Selective oxidative protection leads to tissue topological changes orchestrated by macrophage during ulcerative colitis.
Ulcerative colitis is a chronic inflammatory bowel disorder with cellular heterogeneity. To understand the composition and spatial changes of the ulcerative colitis ecosystem, here we use imaging mass cytometry and single-cell RNA sequencing to depict the single-cell landscape of the human colon ecosystem. We find tissue topological changes featured with macrophage disappearance reaction in the ulcerative colitis region, occurring only for tissue-resident macrophages. Reactive oxygen species levels are higher in the ulcerative colitis region, but reactive oxygen species scavenging enzyme SOD2 is barely detected in resident macrophages, resulting in distinct reactive oxygen species vulnerability for inflammatory macrophages and resident macrophages. Inflammatory macrophages replace resident macrophages and cause a spatial shift of TNF production during ulcerative colitis via a cytokine production network formed with T and B cells. Our study suggests components of a mechanism for the observed macrophage disappearance reaction of resident macrophages, providing mechanistic hints for macrophage disappearance reaction in other inflammation or infection situations.


Enzyme replacement therapy and substrate reduction therapy in lysosomal storage disorders with neurological expression.
Lysosomal storage diseases (LSD) are inborn errors of metabolism secondary to lysosomal enzyme defects and are characterized by a progressive accumulation of nondigested macromolecules provoking cellular dysfunction and clinical manifestations. The diagnosis of these diseases can be confirmed easily in most cases by immuno-enzymatic techniques and molecular biology. Even though these enzymatic deficits result in an accumulation of pathological substrates, the underlying mechanisms responsible for the pathogenesis of the disease are not entirely known. Nevertheless, the distribution of the accumulated material determines the affected organs. More particularly in the central nervous system (CNS), neurons are often involved due to the accumulation of storage material and their incapacity of renewal. LSD can be responsible for mental retardation or for a neurodegenerative course in the central nervous system. The peripheral nervous system and the muscle can also be severely impaired. Hematopoietic stem cell transplantation was the first therapy, demonstrating efficacy especially on the neurological involvement of various LSD. Enzyme replacement therapy is now available for Gaucher disease, Fabry disease, mucopolysaccharidoses type I, type II, and type VI, and Pompe disease. Inhibition of the synthesis of the accumulated substrate by small molecules which also have the capacity to diffuse through the blood-brain barrier is another treatment option. New therapeutic strategies using the properties of molecular chaperones and of read-through molecules for nonsense mutations have been studied in vitro and hopefully will soon find clinical applications while intrathecal enzymes are currently studies in clinical trials for MPSII, MPS IIIA and MLD.


Unnecessary laryngeal irradiation in the IMRT era.
The purpose of this review is to address the issue of unnecessary irradiation of the normal larynx. We performed a literature review and dosimetry evaluation of intensity modulated radiotheraphy (IMRT) techniques. Data suggest that matching conventional parallel opposed photon fields through adenopathy is a reasonable alternative to the common practice of unnecessarily irradiating the normal larynx to high doses. The dosimetry evaluation demonstrates that the laryngeal dose is much higher when the entire neck is included in the IMRT field as opposed to using a standard anterior low-neck field below the level of the thyroid notch. Lateral opposed fields should not be extended to include the larynx to avoid matching fields through adenopathy. IMRT fields should not include the normal larynx when the laryngeal dose would be substantially lower with a technique that shields the larynx in an anterior low-neck field.


The relationship between leukemoid reaction and perinatal morbidity, mortality, and chorioamnionitis in low birth weight infants.
Neonatal leukemoid reaction (NLR) is relatively rare and considered as a white blood cell (WBC) count ≥50×10(9)/l . The aim of this study was to investigate the association of NLR with neonatal morbidity and mortality and maternal chorioamnionitis in low birth weight infants. In this case-controlled retrospective study, the medical records of 1200 newborn infants with a birth weight <2500g admitted to the neonatal unit over a period of 5 years were reviewed. The infants who developed features of NLR (n=17, 1.4%) formed the study group, while the remainder without NLR, matched for gestational age and birth weight (n=123), formed the control group. A chart review was performed and salient demographic, clinical, and laboratory data abstracted. A statistical analysis was subsequently performed on this data. The mean WBC and absolute neutrophil counts of infants with NLR were significantly higher than those in the control group. The peak time of NLR was at 7.9±3.6 (interquartile range (IQR) 1-30) days and on average it improved within 4.1±1.95 (IQR 2-9) days. It was noted that those infants with NLR were mostly born by vaginal delivery and their mothers had a higher rate of early rupture of the membranes and chorioamnionitis. NLR was associated with a 4-fold increase in sepsis, 20-fold increase in intraventricular hemorrhage, 54-fold increase in bronchopulmonary dysplasia, and 6-fold increase in mortality. In the study group, those infants whose mothers had chorioamnionitis had a higher rate of early rupture of the membranes and they developed sepsis and intraventricular hemorrhage more often than those whose mothers did not have clinical chorioamnionitis. In low birth weight newborn infants, NLR is significantly associated with sepsis, intraventricular hemorrhage, bronchopulmonary dysplasia, and a high mortality rate. Also, those infants with NLR are more likely to be born to mothers with chorioamnionitis and they face sepsis and intraventricular hemorrhage more often.


Output performance of the novel active transcutaneous bone conduction implant Sentio at different stimulation sites.
The output performance of a novel semi-implantable transcutaneous bone conduction device was compared to an established percutaneous bone-anchored hearing system device using cadaver heads. The influence of actuator position, tissue growth below the actuator and mounting it on the surface or in a flattened bone bed on the performance of the implanted actuator was investigated. The percutaneous and the new transcutaneous device were sequentially implanted at two sites in five human cadaver heads: 55 mm superior-posterior to the ear canal opening (position A) and, closer to the cochlea, about 20 mm inferior-posterior to the ear canal opening behind the pinna on the mastoid (position B). The ipsi- and contralateral cochlear promontory (CP) velocity magnitude responses to percutaneous and transcutaneous stimulation were measured using laser Doppler vibrometry. In addition, the CP vibration of the transcutaneous device placed directly on the skull bone surface was compared with the placement in a flattened bone bed at a depth of about 3 mm. Finally, the influence of placing a thin silicone interposition layer under the implanted transducer was also explored. The percutaneous device provided about an 11 dB higher average CP vibration level than the transcutaneous device at frequencies between 0.5 and 10 kHz. The ipsilateral CP vibration responses with stimulations at position B were on average 13 dB higher compared to stimulation at position A. The placement of the transcutaneous transducer at position B provided similar or higher average vibration magnitudes than the percutaneous transducer at position A. The 3 mm deep flattened bone bed had no significant effects on the output performance. Placing a thin silicone layer under the transcutaneous transducer had no significant influence on the output of the transcutaneous device. Our results using the CP vibration responses show that at frequencies above 500 Hz the new transcutaneous device at position B provides similar output levels as the percutaneous device at position A. The results also indicated that neither a bone bed for the placement of the transcutaneous transducer nor a simulated tissue growth between the actuator and the bone affect the output performance of the device.


Wonder or fake - investigations in the case of the stigmatisation of Therese Neumann von Konnersreuth.
We investigated two compresses used by Therese Neumann (T.N.), a woman who lived from 1898 until 1962 in Konnersreuth, Germany. The compresses were soaked with blood during the appearance of stigmata on T.N.'s body on a Friday. T.N. became very popular among the faithful in Germany at this time. The question was whether this blood was from T.N. herself or from a family relative or an animal. The comparison of the HV1 and HV2 mtDNA sequence obtained from the compresses with the sequences from a reference sample from a maternally related niece of T.N. revealed an identity. Furthermore, we obtained a short tandem repeat (STR) profile from the bloodstains that were identical with the STR profile from a gummed envelope. The envelope contained a letter written by T.N. in the 1930s. Therefore, our investigations gave no indication for any manipulation.


Supported Ce/Zr pyrochlore monolayers as a route to single cerium atom catalysts with low temperature reducibility.
The combination of structural characterization at atomic resolution, chemical data, and theoretical insights has revealed the unique nanostructures which develop in ceria supported on yttria-stabilized zirconia (YSZ) after being submitted to high-temperature reducing treatments. The results show that just a small ceria loading is needed for creating a supported Zr-rich pyrochlore (111) nanostructure, resembling the structure of single cerium atom catalysts. The specific atomic arrangement of this nanostructure allows to explain the improvement of the reducibility at low temperature. The reduction mechanism can be extrapolated to ceria-zirconia mixed oxides with pyrochlore-like cationic ordering, exposing Zr-rich (111) surfaces. The results gathered here provide key information to understand the redox behavior of these types of systems, which may contribute to improving the design of new ceria-zirconia based materials, with lower content of the lanthanide element, nearly 100% cerium atom utilization, and applications in environmental catalysis.


Comparative investigation of keratin-filaments in normal tissues and tumours of skin, oral mucosa, salivary glands and thymus.
Antibodies against different fractions of keratins can be helpful in various fields of special pathology. Antibodies against "small" and "large" keratins permit to evaluate epithelial maturation in skin and oral mucosa. In addition, disturbances of keratinization during inflammatory processes and malignant transformation can be analyzed. The main application of antibodies against the entire fractions of keratins is the detection of the epithelial nature of a neoplasm. By this tool, particular problems in surgical pathology concerning differential diagnosis can be handled in an easier way. Among the different tissues and their neoplasms, examples of the analysis of thymus tumours and salivary gland tumours are presented. Immunoreactivity with keratin antibodies depends crucially on tissue processing. In the normal diagnostic procedure, good results are regularly obtained if cryostat or Bouin-fixed paraffin-embedded sections are used.


[Effects of various methods on the determination of dietary fiber and available carbohydrates on the calculation of the energy content of bread].
The dietary fiber content of German breads was determined by two different methods. With a modified NDF-method 60% of total dietary fiber (determined by an enzymatic-chemical procedure) are detected. For estimation of the physiological fuel value the main components of breads were determined by analysis. In addition, the carbohydrates were determined by difference, using various methods of calculation. For the estimation of the caloric value, different calorie conversion factors are used.


