The Decomposition of Shared Environmental Influences on Externalizing Syndromes in the Swedish Population: A Multivariate Study.
Using information from Swedish population registries, we attempt to decompose the shared environment (C) into four subcomponents: close family, family, household, and community. Among pairs differing in their genetic and geographical/household relationships, we examine three externalizing syndromes: drug abuse (DA), criminal behavior (CB), and alcohol use disorders (AUD). The best-fitting common pathway model suggested that total estimates for C were higher for DA (21% for males and 18% for females) than for AUD (16% and 14%) and CB (17% and 10%). Concerning syndrome-specific influences in males, close family effects were stronger for CB and AUD, while community effects were stronger for DA. The two C components in between community experiences and close family experiences (family and household) were estimated to almost entirely derive from the common latent factor. In females, among the four components of C, the community experiences were just slightly above zero, while the C components referred to as the household effect were almost zero. The total close family experiences were similar and most important across syndromes were also divided into common and specific components. For all syndromes, for both males and females, the effects of additive genetic factors were 2-4 times the size of the total effect of the shared environment. Applying standard methods to novel relationships, we expand our understanding of how the shared environment contributes to individual differences in three externalizing syndromes.


[Immunologic reactions with group-specific antigens of group A Streptococcus in rheumatic fever].
The levels of Group A streptococcal antigens, characterized by group specificity, incorporated in the immune complexes, were measured by enzyme immunoassay, and antibodies to group-specific polysaccharide were titered in patients with rheumatic fever of the minimal activity, running a protracted course. A statistically significant rise of these parameters was revealed in rheumatic patients as against normal subjects or patients with chronic tonsillitis with tonsillogenic cardiopathy. The diagnostic informativeness of these methods was found higher than that of antistreptolysin-O determination. The authors make a conclusion that signs of streptococcal infection persist in cases with the minimal activity of the rheumatic process and discuss rational antibiotic therapy of such patients. The described methods are recommended for the diagnosis and differential diagnosis of rheumatic fever of low activity.


Characterization of a vaccinia virus-encoded double-stranded RNA-binding protein that may be involved in inhibition of the double-stranded RNA-dependent protein kinase.
The work described in this article identifies a vaccinia virus-encoded protein that may be involved in inhibition of the interferon-induced, double-stranded RNA-dependent protein kinase. Extracts prepared from vaccinia virus (WR strain)-infected cells contain an inhibitor of this kinase. Inhibition was reduced in extracts from which dsRNA-binding proteins had been removed by preadsorption to poly(rI).poly(rC)-Sepharose, suggesting that a dsRNA-binding protein may be involved in kinase inhibition. A single major virus-specific polypeptide of Mr = 25,000 (p25) bound to the poly(rI).poly(rC)-Sepharose. p25 was synthesized in a coupled in vitro transcription/translation system programmed with vaccinia cores, indicating that it is a vaccinia-encoded protein. Synthesis of p25 was detected at early times, by 2 hr post infection, peaked at 5 hours postinfection, and decreased during the late phase of virus replication. In the presence of cytosine arabinoside p25 synthesis did not decrease at late times postinfection. Kinase inhibitory activity accumulated with similar kinetics to p25, both in the presence and absence of cytosine arabinoside. Kinase inhibitory activity copurified with p25, through gel filtration, and Cibacron blue-affinity chromatography. Removal of p25 by precipitation with antiserum to p25 decreased kinase inhibitory activity in extracts prepared from vaccinia virus-infected cells. These results suggest that p25 may be necessary for the specific kinase inhibitory activity detected in vaccinia virus-infected cells.


