver. A phase II multicenter cooperative study was conducted in 38 medical institutions using modified FOLFOX6 (mFOLFOX6) as neoadjuvant chemotherapy from January 2008 to June 2009. Patients with liver-only metastases from colorectal cancer that was deemed not optimally resectable by liver surgeons received mFOLFOX6 as preoperative neoadjuvant chemotherapy for 6-8 cycles. Patients were reassessed for resectability after 6 cycles of mFOLFOX6. Surgery was carried out 3-6 weeks after chemotherapy. The primary endpoint was the rate of macroscopic curative surgery including liver resection. 36 patients (23 male/13 female, ECOG performance status 0-1) were enrolled. The median age of the patients was 62.5 years; 78% (28 patients) had 5 or more metastatic tumors, and 50% (18 patients) had metastatic tumors over 5 cm diameter. The mFOLFOX6 regimen was safety administered resulting in 18 partial responses (50%), 12 stable disease, and 4 progressive disease. There was no grade 3/4 neurotoxicity. Fourteen patients (38.9%) underwent surgery (R0: 13; R1: 1). Of these, thirteen patients (36.1%) underwent R0 surgery. Our data suggest that mFOLFOX6 has a high response rate in patients with liver-only metastases from colorectal cancer, allowing for R0 resection of liver metastases in a proportion of patients initially not judged to be optimally resectable.


Comparison of clofibrate and chlorpropamide in vasopressin-responsive diabetes insipidus.
Six patients with vasopressin-responsive diabetes insipidus (DI) received clofibrate and chlorpropamide, singly and in combination. Decrease in urinary output averaged (mean +/- SEM): (1) clofibrate 2 g/day, 47% +/- 6%; (2) chlorpropamide 250 mg/day 59% +/- 5%; (3) clofibrate 2 g/day plus chlorpropamide 125 mg/day, 54% +/- 7%; (4) clofibrate 2 g/day plus chlorpropamide 250 mg/day 61% +/- 4%. Water deprivation tests before and during treatment showed significantly higher basal, final, and peak urinary osmolalities (Uosm) and lower free water clearance (CH20) on chlorpropamide, singly and in combination: clofibrate raised Uosm less but significantly decreased CH2O. Water load tests before and during treatment showed that chlorpropamide, singly and in combination, markedly decreased maximal urinary flow, maximal CH2O, percentage water load excreted, and increased minimal Uosm; clofibrate significantly decreased maximal urinary flow and CH2O only. One patient responded only to combination therapy. Chlorporpamide caused serious hypoglycemia in three of six patients. Clofibrate had no significant side effects.


Comparison of the in vitro action and interaction of cefotaxime and desacetylcefotaxime against clinical isolates of Bacteroides spp.
Desacetylcefotaxime (dCTX), the in vivo metabolite of cefotaxime (CTX), possess significant in vitro antimicrobial activity similar to the parent compound against a variety of aerobic and anaerobic bacteria. In vitro susceptibility studies showed that CTX inhibited 86% of 473 strains of the Bacteroides fragilis at a concentration of 32 micrograms/ml while dCTX inhibited 91% of the test isolates at the same concentration. Strains of the B. fragilis species were significantly more susceptible to CTX than were the non-B. fragilis species. Susceptibility testing of CTX and dCTX in a 1:1 ratio produced significantly more inhibitory activity, especially against the non-B. fragilis strains. Synergy studies showed that the interaction of CTX and dCTX was either completely or partially synergistic against 85% of 92 test organisms. The presence of dCTX was also shown to lower the CTX MIC values four-fold or greater in 82% of the synergy studies. Synergy was noted against strains of the B. fragilis group, B. melaninogenicus group, B. bivius, B. disiens, and B. capillosus. Through the use of time-kill kinetics studies, the interaction of CTX and dCTX was shown to be additive at subinhibitory and inhibitory concentrations and suggestedly synergistic at suprainhibitory concentrations against strains of the B. fragilis group. These in vitro studies demonstrate that dCTX increases the inhibitory and bactericidal activity of CTX when tested in combination.


Indole derivatization procedures for electron capture negative chemical ionization mass spectrometry: identification of 1-methyl-1,2,3,4-tetrahydro-beta-carboline in rat brain and lung.
Procedures have been developed for the isolation of pharmacologically active indole compounds from biological samples and for the introduction of electron-capturing groups, pentafluorobenzyl and trifluoroacetyl, onto the indole nitrogen atom. The resulting derivatives have good gas chromatographic properties and strong electron affinities which make them highly suitable for detection by electron capture negative chemical ionization mass spectrometry. These procedures were used to identify 1-methyl-1,2,3,4-tetrahydro-beta-carboline as a component of rat brain and lung.


Comprehensive dynamic and kinematic analysis of the rodent hindlimb during over ground walking.
The rat hindlimb is a frequently utilized pre-clinical model system to evaluate injuries and pathologies impacting the hindlimbs. These studies have demonstrated the translational potential of this model but have typically focused on the force generating capacity of target muscles as the primary evaluative outcome. Historically, human studies investigating extremity injuries and pathologies have utilized biomechanical analysis to better understand the impact of injury and extent of recovery. In this study, we expand that full biomechanical workup to a rat model in order to characterize the spatiotemporal parameters, ground reaction forces, 3-D joint kinematics, 3-D joint kinetics, and energetics of gait in healthy rats. We report data on each of these metrics that meets or exceeds the standards set by the current literature and are the first to report on all these metrics in a single set of animals. The methodology and findings presented in this study have significant implications for the development and clinical application of the improved regenerative therapeutics and rehabilitative therapies required for durable and complete functional recovery from extremity traumas, as well as other musculoskeletal pathologies.


Inflammatory biomarkers to predict the prognosis of acute bacterial and viral infections.
Mortality in acute infections is mostly associated with sepsis, defined as 'life-threatening organ dysfunction caused by a dysregulated host response to infection'. It remains challenging to identify the patients with increased mortality risk due to the high heterogeneity in the dysregulated host immune response and disease progression. Biomarkers reflecting different pathways involved in the inflammatory response might improve prediction of mortality risk (prognostic enrichment) among patients with acute infections by reducing heterogeneity of the host response, as well as suggest novel strategies for patient stratification and treatment (predictive enrichment) through precision medicine approaches. The predictive value of inflammatory biomarkers has been extensively investigated in bacterial infections and the recent COVID-19 pandemic caused an increased interest in inflammatory biomarkers in this viral infection. However, limited research investigated whether the prognostic potential of these biomarkers differs between bacterial and viral infections. In this narrative review, we provide an overview of the value of various inflammatory biomarkers for the prediction of mortality in bacterial and viral infections.