Multicentre study 'rehabilitation of occupational skin diseases -optimization and quality assurance of inpatient management (ROQ)'-results from 12-month follow-up.
Occupational skin disease (OSD) is common, and imposes a considerable personal and public burden. To tackle OSD, the German stepwise procedure of handling OSD was set up. It contains an interdisciplinary, integrated inpatient rehabilitation measure [tertiary individual prevention (TIP)] [dermatological treatment and diagnostic procedures, and patient education (health and psychological)]. The primary aims of the TIP are reduction of the severity of OSD, reduction in the use of corticosteroids, facilitation of return to work, decreased absence from work, and enhanced quality of life (QoL). It was positively evaluated for a period of 4 weeks after return to work. To investigate whether the observed short-term effects remain significant and meaningful over a period of 12 months after discharge from the TIP. A prospective design was used to compare clinical and patient-reported outcome data between admission to a 3-week inpatient TIP and 12 months after discharge (12-month follow-up). Of 1788 individuals admitted to the TIP, data from 1617 individuals were available for analysis. We observed a significant reduction in the severity of OSD, the use of topical corticosteroids, and days of absence from work because of OSD. QoL was significantly improved, and 87.4% were able to return to work and remain in the workforce. A randomized controlled trial would have been desirable, but was not possible, for legal and other reasons. However, the long-term 12-month follow-up shows that the TIP is associated with sustained improvements in terms of ability to work, QoL, and prognosis, and reductions in days of absence from work because of skin conditions and topical corticosteroid application. These results indicate that the TIP provided a reduction in the personal and public burden of OSD.


Sustained strenuous exercise in sled dogs depresses three blood copper enzyme activities.
Studies show mixed conclusions about acute responses of copper status to strenuous exercise. Because copper function involves metalloenzyme activities, which might take days to change, the present study examined the response of three copper metalloenzyme activities to sustained strenuous exercise in sled dogs. A race lasting 12-15 d depressed activities for both plasma ceruloplasmin and erythrocyte superoxide dismutase in dogs consuming commercial dog foods and meats. A shorter, 3-d training run for dogs fed a commercial balanced diet also depressed ceruloplasmin activities but not superoxide dismutase activities. Dogs fed the same diet but that did not run showed no changes in either parameter. Activities of a third copper enzyme, plasma diamine oxidase, also decreased after a 3-d training run. In summary, blood activities of three copper enzymes were depressed by sustained strenuous exercise in sled dogs.


Multimodal CT imaging and recanalizing therapy in acute ischemic stroke: retrospective analysis of a one-year single-center experience.
Recanalizing therapy in ischemic stroke is restricted to thrombolysis within 3 h. Multimodal imaging of vessel and parenchymal perfusion status may allow the extension of this time window. To retrospectively analyze treatment results of any recanalizing therapy in clinical practice. Patients comprised three groups: 'standard' intravenous thrombolysis within 3 h; 'off-label' intravenous thrombolysis, and off-label interventional therapy. Recanalizing therapy was applied dependent on multimodal CT according to standardized pathways. Short-term clinical courses were analyzed. Of 543 patients (ischemic stroke, TIA), 68 (12.5%) received some type of recanalizing therapy. Of these, 47 (mean age 73.4, 24 female, mean symptom onset and hospital admission 62 min) received standard and 10 off-label thrombolysis (70.8, 6 female, 332 min), and 11 interventional therapy, mostly mechanical thrombectomy (mean age 62.5, 7 female, 186 min). Mean Δ short-term National Institutes of Health Stroke Scale (2-5 days) in these three groups were 3.7 ± 4.7, 3.9 ± 4.4, and 4.1 ± 5.8, respectively. The short-term clinical benefit was similar in the three groups. Off-label therapy is considered to have a higher risk of complications. However, if multimodal CT imaging of acute ischemic stroke is incorporated in everyday clinical decision-making, the rate of effective recanalizing procedures may be increased without an apparent negative effect on short-term outcome.


Spectroscopic diagnosis of esophageal cancer: new classification model, improved measurement system.
Laser-induced fluorescence spectroscopy was used to measure fluorescence emission of normal and malignant tissue during endoscopy in patients with esophageal cancer and volunteers with normal esophagus. The spectroscopy system consisted of a nitrogen-pumped dye-laser tuned at 410 nm for excitation source, an optical multichannel analyzer for spectrum analysis, and a fiberoptic probe designed for both the delivery of excitation light and the collection of fluorescence emission from tissue. The fluorescence lineshape of each spectrum was determined and sampled at 15-nm intervals from 430 to 716 nm. A calibration set of spectra from normal and malignant spectra was selected. Using stepwise discriminate analysis, significant wavelengths that separated normal from malignant spectra were selected. The intensities at these wavelengths were used to formulate a classification model using linear discriminate analysis. The model was then used to classify additional tissue spectra from 26 malignant and 108 normal sites into either normal or malignant spectra. A sensitivity of 100% and specificity of 98% were obtained.


In Silico, In Vitro, and Clinical Investigations of Cathepsin B and Stefin A mRNA Expression and a Correlation Analysis in Kidney Cancer.
The cysteine protease Cathepsin B (CtsB) plays a critical role in multiple signaling pathways, intracellular protein degradation, and processing. Endogenous inhibitors regulate its enzymatic activity, including stefins and other cystatins. Recent data proved that CtsB is implicated in tumor extracellular matrix remodeling, cell invasion, and metastasis: a misbalance between cathepsins and their natural inhibitors is often considered a sign of disease progression. In the present study, we investigated CtsB and stefin A (StfA) expression in renal cell carcinoma (RCC). mRNA analysis unveiled a significant CTSB and STFA increase in RCC tissues compared to adjacent non-cancerogenic tissues and a higher CtsB expression in malignant tumors than in benign renal neoplasms. Further analysis highlighted a positive correlation between CtsB and StfA expression as a function of patient sex, age, tumor size, grade, lymph node invasion, metastasis occurrence, and survival. Alternative overexpression and silencing of CtsB and StfA confirmed the correlation expression between these proteins in human RCC-derived cells through protein analysis and fluorescent microscopy. Finally, the ectopic expression of CtsB and StfA increased RCC cell proliferation. Our data strongly indicated that CtsB and StfA expression play an important role in RCC development by mutually stimulating their expression in RCC progression.


Clinical history, brain metabolism, and neuropsychological function in Alzheimer's disease.
Data concerning 7 patients with a diagnosis of presumptive Alzheimer's disease (mean age, 65.6 years) are presented in detail in relation to the patients' regional cerebral metabolic rates for glucose. Rates were measured by positron emission tomography with fluorine 18-labeled fluoro-2-deoxy-D-glucose under conditions of reduced visual and auditory stimulation. A relationship was found between severity of dementia and brain metabolism. In patients with mild to moderate Alzheimer's disease, memory and intellectual deficits were evident without major reductions in absolute metabolic rates, while ratios of regional to whole brain metabolism revealed reductions in regions of the parietal lobes. In the late, severe form of the disease, brain metabolic rates were consistently and significantly reduced. The findings suggest that memory and intellectual deficits are reflected in reductions of brain metabolism in some brain regions in mild to moderate forms of Alzheimer's disease and that, in the late, severe form of the disease, reductions occur consistently throughout the brain.


DNA Aptamers for the Characterization of Histological Structure of Lung Adenocarcinoma.
Nucleic acid aptamers are becoming popular as molecular probes for identification and imaging pathology and, at the same time, as a convenient platform for targeted therapy. Recent studies have shown that aptamers may be effectively used for tumor characterization and as commercially available monoclonal antibodies. Here we present three DNA aptamers binding to whole transformed lung cancer tissues, including tumor cells, connective tissues, and blood vessels. Protein targets have been revealed using affinity purification followed by mass spectrometry analyses, and they have been validated using a panel of correspondent antibodies and 3D imaging of tumor tissues. Each of the proteins targeted by the aptamers is involved in cancer progression and most of them are crucial for lung adenocarcinoma. We propose the use of these aptamers in aptahistochemistry for the characterization of the histological structure of lung adenocarcinoma. The value of the presented aptamers is their application together or separately for indicating the spread of neoplastic transformation, for complex differential diagnostics, and for targeted therapy of the tumor itself as well as all transformed structures of the adjacent tissues. Moreover, it has been demonstrated that these aptamers could be used for intraoperative tumor visualization and margin assessment.


The role of CYP enzymes in cocaine-induced liver damage.
Cocaine is hepatotoxic in several species, including man. A high dose of cocaine produces metabolism-dependent, mainly pericentral, liver damage. At 24 h after a single dose of cocaine, mouse hepatic P450 content decreases but CYP2A activities; coumarin 7-hydroxylase and testosterone 15 alpha-hydroxylase increase concomitant with prominent diffuse cell necrosis. Repeated administration of cocaine for up to 5 days decreases CYP1A1/2, 2A4/5, 2Cx, and 2E1 related enzymatic activities. However, after five doses of cocaine, CYP2B10 increases in conjunction with the healing process. In the acute phase, the increased CYP2A activities do not participate in cocaine bioactivation. CYP3A enzymes are principally responsible for the cocaine N-demethylation in human and mouse liver microsomes. The hepatic metabolic CYP enzyme profile will change during prolonged cocaine intake, this being accompanied by altered cell morphology. Possible connections to cocaine toxicity in man are discussed.


Fetal striatum- and ventral mesencephalon-derived expanded neurospheres rescue dopaminergic neurons in vitro and the nigro-striatal system in vivo.
The pathogenesis of Parkinson's disease (PD) involves ongoing apoptotic loss of dopaminergic neurons in the substantia nigra pars compacta. Local delivery of the trophic factors can rescue dopaminergic neurons and halt the progression of PD. In this study we show that fetal E11 striatum-derived neurospheres and E14.5 ventral mesencephalon (VM) -derived neurospheres (NS E11 and NSvm, respectively) are a source of factors that rescue dopaminergic neurons. First, long-term expanded NS E11 and NSvm rescued primary dopaminergic neurons from serum-deprivation induced apoptosis and promoted survival of dopaminergic neurons for 14 days in vitro and this effect was due to soluble contact-independent factor/s. Second, green fluorescent protein-expressing NS E11 and NSvm grafted into the midbrain of mice with unilateral 6-hydroxydopamine-induced Parkinsonism resulted in partial rescue of the nigro-striatal system and improvement of the hypo-dopaminergic behavioral deficit. Reverse transcription-polymerase chain reaction (RT-PCR) analysis demonstrated that intact NS E11 and NSvm expressed fibroblast growth factor-2, brain-derived neurotrophic factor (BDNF), pleiotrophin, neurotrophin-3, but not glial cell line-derived neurotrophic factor (GDNF). GDNF expression was also undetectable in vivo in grafted NS E11 and NSvm suggesting that NS-derived factor/s other than GDNF mediated the rescue of nigral dopaminergic neurons. Identification of NS-derived soluble factor(s) may lead to development of novel neuroprotective therapies for PD. An unexpected observation of the present study was the detection of the ectopic host-derived tyrosine hydroxylase (TH) -expressing cells in sham-grafted mice and NS E11- and NSvm -grafted mice. We speculate that injury-derived signals (such as inflammatory cytokines that are commonly released during transplantation) induce TH expression in susceptible cells.


Great Auricular Neuralgia: Case Series.
The great auricular nerve (GAN) arises from C2-C3 and provides innervation over the skin in the pre-auricular region, jaw angle, posteroinferior pinna, and mastoid. Although damage to the GAN has been reported following trauma or procedures nearby this nerve course, neuralgia of this nerve is uncommon with knowledge based on a handful of case reports in literature. The objective of this study is to describe the presentation, treatment, and outcome of 13 cases of GAN neuralgia. Case series. Retrospecive review of charts from 1994 to 2018 with diagnoses: "auricular neuralgia," "auricular neuritis," or "auricular neuropathy." We included subjects with neuralgic pain within the distribution of the GAN, and excluded patients with atypical facial pain, GAN neuropathy, or unclear etiology. Of 79 charts, 13 patients met criteria (age at onset 11-59; 11 women, 2 men). Pain was most often described as paroxysmal stabbing provoked by: turning the head (n = 7), touching the neck (n = 5), neck position during sleep (n = 2), jaw movement (n = 2), and other (n = 2). Seven patients received GAN blocks: all noted dramatic improvement in pain, including 3 who continued to receive serial blocks at our institution successfully for the next 2 to 5 years. Two patients successfully transitioned from GAN blocks to GAN stimulators. One patient with GAN lymphoma had resolution of pain following GAN resection. GAN neuralgia should be considered in the differential for periauricular pain. GAN blocks or stimulators may be helpful for pain management.


Human papillomavirus (HPV) DNA in penile carcinomas and in two cell lines from high-incidence areas for genital cancers in Africa.
Biopsies of 13 penile cancers (PC), from patients living in regions of Uganda with a high incidence of genital cancers, were studied for the presence, molecular characteristics and physical state of DNA related to that of human papillomavirus (HPV) types 6, 11, 16, 18, 31 and 33. HPV DNA sequences were detected in all PC specimens by dot/Southern blot analyses and by gene amplification of DNA sequences highly conserved among several HPVs. HPV 16 DNA sequences were found in one PC; DNA sequences with low homology to HPV16 or HPV18 were present in all other samples. Viral DNA is primarily integrated in the cellular DNA. To isolate and characterize a possible highly oncogenic HPV, a genomic library of the DNA extracted from the PC-8 biopsy has been constructed in the EcoRI arms of the EMBL4 phage. A single phage containing 8.30-kb HPV16-related sequences has been identified and the 3 segments of 0.45, 0.65 and 7.2 kb, released by EcoRI digestion, have been independently subcloned in pUC18 for further analysis.


[Tools for metrological support in measurements of the characteristics of devices for radionuclide diagnosis].
The application of the sets of GSO IGIM-OT, GSO IGIM allows one to introduce the unified methods for metrological surveillance in the development, production and use medical radiodiagnostic measuring instruments. Using the GSO IGIM, GSO IGIM-OT, as state reference samples of radionuclide activity in the solid radiometric source of ionizing radiation creates the common basis for metrological control of the measurement qualities of the characteristics of medical equipment used in radionuclide diagnosis.


[Synthesis of human [11-leucine]minigastrin I.--I. Preparation of the fully protected tridecapeptide amide (author's transl)].
The synthesis of the tridecapeptide amide corresponding to and 11-leucine analog of human minigastrin I is decribed. The fully protected peptide derivative was obtained by assembly of three suitably protected fragments corresponding to the sequences 1-6, 7-9 and 10-13 by the carbodiimide/N-hydroxysuccinimide method.


Dependence of the size of the initially collapsed form during the refolding of barstar on denaturant concentration: evidence for a continuous transition.
Two-site fluorescence resonance energy transfer (FRET) measurements have been made to determine how two intra-molecular distances contract in the sub-millisecond collapse reaction that occurs initially during the refolding of the small protein barstar. FRET measurements were made on two, single-Cys and single-Trp-containing mutant forms of barstar, Cys25 and Cys62, in each of which a thionitrobenzoate (TNB) adduct was attached to the cysteine thiol. In each protein, the core tryptophan, Trp53, acted as the FRET donor, and the TNB adduct, located either at C25 or at C62, acted as the FRET acceptor. The stabilities as well as observable folding kinetics of the Cys25 and Cys62 mutant proteins were found to be identical. The presence of the TNB adduct on the cysteine did not alter the stability or folding kinetics of either protein. Thus, the FRET-monitored changes in the two labeled mutant proteins, Cys25-TNB and Cys62-TNB, could be compared directly. Refolding was commenced from unfolded protein in 8M urea, and both the Trp53 to C25-TNB distance and the Trp53 to C62-TNB distance were found to contract upon dilution of urea. The extent of contraction of each distance, which was measured at a few milliseconds of refolding, was dependent continuously on the concentration of urea present during refolding, and was different for the two distances. For either FRET pair, the gradual contraction of distance with a decrease in the concentration of urea in which refolding occurs, was continuous with the contraction of the polypeptide chain that is seen with a decrease in the concentration of urea in the range in which the protein remains completely unfolded. It therefore appears that the products of the initial sub-millisecond refolding reaction of barstar are collapsed forms, whose dimensions do not change cooperatively in an all-or-none manner, but instead, change gradually with a change in concentration of urea. Thus, the sub-millisecond polypeptide chain collapse reaction of barstar upon denaturant dilution, appears to be a continuous structural transition.


Purification and characterization of OTF-1, a transcription factor regulating cell cycle expression of a human histone H2b gene.
An octamer-binding transcription factor, OTF-1, which stimulates transcription of a human histone H2b gene, has been purified from HeLa nuclear extracts. This purification was achieved through the use of DNA affinity chromatography, and the factor was unambiguously identified by renaturation of activity following SDS-polyacrylamide gel electrophoresis. The purified factor retained the ability to efficiently stimulate H2b transcription in a reconstituted in vitro system. This effect was dependent upon an intact octamer element and was observed in the absence of the other H2b promoter elements (except the TATA motif). Furthermore, this activity was not detected in nuclear extracts prepared from cells synchronized in G2, in agreement with the in vivo data showing S-phase-specific utilization of the octamer element. From these data, we conclude that we have purified the bona fide H2b transcriptional regulatory factor.


Impact of Preoperative Cholangitis on Short-term Outcomes Among Patients Undergoing Liver Resection.
The impact of preoperative cholangitis (PC) on perioperative outcomes among patients undergoing liver resection remains poorly defined. We sought to characterize the prevalence of PC among patients undergoing hepatectomy and define the impact of PC on postoperative outcomes. Patients who underwent liver resection between 2013 and 2015 were identified using the Center for Medicare Services (CMS) 100% Limited Data Set (LDS) Standard Analytic Files (SAFs). Short-term outcomes after liver resection, stratified by the presence of PC, were examined. Subgroup analyses were performed to evaluate the relationship between the timing of liver resection relative to PC. Among 7392 patients undergoing liver resection, 251 patients (3.4%) experienced PC. Patients with PC were more likely to be male (59.0% vs. 50.6%) and to have a benign diagnosis (34.3% vs. 19.8%) compared with patients without PC (both p<0.05). On multivariable analysis, PC was associated with increased odds of experiencing a complication (OR 1.54, 95%CI 1.17-2.03), extended LOS (OR 2.60, 95%CI 1.99-3.39), 90-day mortality (OR 2.31, 95%CI 1.64-3.26), and higher Medicare expenditures (OR 3.32, 95%CI 2.55-4.32). Among patients with PC, requirement of both endoscopic and percutaneous biliary drainage (OR 5.16, 95%CI 1.36-9.61), as well as liver resection < 2 weeks after PC (OR 2.92, 95%CI 1.13-7.57) were associated with higher odds of 90-day mortality. Approximately 1 in 30 Medicare beneficiaries undergoing liver resection had a history of PC. PC was associated with an increased risk of adverse short-term outcomes and higher healthcare expenditures among patients undergoing hepatectomy.


[Postoperative and posttherapeutic changes after primary bone tumors : What's important for radiologists?]
Posttreatment imaging of primary bone tumours represents a diagnostic challenge for radiologists. Depending on the primary bone tumour common radiological procedures, such as radiography, computed tomography (CT), and magnetic resonance imaging (MRI), are employed. Radiography and CT are particularly useful in benign bone tumours and in matrix-forming bone tumours. MRI comes into consideration with malignant tumour recurrence and tumoral soft tissue infiltration. Bone scintigraphy is of superior importance if a primarily multifocal manifestation of bone tumour or metastasizing tumour disease is suspected. Molecular imaging (FDG-PET and hybrid imaging, using CT) are gaining increasing importance in light of monitoring neoadjuvant chemotherapy and detecting recurrent tumour appearance. The current literature shows sensitivity and specificity values for recurrent detection of up to 92% and 93%. Diagnostic accuracy is as high as 95%, thus, exceeding accuracy values for CT (67%) and MRI (86%) by far. Likewise, this is also applicable for the assessment of the neoadjuvant chemotherapy. Moreover, PET-based modalities are able to establish prognostic statements using SUV-threshold values at baseline (especially for Ewing sarcomas). Advanced imaging techniques have made a great diagnostic step forward and have proven to be relevant and reproducible with respect to both relapse detection and treatment assessment. Furthermore, it is not clear whether a higher detection rate of early tumour recurrence will inevitably lead to better outcome and survival.


The anatomy of the subscapularis tendon insertion as applied to rotator cuff repair.
The tendons constituting the rotator cuff (RC) are often torn, and several techniques for their repair have been established. The existence of an extension of the supraspinatus tendon into that of the subscapularis has often been overlooked. The purpose of this study was to study this extension in human dissections. The possible posterolateral extension of the subscapularis tendon and the interdigitating of this extension with the supraspinatus tendon were addressed. A horizontal band of tissue 1 cm below the superior ridge of the greater tuberosity of the humerus was harvested from 43 cadavers and thus included tissue constituting the greater tuberosity, bicipital groove, and lesser tuberosity. The sample extended 2 cm medially along the lesser tuberosity and 1 cm laterally along the greater tuberosity. Macroscopic findings suggest a continuous band of tissue extending across the bicipital groove. High collagen content was microscopically confirmed at different sections, and the collagen was densely distributed along the horizontal axis of the tissue samples.


Today's medical students and the Iowa curriculum.
Physicians are naturally interested in the following generation. Charles M. Helms, M.D., associate dean, student affairs and curriculum, University of Iowa College of Medicine, offers comments on students and what they are taught.


Oxytocin decreases corticosterone and nociception and increases motor activity in OVX rats.
In the present study the effects of oxytocin administered subcutaneously (s.c.) or intravaginally (i.vag.) on spontaneous motor activity, nociceptive thresholds and plasma corticosterone levels were examined in female ovariectomized (OVX) rats. Oxytocin (1 mg/kg s.c. or 100 microg i.vag.) was administered once a day for 10 days to OVX rats. Controls received saline s.c. or cellulose gel i.vag. Spontaneous motor activity was observed in an open-field arena, nociceptive thresholds were investigated by the tail-flick test, and corticosterone and oxytocin plasma levels were measured by radioimmunassay, 3, 4 and 5 days respectively, after the end of the treatment period. Both oxytocin administered s.c. and i.vag. increased forward locomotion (p<0.05) and nociceptive thresholds (p<0.05) significantly. In addition, oxytocin s.c. increased the amount of locomotor activity (p<0.05). Plasma corticosterone levels were decreased (p<0.05) and oxytocin levels were unchanged when measured 5 days after the last administration of oxytocin s.c. or i.vag. The present data indicate that oxytocin induces a spectrum of long-lasting effects in OVX rats, including an increase in spontaneous motor activity, elevation of nociceptive thresholds and decrease of corticosterone levels. Similar effects may be induced by estrogens. In addition, these data indicate that i.vag. administration of oxytocin may be used to induce oxytocin-mediated effects.


Tophaceous pseudogout of the thoracic spine.
Calcium pyrophosphate dihydrate deposition disease (CPDD, tophaceous pseudogout) is a rare crystal arthropathy characterized by pyrophosphate crystal deposition in joints, synovitis and chondrocalcinosis on imaging. We present the case of a 72-year-old man with 6 months of left chest pain; magnetic resonance imaging revealed a T9/T10 herniated disc. Intraoperatively, the material was sent for pathological analysis revealing pseudogout. Axial calcium pyrophosphate crystal deposition is rare but reported in the literature and found at the craniocervical junction and skull. Spinal calcium pyrophosphate crystal deposition is rare in the thoracic spine. It is often asymptompatic and can involve the disc or ligaments. This case demonstrates a unique presentation of CPDD.


The uptake of sevoflurane during anaesthesia.
The rate of uptake of sevoflurane during clinical anaesthesia (1.3 MAC) was measured by computer-controlled injection of liquid anaesthetic into a closed breathing system. The cumulative uptake of sevoflurane was 4.8 ml, 7.4 ml, 9.5 ml and 11.5 ml at 30, 60, 90 and 120 min, respectively. The ratio of inspired to end-expired sevoflurane was greater than similar measurements we have made for desflurane in the past, but the absolute rate of sevoflurane uptake was less than the rate of uptake of desflurane in these cases. The rate of uptake was equivalent to 059e-0.32t + 0.039e-0.036t + 0.105e-0.0034t ml.min-1 liquid sevoflurane. Plasma urea and creatinine measured on the first postoperative day were not significantly different from pre-operative values.


Spectroscopic analysis of microplastic contaminants in an urban wastewater treatment plant from Seoul, South Korea.
In this study, a systematic multi-spectroscopic analysis of microplastics (MPs) sampled from a metropolitan area of Seoul was undertaken to elevate understanding of the role of wastewater treatment plants (WWTPs) in eliminating suspended contaminants including MPs before releasing the effluent water into the environment. We analyzed pollutants in influent and effluent samples from a WWTP in Seoul, South Korea. Spectroscopic and microscopic methods were used to analyze MPs. Fourier-transform infrared (FT-IR) spectroscopy in the wavenumber region between 4000 and 715 cm-1 was employed to estimate the abundance of MPs in wastewater. Stereomicroscope images and Nile red staining were used to facilely identify MPs in both influents and effluents to compare the results with those of FT-IR data. Hyperspectral imaging could identify MPs in the influent sample with the reflection method at 400-900 nm. Our preliminary results indicate that the most observed MPs after the wastewater were filtered by a 45 μm stainless steel mesh filter were polyethylene (PE) and polypropylene (PP). The total number of the prevalent MPs in influent samples decreased significantly. Nanostructure particles could be found by field-emission scanning electron microscopy (FE-SEM). Our combined multi-spectroscopic study should be helpful to provide a guideline for the rapid spectroscopic analysis of freshwater in the Han River, Seoul, South Korea.


Kinetics of sodium in rabbit arterial wall: inability of aldosterone to alter extra to intracellular distribution.
Transport rate constants (kij) describing the kinetics of Na exchanges in isolated rabbit aorta wall were determined by a previously established method involving the use of 22Na as a tracer and digital computer simulation without recourse to ancillary chemical measurements of extracellular space. A three compartment model consisting of (i) extracellular, (ii) intracellular and (iii) subcellular spaces (compartments) was found to describe adequately the kinetics of 22Na. Normative values for intercompartmental kij and extra to intracellular Na ratio were established. It appears that the Na extracellular space in rabbit arterial wall is larger than that in dog or rat arterial wall. Surprisingly, at variance with several tissues of different species (dog, rat, mouse and human tissues), aldosterone did not influence the extra to intracellular distribution of Na. The findings are interpreted in the light of results obtained previously by other workers using entirely unrelated methodologies and suggest that species difference is an important factor to consider when studying effects of aldosterone on tissue electrolyte distribution in the rabbit.


Investigation of Chiral Smectic Phases and Conformationally Disordered Crystal Phases of the Liquid Crystalline 3F5FPhH6 Compound Partially Fluorinated at the Terminal Chain and Rigid Core.
Complementary methods are applied to investigate the phase transitions and crystallization kinetics of the liquid crystalline compound denoted as 3F5FPhH6. Two crystal phases are confirmed, and one of them is the conformationally disordered (CONDIS) phase. Complexity of the melt crystallization process is revealed by the analysis with Friedman's isoconversional method. The melt crystallization of 3F5FPhH6 shows different mechanisms depending on temperature, which is explained by the relation between the thermodynamic driving force and the thermal energy of translational degrees of freedom. The studied compound crystallizes even during fast cooling (30 K/min), unlike similar compounds with different fluorosubstitutions of the benzene ring, which form the smectic glass for moderate cooling rates. The tendency to vitrification of the smectic phase decreases apparently with the decreasing stability width of the SmCA* phase and the increasing relaxation time of the collective relaxation process in this phase, at least for homologues differing from 3F5FPhH6 only by the type of fluorosubstitution.


Combination of magnetic targeting with synergistic inhibition of NF-κB and glutathione via micellar drug nanomedicine enhances its anti-tumor efficacy.
Breast cancer is not only one of the most prevalent types of cancer, but also it is a prime cause of death in women aged between 20 and 59. Although chemotherapy is the most common therapy approach, multiple side effects can result from lack of specificity and the use of overdose as safe doses may not completely cure cancer. Therefore, we aimed in this study is to combine the merits of NF-κB inhibiting potential of celastrol (CST) with glutathione inhibitory effect of sulfasalazine (SFZ) which prevents CST inactivation and thus enhances its anti-tumor activity. Inspired by the CD44-mediated tumor targeting effect of the hydrophilic polysaccharide chondroitin sulphate (ChS), we chemically synthesized amphiphilic zein-ChS micelles. While the water insoluble SFZ was chemically coupled to zein, CST was physically entrapped within the hydrophobic zein/SFZ micellar core. Moreover, physical encapsulation of oleic acid-capped SPIONs in the hydrophobic core of micelles enabled both magnetic tumor targeting as well as MRI theranostic capacity. Combining magnetic targeting to with the active targeting effect of ChS resulted in enhanced cellular internalization of the micelles in MCF-7 cancer cells and hence higher cytotoxic effect against MCF-7 and MDA-MB-231 breast cancer cells. In the in vivo experiments, magnetically-targeted micelles (154.4 nm) succeeded in achieving the lowest percentage increase in the tumor volume in tumor bearing mice, the highest percentage of tumor necrosis associated with significant reduction in the levels of TNF-α, Ki-67, NF-κB, VEGF, COX-2 markers compared to non-magnetically targeted micelles-, free drug-treated and positive control groups. Collectively, the developed magnetically targeted micelles pave the way for design of cancer nano-theranostic drug combinations.


Survey on digital dependency, writing by hand, and group learning as learning styles among Japanese medical students: Assessing correlations between various accomplishments.
Although digital learning devices have become increasingly more common in medical education settings, it remains unclear how they influence medical student learning styles and various outcome measures. This study aimed to assess student learning styles, specifically as they relate to digital dependency, writing habits, and group learning practices among current medical students. This questionnaire study was approved by the Research Ethics Committee of Osaka Medical and Pharmaceutical University. We conducted a questionnaire survey of 109 medical students who were 5th year students during the 2021 school year. Medical students were asked about their level of digital dependency, writing by hand, and group learning practices. We also analyzed the correlation between student learning styles and their respective outcomes on several summative evaluations. Of the 109 students targeted, we received responses from 62 (response rate, 56.8%). Among the respondents, digital dependency was 83.4 ± 18.6%, while hand writing ratio 39.8 ± 29.9% and group learning ratio 33.5 ± 30.5%. We also assessed correlations between these learning styles and scores on the CBT, OSCE, CC, and CC Integrative Test. Only writing by hand showed a small positive correlation with CC Integrative Test scores. Our questionnaire survey assessed the rates of digital dependency, writing by hand, and group learning practices, and analyzed the correlations between these learning styles and respective outcomes. Current medical students exhibited high digital dependency which was not correlated with performance outcomes.


Effects of trypsin and plasmin treatment of myelin on the myelin-associated glycoprotein and basic protein.
Human and rat myelin preparations were incubated with varying concentrations of trypsin and plasmin to determine the effects of these proteolytic enzymes on myelin-associated glycoprotein (MAG), basic protein, and other myelin proteins and to compare the effects with those of the neutral protease that was reported to be endogenous in myelin. Basic protein was most susceptible to degradation by both trypsin and plasmin, whereas MAG was relatively resistant to their actions. Under the assay conditions used, the highest concentrations of trypsin and plasmin degraded greater than 80% of the basic protein but less than 30% of the MAG, and lower concentrations caused significant loss of basic protein without appreciably affecting MAG. Neither trypsin nor plasmin caused a specific cleavage of MAG to a derivative of MAG (dMAG) in a manner analogous to the endogenous neutral protease. Thus the endogenous protease appears unique in converting human MAG to dMAG much more rapidly than it degrades basic protein. MAG is slowly degraded along with other proteins when myelin is treated with trypsin or plasmin, but it is less susceptible to their action than is basic protein.


Vasopressin's effects on acquisition and extinction of conditioned avoidance response to smoking.
Lysine-8-vasopressin (LVP) 5 I.U. or NaCl was administered intranasally daily for 5 days in a double blind study to 14 women and 7 men volunteers, 30 minutes prior to aversive conditioning sessions designed to assist them to stop smoking. Subjects were asked to record the number of urges to smoke, the strength of their strongest urge to smoke and the number of cigarettes smoked on a daily basis. Adequate data was obtained from 17 subjects for the Lead-in (pretreatment) week and for the Treatment week. Of these, 10 continued to supply sufficient responses through the sixth week of follow-up. During the week of aversive conditioning those subjects receiving LVP smoked significantly fewer cigarettes than the saline treatment group (p less than 0.01). During the Follow-up period the LVP group had significantly more urges to smoke than the saline group (p less than 0.01). The LVP group also smoked significantly more cigarettes than the saline group 4 weeks (p less than 0.05) and 6 weeks (0.01) after the Treatment week. LVP was associated with a facilitation of the acquisition of the avoidance response to smoking followed by an apparent acceleration of the extinction of the avoidance response compared to saline.


Real-world experience of anti-D immunoglobulin in immune thrombocytopenia.
In developing countries, anti-D has been used in immune thrombocytopenia (ITP) as a cheaper alternative to human immunoglobulin. We aim to analyze the response and safety profile of anti-D in patients with severe ITP. A retrospective study was conducted at a tertiary care hospital in Northern India. Patients received a single intravenous infusion of 75 μg/kg anti-D. In total, 36 patients (20 females) were included in this study. The median duration from ITP diagnosis to anti-D therapy was 235 days (range 1-1613 days). Four (11.1%) patients received anti-D as an upfront treatment. The patients' platelet counts rose significantly by the end of day three and continued to be significantly high until day 30 of receiving anti-D (p ≤ 0.001). The overall response rate (ORR) by day seven was 88.89%. There was no effect of age, sex, duration of disease, prior therapy, and platelet count on the ORR. Patients were followed up for a median duration of 52 days (longest follow-up: 3080 days). Six (6/36, 16.67%) patients continued to be in remission till the last follow-up. The hemoglobin fall was statistically significant on day three and day seven (p < 0.001 and p = 0.001) and got normalized by day 30. We observed equally good ORR in mixed populations and different phases of ITP along with long-term sustained response. The study demonstrates a quick and high response rate along with good safety profile to anti-D in all forms of ITP.


Guinea-pig tracheal epithelium and endothelin.
Removal of the epithelium increased the responsiveness of isolated guinea-pig trachea to the contractile effects of endothelin. This phenomenon was observed in the presence of indomethacin (5 microM), captopril (10 microM), bacitracin (20 micrograms/ml) or leupeptin (50 microM), but was inhibited by phosphoramidon (10 microM). Bacitrain enhanced contraction produced by endothelin. The increased responsiveness of denuded guinea-pig trachea to endothelin may be due to removal of an epithelium-derived phosphoramidon-sensitive peptidase.


Birth weight: nature or nurture?
To investigate the relative role of environmental and genetic factors in the determination of birth weight following ovum donation. Data from 62 cases of ovum donation were used to examine the relative influence of donor and recipient on birth weight. The only discernible factors that significantly influenced birth weight were gestational age and recipient's weight. Donor weight, her own birth weight, and the birth weight of the donor's own children were not significantly correlated with the birth weight of the child following ovum donation. It is concluded that the environment provided by the human mother is more important than her genetic contribution to birth weight.


Comparative study of solid-phase and liquid-phase extraction techniques for isolation of phospholipids from plasma.
A liquid-liquid extraction technique and six solid absorbents, silica gel, octadecyl silica (C18), XAD-2, XAD-4, XAD-7 and XAD-8, were compared as effective tools for extraction of phosphatidylcholine (Ptd C), phosphatidylethanolamine (Ptd E), phosphatidylinositol (Ptd I) and phosphatidylserine (Ptd S) from plasma. Using liquid-liquid extraction the recovery of the four phospholipids was in the order of 60% in organic phase and 20% in the liquid interface. Neither silica gel nor C18 materials significantly adsorbed phospholipids from plasma. Amberlite resins were more selective for removal of phospholipids. A recovery of greater than 85% was obtained for Ptd C, Ptd I and Ptd S when XAD-7 or XAD-8 were used as adsorbents. A recovery of approximately 90% for Ptd E was obtained when XAD-2 or XAD-4 were used as adsorbents. A solvent mixture of isopropanol-acetonitrile (1:1) was found to be the most effective eluent for removal of phospholipids from amberlite polymeric resins. These results suggest that resins could be used as an extracting tool for removal of phospholipids from body fluids.


Effects of head-down tilt on intrapulmonary shunt fraction and oxygenation during one-lung ventilation in the lateral decubitus position.
During one-lung ventilation, surgical positions significantly affect deterioration of oxygenation, and the lateral decubitus position is superior in preventing dangerous hypoxemia compared with the supine position. However, additional head-down tilt causes more compression of the dependent ventilated lung by the abdominal contents and may result in dangerous hypoxemia, as occurs in the supine position. Therefore, we evaluated the effect of head-down tilt on intrapulmonary shunt and oxygenation during one-lung ventilation in the lateral decubitus position. Thirty-four patients requiring one-lung ventilation were randomly allocated to the control group (n = 17) or the head-down tilt group (n = 17). Hemodynamic and respiratory variables were measured 15 minutes after one-lung ventilation in the lateral decubitus position (baseline), 5 and 10 minutes after a 10-degree head-down tilt (T5 and T10, respectively), and 10 minutes after the patient was returned to a horizontal position (T20) in the head-down tilt group. Measurements were done at the same time points in the control group without head-down tilting. In the head-down tilt group, cardiac filling pressures were increased after head-down tilt without any changes in cardiac index. Percent change of shunt to baseline value was significantly increased at T10 and T20 in the head-down tilt group. Percent change of arterial oxygen tension to baseline value was significantly decreased at T5, T10, and T20 in the head-down tilt group, whereas it was decreased only at T20 in the control group. Head-down tilt during one-lung ventilation in the lateral decubitus position caused a significant increase in shunt and a decrease in percent change of arterial oxygen tension, without causing dangerous hypoxemia.


Cyclosporine nephrotoxicity is minimized by adjusting dosage on the basis of drug concentration in blood.
Two immunosuppressive regimens-cyclosporine plus prednisone and azathioprine plus prednisone-were compared in 78 renal transplantation patients (39 in each treatment group) who were successfully managed for more than 15 months. In patients who received cyclosporine, the dosage was adjusted to achieve trough whole blood concentrations of 100 to 250 ng/ml measured by liquid chromatography. A greater number of haplotypes matched in the azathioprine-treated group than in the cyclosporine-treated group (P less than 0.026). Graft survival was similar in patients who received azathioprine (95%) and those given cyclosporine (94%). The azathioprine group had a higher mortality (7%) than the cyclosporine group (2%). In a comparison of the two treatment groups, no statistically significant difference was found in posttransplant renal function, based on either serum creatinine or iothalamate clearance. We conclude that renal toxicity due to cyclosporine can be minimized to statistical nonsignificance by using cyclosporine dosages that provide trough whole blood concentrations in the range of 150 to 250 ng/ml during the first 4 months of therapy and 80 to 200 ng/ml thereafter.


Laparoscopy-assisted vaginal hysterectomy clinical pathway. A multivariate analysis of impact on costs and quality of care.
Numerous studies have demonstrated that a well-designed clinical pathway is an effective means of sustaining quality while controlling costs in the management of certain disease entities. We evaluated the impact that cost and medical quality have on the implementation of a clinical pathway for laparoscopy-assisted vaginal hysterectomy (LAVH). This retrospective study involved a sample of 124 patients who underwent LAVH in a medical center in central Taiwan. Patients were divided into two groups on the basis of whether they received treatment before or after implementation of the LAVH clinical pathway. The preclinical pathway group was comprised of 40 patients who underwent LAVH before clinical pathway implementation (May-December 1997). The clinical pathway group included 84 patients who underwent LAVH after implementation of the clinical pathway (January 1998-March 1999). In order to study the impact of the LAVH clinical pathway, patient characteristics were controlled by multiple linear regression. The results showed a significant reduction in cost, average length of hospital stay, and average duration of surgery and anesthesia (p < 0.01). Dependent nominal variables for clinical indicators like postoperative intravenous fluid and injection of antibiotics 48 h after surgery, and complications were analyzed by a logistic regression model. The results noted better control of antibiotic intravenous injection 48 h after surgery in the clinical pathway group (p = 0.03). The other indicators included delay of operation day, blood transfusion, patient mortality, and patients readmitted within 2 weeks. There was one operation day delay and one readmission within 2 weeks of discharge in the preclinical pathway group. Based on our results, the implementation of a clinical pathway for LAVH contains cost while maintaining quality of care, especially when the medical fees are paid under the case payment system.


Are transcription factors NF-kappaB and AP-1 involved in the ANG II-stimulated production of proinflammatory cytokines induced by LPS in dehydrated rats?
We recently reported an involvement of ANG II and the ANG II type 1 (AT1) receptor in the hepatic expression of IL-1beta induced in dehydrated rats by LPS. Here, we first confirmed that ANG II and AT1 receptors contribute to the LPS-induced increase in the splenic concentration of IL-1beta in dehydrated rats. We then investigated whether ANG II contributes to IL-1 production through a modulating effect on the activation of proinflammatory transcription factors (NF-kappaB and AP-1) that is induced in the dehydrated rat's liver and spleen by intravenous injection of LPS. Surprisingly, LPS markedly increased the hepatic activation of NF-kappaB, an effect that was significantly enhanced (rather than reduced) by pretreatment with an ANG-converting-enzyme (ACE) inhibitor or AT1-receptor antagonist. Furthermore, the same ACE inhibitor and AT1-receptor antagonist each increased the resting NF-kappaB activity in the liver and spleen, although they had no effect on the LPS-induced splenic expression of NF-kappaB. Both hepatic and splenic AP-1 expressions were enhanced by LPS. This response was significantly augmented by pretreatment with the AT1-receptor antagonist (but not with the ACE inhibitor) in the spleen, while in the liver, neither drug had any effect. These results suggest that the endogenous ANG II or AT1 receptor suppresses the activation of hepatic or splenic transcription factors in dehydrated rats given LPS. Our results seem not to support the idea that NF-kappaB and AP-1 play key roles in the ANG II-induced enhancement of the production of proinflammatory cytokines that is induced by LPS in dehydrated rats.


Dysregulation of bacterial proteolytic machinery by a new class of antibiotics.
Here we show that a new class of antibiotics-acyldepsipeptides-has antibacterial activity against Gram-positive bacteria in vitro and in several rodent models of bacterial infection. The acyldepsipeptides are active against isolates that are resistant to antibiotics in clinical application, implying a new target, which we identify as ClpP, the core unit of a major bacterial protease complex. ClpP is usually tightly regulated and strictly requires a member of the family of Clp-ATPases and often further accessory proteins for proteolytic activation. Binding of acyldepsipeptides to ClpP eliminates these safeguards. The acyldepsipeptide-activated ClpP core is capable of proteolytic degradation in the absence of the regulatory Clp-ATPases. Such uncontrolled proteolysis leads to inhibition of bacterial cell division and eventually cell death.


A new bitter diterpenoid from Sarcodon scabrosus.
The new cyathane-type diterpenoid sarcodonin I was isolated from the fruiting bodies of the basidiomycete Sarcodon scabrosus. Its structure was determined on the basis of spectroscopic means, including 2D-NMR (HMBC, HMQC, ROESY, 1H, 1H-COSY).


Structure of the lipopolysaccharide from an Escherichia coli heptose-less mutant. I. Chemical degradations and identification of products.
The structure of lipopolysaccharide from a heptose-less mutant of Escherichia coli K-12 has been investigated. Lipopolysaccharide isolated from 32P-labeled cells was treated with mild alkali to yield two separable components: [OH-LPS]-I (approximately 70%) and [OH-LPS]-II (approximately 30%). Mild acidic treatment of [OH-LPS]-I gave mainly a product which was identified as (4-O-phosphoryl-N-beta-hydroxymyristyl-D-glucosaminyl)-beta(1 leads to 6)-N-beta-hydroxymyristyl-D-glucosamine 1-phosphate (Compound I). Further acidic hydrolysis of both [OH-LPS]-I and [OH-LPS]-II yielded as the main product (4-O-phosphoryl-N-beta-hydroxymyristyl-D-glucosaminyl)-beta(1 leads to 6)-N-beta-hydroxymyristyl-D-glucosamine (Compound II). The structures of the above products were deduced by a combination of compositional analyses, sensitivity to phosphomonoesterase, rates of hydrolysis of the phosphate groups and alkali-catalyzed beta elimination of the phosphate residues following appropriate oxidation of hydroxyl groups. These studies together with work reported in the accompanying papers have led to the identification of two species of lipopolysaccharide in the E. coli strain both of which contain a single glucosamine dissacharide unit but differ in having monosubstituted phosphate or pyrophosphate groups at the glycosidic position. Each species of lipopolysaccharide also appeared to be heterogeneous with respect to the number of esterified fatty acyl groups.


Teasing and social rejection among obese children enrolling in family-based behavioural treatment: effects on psychological adjustment and academic competencies.
The first objective was to determine the prevalence of psychological maladjustment (emotional and behavioural problems), low academic competencies and teasing/social rejection among obese Icelandic children enrolling in a family-based behavioural treatment. A second objective was to explore the degree to which teasing/social rejection specifically contributes to children's psychological adjustment and academic competencies when controlling for other variables, including demographics, children's physical activity, parental depression and life-stress. Participants were 84 obese children (mean body mass index-standard deviation score=3.11, age range=7.52-13.61 years). Height and weight, demographics and measures of children's psychological adjustment, academic competencies, teasing/social rejection and physical activity were collected from children, parents and teachers. Parental depression and life-stress was self-reported. Over half the children exceeded cutoffs indicating concern on at least one measure of behavioural or emotional difficulties. Children endorsed significant levels of teasing/social rejection, with almost half acknowledging they were not popular with same-gender peers. Parent reports of peer problems were even higher, with over 90% of both boys and girls being rated by their parents as having significant peer difficulties. However, rates of low academic competencies as reported by teachers were not different from those of the general population. In regression analyses controlling for other variables, self-reported teasing/social rejection emerged as a significant contributor to explaining both child psychological adjustment and academic competencies. The results indicate that among obese children enrolled in family-based treatment, self-reported teasing/social rejection is quite high and it is associated with poorer psychological adjustment as well as lower academic competencies. Parent reports corroborate the presence of substantial peer difficulties, supporting the need to address peer relations with overweight children both in clinical practice and in public health interventions.


Non-occlusive mesenteric ischemia: etiology, diagnosis, and interventional therapy.
Non-occlusive mesenteric ischemia (NOMI) compromises all forms of mesenteric ischemia with patent mesenteric arteries. It generally affects patients over 50 years of age suffering from myocardial infarction, congestive heart failure, aortic insufficiency, renal or hepatic disease and patients following cardiac surgery. Non-occlusive disease accounts for 20-30% of all cases of acute mesenteric ischemia with a mortality rate of the order of 50%. Acute abdominal pain may be the only early presenting symptom of mesenteric ischemia. Non-invasive imaging modalities, such as CT, MRI, and ultrasound, are able to evaluate the aorta and the origins of splanchnic arteries. Despite the technical evolution of those methods, selective angiography of mesenteric arteries is still the gold standard in diagnosing peripheral splanchnic vessel disease. In early non-occlusive mesenteric ischemia, as opposed to occlusive disease, there is no surgical therapy. It is known that mesenteric vasospasm persists even after correction of the precipitating event. Vasospasm frequently responds to direct intra-arterial vasodilator therapy, which is the only treatment that has been shown to be effective.


Different patterns of hepatocellular carcinoma-related malign thrombosis in 18F-FDG PET/CT.
Tumor thrombus is an intravascular malign tumor extension that may occur in various types of cancer. Hepatocellular carcinomas (HCC) are common causes of malign thrombus. The presence of a malign thrombus due to HCC has a dismal prognosis, which affects treatment choices. We present three cases of tumor thrombi due to advanced HCC detected by 18F-FDG PET/CT.


[Microwave tumor ablation. New devices, new applications?].
The majority of patients with hepatic malignancies are not amenable to surgical resection. In some of these cases minimally invasive ablative therapies are a treatment option. Besides radiofrequency ablation, the most common ablative therapies are cryoablation, laser ablation and microwave ablation. The classic fields of application of microwave ablation are the treatment of malignancies of the liver, kidneys and lungs. Furthermore, cases of treatment of bone tumors and tumors of the adrenal gland have been reported as well as treatment of secondary hypersplenism. The manufacturers of microwave systems pursue different strategies to reach an optimal ablation zone, such as water or gas cooling of the antenna, the simultaneous use of different antennas or an automatic modulation of the microwave energy and frequency. In contrast to other tumor ablation methods microwave ablation causes a direct heating of a tissue volume, thus this method is less vulnerable to the cooling effect of vessels in the ablation zone. Moreover the electric conductivity of the treated tissue does not influence microwave radiation so that microwave ablation has advantages for the treatment of high-resistance organs, such as the lungs or bone. Some publications have shown that microwave ablation causes larger ablation zones in less time in comparison to radiofrequency ablation. Classic indications for microwave ablation are the treatment of malignancies of the liver, lungs and kidneys. Initial technical problems have been solved, so that an increasing significance of the microwave ablation among the ablative therapies is to be expected.


Four cases of chromosome changes detected in course of prenatal diagnosis and probably originating in vitro.
In a series of 1000 prenatal diagnoses, four cases were found with chromosome changes. The probable in vitro origin of these changes was demonstrated by starting several parallel cultured simultaneously and by repeating the amniocenteses and chromosome analyses.


Effects of repeated ayahuasca administration on behaviour and c-Fos expression in male rats exposed to the open field.
Considering the long-lasting effects of ayahuasca on the brain and emotional processing, the objective of this study was to evaluate the behavioural and neurobiological effects of repeated ayahuasca administration in an animal model of exploratory behaviour related to novel-environment anxiety. Male Wistar rats received water, 120, 240, 480 or 3600 mg/kg of resuspended freeze-dried ayahuasca by gavage once a day for 30 days; there was also a non-manipulated homecage group. One hour after the last administration, animals were placed individually in the open field for 20 min. We analysed the weight gain, the behavioural response through a stochastic analysis, and c-Fos immunoreactive levels in the hippocampus, amygdala, pre-frontal and barrel field cortex. Ayahuasca at 120 mg/kg increased ambulation, and at 3600 mg/kg decreased vertical exploration and reduced weight gain. Aya3600 had higher c-Fos expression in regions of the hippocampus and infralimbic cortex than homecage, water or aya120 groups. Water-receiving animals had less c-Fos expression in the anterior basolateral amygdala than others groups. Our results show different behavioural effects of ayahuasca: a stimulant-like effect in small doses, and decreased activity in extreme high-dose, probably due to adverse effects. Higher activation of areas involved in emotional processing and the serotonergic pathway adds to the neurobiological literature on repeated/chronic ingestion of ayahuasca. Our data do not support an anxiolytic effect of repeated ayahuasca related to exploring new anxiogenic-environment but suggest that low ayahuasca doses should be further studied. The absence of severe impairment and behavioural syntax alteration reinforce ayahuasca safety.


A single-cell polony method reveals low levels of infected Prochlorococcus in oligotrophic waters despite high cyanophage abundances.
Long-term stability of picocyanobacteria in the open oceans is maintained by a balance between synchronous division and death on daily timescales. Viruses are considered a major source of microbial mortality, however, current methods to measure infection have significant methodological limitations. Here we describe a method that pairs flow-cytometric sorting with a PCR-based polony technique to simultaneously screen thousands of taxonomically resolved individual cells for intracellular virus DNA, enabling sensitive, high-throughput, and direct quantification of infection by different virus lineages. Under controlled conditions with picocyanobacteria-cyanophage models, the method detected infection throughout the lytic cycle and discriminated between varying infection levels. In North Pacific subtropical surface waters, the method revealed that only a small percentage of Prochlorococcus (0.35-1.6%) were infected, predominantly by T4-like cyanophages, and that infection oscillated 2-fold in phase with the diel cycle. This corresponds to 0.35-4.8% of Prochlorococcus mortality daily. Cyanophages were 2-4-fold more abundant than Prochlorococcus, indicating that most encounters did not result in infection and suggesting infection is mitigated via host resistance, reduced phage infectivity and inefficient adsorption. This method will enable quantification of infection for key microbial taxa across oceanic regimes and will help determine the extent that viruses shape microbial communities and ecosystem level processes.


Selective bilateral blood sampling from the inferior petrosal sinus in Cushing's disease: effects of corticotropin-releasing factor and thyrotropin-releasing hormone on pituitary secretion.
We sought to enhance the sensitivity of selective bilateral blood sampling to determine adrenocorticotropin (ACTH) and prolactin levels in the inferior petrosal sinus (IPS) by administering two stimulatory agents--corticotropin-releasing factor (CRF) and thyrotropin-releasing hormone (TRH). We then determined the ACTH and prolactin levels in the IPS of 10 patients with Cushing's disease. After peripheral administration of both CRF and TRH, ACTH levels were significantly higher on the tumor side in all patients. The prolactin level was significantly higher on the tumor side when CRF or TRH was used to stimulate pituitary secretion. Postsurgical immunohistochemistry studies revealed production of both ACTH and prolactin in tumor cells, explaining the abnormal secretion pattern of the pituitary adenoma. The use of CRF and TRH may therefore improve the reliability of selective blood sampling and tests from the IPS in those cases of Cushing's disease for which noninvasive methods have otherwise failed to clarify the diagnosis.


The efficacy of EBUS-guided transbronchial needle aspiration for molecular testing in lung adenocarcinoma.
The purpose of the study was to assess the efficacy of obtaining adequate cytologic specimens by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for molecular testing of lung adenocarcinomas. This was an institutional review board-approved study of all patients who had undergone EBUS-TBNA from April 2010 through March 2012 for the diagnosis, staging, or both of lung cancer. Patients with a diagnosis of adenocarcinoma were reflexively tested for molecular markers by polymerase chain reaction, sequencing, and fluorescence in situ hybridization (FISH). All procedures were performed with patients under conscious sedation in the bronchoscopy suite. Of 205 patients who underwent EBUS-TBNA, 56 patients (24 male, 32 female) had a diagnosis of adenocarcinoma warranting molecular analysis. Molecular analysis was available for epidermal growth factor receptor (EGFR), Kirsten rat sarcoma (Kras) mutation, and anaplastic lymphoma kinase (ALK) gene rearrangement. The institution's clinical protocol involved initial testing for EGFR mutation with a reflex Kras test if the EGFR test result was negative. ALK FISH molecular testing was completed if both EGFR and Kras test results were negative. A total of 52 of 56 (93%) patients had sufficient cytologic material for complete or partial molecular testing, whereas 46 of 56 (82%) patients had sufficient material for all clinically indicated testing. EGFR, Kras, and ALK analysis yielded positive results in 5 (10%), 10 (25%), and 5 (12%) tested specimens, respectively. No complications were associated with EBUS-TBNA. EBUS-TBNA performed with the patient under moderate sedation can be expected to yield sufficient tissue for sequential molecular analysis in the majority of patients. In an era of targeted therapy for lung adenocarcinomas, EBUS-TBNA is effective in clinical practice for complete diagnosis, staging, and treatment planning in these patients.


The markers of pig heart mitochondrial sub-fractions : I. - The dual location of NADPH-cytochrome c reductase in outer membrane and microsomes.
Evidence is presented about the dual location of NADPH-cytochrome c reductase in mitochondrial outer membranes as well as in microsomes, from pig heart. A high specific activity, was found in both fractions, even after their purification by washing, digitonin treatments, or passages on sucrose gradients. A large fraction of the total activity was associated with both mitochondria and microsomes. Mitochondrial outer membrane differs from microsomes by a low choline phosphotransferase activity and the absence of cytochrome P-450. The properties of mitochondrial and microsomal rotenone-insensitive NADH- and NADPH-cytochrome c reductases were studied. In microsomes, both activities have the same optimum pH (8.5) ; in contrast, in mitochondria they have a different one. The Km-NADPH were always much higher than those for NADH. In mitochondria the Km for NAD(P)H were dependent on cytochrome c concentration. The results show that the rotenone-insensitive NADH- and NADPH-cytochrome c reductases of mitochondria and microsomes have quite different behavior and do not appear to be supported by the same enzyme.


Transplantation of crossed fused ectopic kidneys into a single recipient.
Crossed renal ectopia is a rare (1 in 1000 live births) congenital anomaly in which both renal masses are located on one side of the abdomen and in 90% of cases are fused. Although this condition is not typically associated with underlying renal pathology or symptoms, complex vascular anatomy is commonly encountered. A report of the successful transplantation of crossed fused ectopic kidneys as a single allograft. With careful attention to the complex anatomy presented by this anomaly, the course of the patient's transplantation and postoperative convalescence were uncomplicated and resulted in excellent longterm graft function. We report the first successful transplantation and longterm function of crossed fused ectopic kidneys as a single allograft. Given the shortage of cadaveric renal allografts, patients with this anomalous condition should not be excluded as potential organ donors. Transplant surgeons should have an understanding of this anomaly and its anatomic variants to ensure proper utilization of this limited but valuable resource.


Measurements of diagnostic examination performance and correlation analysis using microvascular leakage, cerebral blood volume, and blood flow derived from 3T dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging in glial tumor grading.
To assess the diagnostic accuracy of microvascular leakage (MVL), cerebral blood volume (CBV) and blood flow (CBF) values derived from dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging (DSC-MR imaging) for grading of cerebral glial tumors, and to estimate the correlation between vascular permeability/perfusion parameters and tumor grades. A prospective study of 79 patients with cerebral glial tumors underwent DSC-MR imaging. Normalized relative CBV (rCBV) and relative CBF (rCBF) from tumoral (rCBVt and rCBFt), peri-enhancing region (rCBVe and rCBFe), and the value in the tumor divided by the value in the peri-enhancing region (rCBVt/e and rCBFt/e), as well as MVL, expressed as the leakage coefficient K(2) were calculated. Hemodynamic variables and tumor grades were analyzed statistically and with Pearson correlations. Receiver operating characteristic (ROC) curve analyses were also performed for each of the variables. The differences in rCBVt and the maximum MVL (MVL(max)) values were statistically significant among all tumor grades. Correlation analysis using Pearson was as follows: rCBVt and tumor grade, r = 0.774; rCBFt and tumor grade, r = 0.417; MVL(max) and tumor grade, r = 0.559; MVL(max) and rCBVt, r = 0.440; MVL(max) and rCBFt, r = 0.192; and rCBVt and rCBFt, r = 0.605. According to ROC analyses for distinguishing tumor grade, rCBVt showed the largest areas under ROC curve (AUC), except for grade III from IV. Both rCBVt and MVL(max) showed good discriminative power in distinguishing all tumor grades. rCBVt correlated strongly with tumor grade; the correlation between MVL(max) and tumor grade was moderate.


A new tool for the assessment of satisfaction with iron chelation therapy (ICT-Sat) for patients with β-thalassemia major.
High satisfaction with iron chelation is a major determinant for adherence to ICT in beta-thalassaemia major (β-TM) patients. In this study, a new tool to assess different domains of satisfaction for available forms of ICT was developed and validated. The impact of patients' satisfaction with ICT has been tested. Items were generated via focus groups and a preliminary version with 24 items (ICT-Sat) with an additional item for treatment preference and a knowledge questionnaire (KQ) was developed. 170 β-TM patients from three Thalassaemia centers in Egypt, aged 2-32 years received three questionnaires to fill in; the new ICT-Sat, a KQ, and a previously validated tool for satisfaction with ICT (SICT) and retested 4-6 weeks later to ensure re-test reliability. Type of chelation, drug related adverse events, compliance with ICT, and serum ferritin level (SF) during the year prior to the study as well as available cardiac T2*data were recorded. One hundred and fifty two β-TM patients completed all questionnaires; median age was 12 years. The final 15 remaining ICT-Sat items, yielding to four domain scores, explained 70.6% of the total variance. The "perceived effectiveness" and "fear and worries" domains of the ICT-Sat correlated significantly with the domains "perceived effectiveness" and "acceptance" of the SICT. Patients treated with oral ICT were more satisfied with perceived effectiveness, and their side effects. A new clinically based ICT-Sat tool was developed and revealed good psychometric characteristics. Adherence to ICT was better correlated with "perceived effectiveness" and SF level.


Decisional conflict and its determinants among patients with cancer undergoing immunotherapy combined with chemotherapy or targeted therapy: a cross-sectional study.
Decisional conflict might occur during shared decision-making (SDM) because immunotherapy is a rather novel treatment option for patients with cancer. To explore the prevalence and severity of physical and psychological symptoms and the effort invested in SDM in relation to decisional conflict among patients with cancer undergoing immunotherapy combined with chemotherapy or targeted therapy. This was a cross-sectional survey study. The SURE version of the Decisional Conflict Scale was used to screen cancer patients' decisional conflict status. Demographic or clinical characteristics, physical symptoms and psychological distress; efforts invested in the SDM process were also assessed as potential factors related to decisional conflict. One hundred seventeen patients surveyed, the prevalence of fatigue (79.5%), sleep disturbance (78.6%), poor appetite (67.5%), and pain (58.1%) symptoms were high and the severity was at moderate levels. The prevalence of pruritus (40.2%), rash (34.2%), dry skin (41.9%), and diarrhea (17.1%) symptoms were low and the severity was at mild levels. 65.8% of patients reported uncertainty, with mild to moderate levels. Furthermore, 97.4% of the patients made some effort in SDM, and the effort level was moderate (mean: 5.56 ± 2.02). 64.1% of patients were certain that immunotherapy was the best option. Age, uncertainty, and effort in the SDM process were major factors related to decisional conflict. We observed that older patients (age: ≥ 65) and those with higher uncertainty levels and less effort in SDM reported higher levels of decisional conflict. Future studies should explore older patients' decisional related needs of immunotherapy. Interventions should be designed to reduce the uncertainty experienced by patients with cancer and enhance their understanding of immunotherapy to enable them to take more effort in the SDM process.


Serial changes of plasma nitrate in the acute phase of Kawasaki disease.
Endogenous nitric oxide (NO) production increases with clinical conditions associated with immune stimulation. In Kawasaki disease (KD), various cytokines play a role in inflammatory reactions in the cardiovascular system. The authors hypothesized that elevated concentrations of nitrate was related to the severity of vasculitis. The aim of the present study was to evaluate serial changes of plasma nitrate concentrations in the acute phase of KD and to consider how NO is related to the inflammatory process of KD and to the coronary artery lesion (CAL). Thirty patients with KD and 20 age-matched healthy controls were enrolled in the present study. Blood samples were obtained weekly for the first and second months. The patients were divided into two groups: one with CAL (n = 11) and another without CAL (n = 19). Plasma nitrate was measured by high-performance liquid chromatography. In both groups, plasma nitrate increased remarkably from the first week to the third week. Peak concentrations of nitrate (mean +/- SD, micro mol/L) in each group were as follows: 56.9 +/- 23.8 in the CAL(+) group and 68.2 +/- 33.8 in the CAL(-) group. Plasma nitrate decreased from the third week to the second month but was still elevated in both groups in comparison with the age-matched healthy controls. There was no correlation between plasma nitrates and white blood cell count or C-reactive protein, respectively (r = 0.013, 0.075). The results suggest that NO production may not be related to the severity of vascular inflammation and that elevated nitrate during the first month of illness may not be associated with a higher risk of CAL.


Prostaglandin E2 in the lung lavage fluid of premature newborns before and after surgical or medical closure of a patent ductus arteriosus.
To analyze the role of prostaglandin E2 in maintaining ductal patency in premature newborns, we measured the PGE2 concentration in the lung lavage fluid of nine patients within 24 h before and 4-8 h after surgical ligation of a patent ductus arteriosus and in two patients before and after closure of the ductus following intravenous indomethacin. The concentration of PGE2 ranged from 240 to 3770 pg/ml (mean 1666 +/- 1256 pg/ml) before operative intervention and show a significant decrease to 0-300 pg/ml (mean 93 +/- 106 pg/ml, P less than 0.001, Student's two-tailed t-test) within a few hours after ligation of the ductus arteriosus. The same significant decrease could be seen in two patients with successful indomethacin therapy (0.25 mg/kg in three doses/day) with concomitant ductus closure. In contrast, when indomethacin was given in a reduced dose (0.1 mg/kg in three doses/day), only a slight effect on PGE2 synthesis could be seen without closure of ductus arteriosus. We suggest that the fall of PGE2 levels in lung lavage fluid reflects the local synthesis in the ductus arteriosus itself and is responsible for the decrease induced by surgical ligation or pharmacological inhibition by indomethacin.


The efficacy of intensive granulocyte and monocyte adsorption apheresis in a patient with Crohn's disease complicated by extensive subcutaneous aseptic neutrophilic abscesses.
Subcutaneous aseptic abscess is one phenotype of neutrophilic dermatitis. We were interested to see if a case of steroid refractory Crohn's disease (CD) complicated by subcutaneous aseptic neutrophilic abscesses responds to intensive granulocyte/monocyte adsorptive apheresis (GMA). The patient was a 21-year-old male with worsening severe CD while on oral prednisolone (30 mg/day). His symptoms included fever, bloody diarrhoea and multiple painful subcutaneous nodules throughout his body. Skin biopsy showed chronic panniculitis with neutrophilic infiltrates. Further, colonoscopy showed oedematous sigmoid colon, while colonic biopsy showed non-caseous granuloma. Because biologics were feared to increase the risk of bacteraemia as the result of germ culture on his pus was not known at the time, we decided to treat this case with GMA. Five GMA sessions with the Adacolumn over 5 consecutive days (daily GMA) were initiated. On admission, his CD activity index (CDAI) was 355, C-reactive protein (CRP) 11.2 mg/dL. After 5 GMA sessions, CDAI decreased to 170, and CRP fell to 5.0 mg/dL, with no fever. GMA was restarted at 2 sessions/week (total 10 sessions). The patient's CDAI fell to <150, and the skin lesions re-epithelialized. In this CD case complicated by subcutaneous aseptic neutrophilic abscesses, GMA appeared to be effective. Our impression is that when biopsy reveals neutrophil infiltrate is a major feature of the lesions, GMA should be considered. As GMA appears to have no safety concerns, a frequent GMA protocol, like daily followed by 2 to 3 times/week should be preferred over the routine weekly GMA.


Developing a reliable and valid competency model for assistant dentists in China.
The shortage of dentists is one of the various medical-resource problems found around the world. More and more countries are improving the provision of oral services by training dental therapists and hygienists. In China, they are called assistant dentists, and they supplement dental services, but thus far, no research has been conducted on the competence of this group. The purpose of this study was to establish a competency model for Chinese assistant dentists. This model can provide a more scientific basis for the education, training, and evaluation of these professionals, as well as provide a reference for the capacity of dental therapists in various countries. We established a system of competency characteristics using theoretical analysis and focus group discussions, after which we established an initial competency model by consulting a Delphi panel of 29 experts. Finally, we collected data from 1389 assistant dentists from 14 provinces in China, and the reliability and validity of the model were confirmed by factor analysis of this data. After three rounds of Delphi panels, the competency model came to include seven ability levels and 50 indicators. In exploratory-factor analysis, three indicators were eliminated, and the questionnaire could explain 68.41 % of total variance. In confirmatory-factor analysis, the established model and data fit well (goodness-of-fit index [GFI] = 0.914, root mean square error of approximation [RMSEA] = 0.047). The results showed that the entire model has good reliability and validity. Our competency model for dental assistants in China includes seven elements. This is consistent with the current health situation in China, and it has distinct Chinese characteristics. Some of our findings, like those reported in other countries with dental therapists, offer ideas for other developing countries.


Cross-cultural adaptation and validation of the Korean version of the Oxford shoulder score.
The Oxford shoulder score (OSS) is being used increasingly and has been adapted cross-culturally in some Western countries. On the other hand, there are few validated translations of the OSS in Asian countries. This study translated and adapted cross-culturally the original OSS to produce a Korean version, and assessed the validity and reliability of the Korean version of the OSS (Korean OSS). One hundred and five patients with shoulder pain caused by degenerative or inflammatory disorders completed the Korean OSS and Korean disability of arm, shoulder and hand (DASH). In addition, the pain score by a visual analog scale (VAS) during activity and at rest, subjective assessment of activities of daily living (ADL), the active range of motion (ROM), and measurements of the abduction strength (strength) were included in the validation process. There were no major linguistic or cultural problems during the forward and backward translations of the MHQ, except for a minor change due to cultural discrepancies in eating such as using a spoon and chopsticks by one dominant hand instead of a knife and fork by two hands. The internal consistency was high (Cronbach's alpha 0.91). The reproducibility test showed no significant difference (Intra-class coefficient 0.95). The construct validity, which was tested by the Pearson correlation coefficient revealed a strong correlation (r > 0.6) between the Korean OSS against subscale of DASH disability/symptom, DASH work and ADL, as well as a moderate correlation (0.3 < r < 0.6) with the DASH sports/music, strength, ROM, pain during activity and pain at rest. The Korean OSS proved to be valid by demonstrating a significant correlation with the patient-based upper extremity questionnaire and clinical assessment. The application and evaluation of the instrument is feasible and understandable among patients in Korea.


Proximal humeral fracture osteosynthesis in Belgium: a retrospective population-based epidemiologic study.
Proximal humeral fractures (PHF) comprise approximately five percent of all fractures and this percentage will continue to increase due to the aging population with accompanying osteoporosis. Most PHF can be treated conservatively; however, in displaced fractures, surgical treatment is recommended. Retrospective analyses of large groups or even populations are important as they can contribute to the needs of the community. The aim of this study was to assess the epidemiology and management of PHF fixation in Belgium based on the most recently available data from the last 5 years. The governmental organization National Institute of Health and Disability Insurance provided a population-based database with all PHF treated surgically or nonoperatively. This database was retrospectively assessed. The data included age, sex, region of residence, year and treatment strategy for every patient. Healthcare expenses were also provided. A total of 62,290 PHF were identified in Belgium between 2014 and 2018. The incidence was 111 per 100,000 persons/year. The highest incidence was observed in females and people older than 80 years. The average proportion of osteosynthesis was calculated at 21%. The Belgian government spent on average more than two million euros each year on PHF treatment. The overall incidence of PHF increased by 12% over the last 5 years. The majority were treated nonoperatively in Belgium.


Comparative study of medial opening-wedge high tibial osteotomy using 2 different implants.
The purpose of this study was to perform a retrospective clinical and radiographic evaluation after opening-wedge high tibial osteotomy (HTO) using a short spacer plate (Aescula; B. Braun Korea, Seoul, South Korea) and rigid long plate (TomoFix plate; Mathys, Bettlach, Switzerland) at follow-up 2 years postoperatively. We performed 94 opening-wedge HTOs with the Aescula plate (group I) and 92 HTOs with the TomoFix plate (group II). Patients underwent clinical and radiographic evaluations preoperatively and at 2 years postoperatively. Clinical evaluations were performed with Knee Society scores. Radiographic analysis included the mechanical tibiofemoral angle (mTFA) and the slope of the tibia angle with preoperative and postoperative full weight-bearing anteroposterior whole-leg views, as well as anteroposterior, lateral, and Merchant views of the knee. We measured the mTFA. In addition, we evaluated the complications in each group. The follow-up period was 2 years. At follow-up 2 years postoperatively, we observed an overall complication rate of 38% in group I and 26% in group II (P = .083). We found plate-related complication rates of 20% in group I and 9% in group II (P = .039). Plate-related complications included loss of correction, fracture of the tibial plateau, screw failure, malunion, and fracture of the lateral cortical bone. The mean mTFA was -6.0° ± 3.2° in group I and -4.6° ± 2.8° in group II preoperatively (P = .262). The mean mTFA was 1.0° ± 3.1° in group I and 1.5° ± 2.3° in group II at the latest follow-up (P = .034). In group I, the mean Knee Society knee score and function score were 60.0 ± 12.9 and 57.9 ± 26.8, respectively, preoperatively. They improved to 92.1 ± 8.1 and 89.0 ± 15.1, respectively, at follow-up (P = .001 and P = .001, respectively). In group II, the mean Knee Society knee score and function score were 57.5 ± 14.8 and 57.4 ± 22.1, respectively, preoperatively. They improved to 95.5 ± 5.4 and 95.0 ± 7.6, respectively, at follow-up (P = .001 and P = .001, respectively). In addition, the mean postoperative knee score and function score in group II were higher than those in group I (P = .001 and P = .001, respectively). We have shown a high plate-related complication rate and a significant loss of correction during a short-term follow-up period (2 years) after opening-wedge HTO using the new short spacer HTO plate compared with the rigid long plate. Level IV, therapeutic case series.