Human MUC2 mucin gene is transcriptionally regulated by Cdx homeodomain proteins in gastrointestinal carcinoma cell lines.
In intestinal metaplasia and 30% of gastric carcinomas, MUC2 intestinal mucin and the intestine-specific transcription factors Cdx-1 and Cdx-2 are aberrantly expressed. The involvement of Cdx-1 and Cdx-2 in the intestinal development and their role in transcription of several intestinal genes support the hypothesis that Cdx-1 and/or Cdx-2 play important roles in the aberrant intestinal differentiation program of intestinal metaplasia and gastric carcinoma. To clarify the mechanisms of transcriptional regulation of the MUC2 mucin gene in gastric cells, pGL3 deletion constructs covering 2.6 kb of the human MUC2 promoter were used in transient transfection assays, enabling us to identify a relevant region for MUC2 transcription in all gastric cell lines. To evaluate the role of Cdx-1 and Cdx-2 in MUC2 transcription we performed co-transfection experiments with expression vectors encoding Cdx-1 and Cdx-2. In two of the four gastric carcinoma cell lines and in all colon carcinoma cell lines we observed transactivation of the MUC2 promoter by Cdx-2. Using gel shift assays we identified two Cdx-2 binding sites at -177/-171 and -191/-187. Only simultaneous mutation of the two sites resulted in inhibition of Cdx-2-mediated transactivation of MUC2 promoter, implying that both Cdx-2 sites are active. Finally, stable expression of Cdx-2 in a gastric cell line initially not expressing Cdx-2, led to induction of MUC2 expression. In conclusion, this work demonstrates that Cdx-2 activates the expression of MUC2 mucin gene in gastric cells, inducing an intestinal transdifferentiation phenotype that parallels what is observed both in intestinal metaplasia and some gastric carcinomas.


[Single photon emission computed tomography (SPECT) for the diagnosis of depressive disorders, neurotic and eating disorders].
The aim of the study was to estimate usefulness of the single photon emission computed tomography (SPECT) for the diagnostics of the depressive disorders, neurotic and eating disorders, and detect the organic factors and correlation between cerebral hypoperfusion and results of Benton's and Bender's tests. Study of 43 patients (33 women and 10 men) aged 16--59 years (SD+38, 65 +/- 11, 62) which were examined with single photon emission computed tomography (SPECT) and Benton's and Bender's tests during their treatment in the 1st Department of Psychiatry, Medical University in Gdańsk in the years 2000 to 2003. 30 patients were diagnosed with depression (first depressive episodes--8, recurrent depressive disorders--9, organic depression--13), 8--neurotic disorders and 5--eating disorders. SPECT in 38 (88,37%) cases showed hypoperfusion mostly on the left side and in the frontal region. Hypoperfusion in the recurrent depressive disorders was considerably greater (nearly significant) in comparison with the first depressive episodes. The correlation between hypoperfusion and CNS impairment examined with Benton's and Bender's tests was observed. The correlation coefficient of was 0.6845.


MRI reliability in pediatric abdominal lymph node metastases?
Although positron emission tomography-computed tomography (PET-CT) is an effective imaging method used in the detection of lymph node metastases, repeated imaging increases X-ray exposure, especially in pediatric patients. Magnetic resonance imaging (MRI) may detect abdominal lymph nodes and provide subtle anatomic detail, and functional information without radiation. To evaluate the reliability of MRI in detecting lymph node metastases in pediatric abdominal malignancies and to determine whether X-ray dose can be reduced by comparing its effectiveness with PET-CT. Patients aged <18 years, diagnosed with abdominal malignant solid lesions between January 2015 and 2022 were included in this retrospective single-center study. A total of 14 A total of 14 different anatomic locations were defined for lymph nodes in MRI and PET-CT examinations. Cohen's kappa test was used to evaluate the consistency between PET-CT and MRI. P < 0.05 was considered statistically significant. In total, 25 patients (18 [72%] girls, 7 [28%] boys; mean age = 9.32 ± 16.9 years; age range = 1-18 years) with abdominal solid malignant tumors were included. The reliability of MRI and inter-observer reliability differed depending on the location of the lymph nodes. The reliability was almost perfect for the internal iliac (k = 0.915), porta hepatis, and aortocaval lymph node stations, while fair reliability was observed for the mesenteric lymph nodes (k = 0.525). The results showed that MRI was as reliable as PET-CT in detecting some intra-abdominal metastatic lymph nodes, while its reliability was lower in some lymph node stations.


Processing of human cathepsin G after transfection to the rat basophilic/mast cell tumor line RBL.
The azurophil granules of neutrophil granulocytes contain neutral proteases such as leukocyte elastase and cathepsin G. These are synthesized as inactive precursors, but following proteolytic processing, they are stored in granules as active enzymes. We describe the establishment of a transgenic cellular model for expression of the human myeloid serine protease cathepsin G. The cDNA for preprocathepsin G was stably expressed in the rat basophilic/mast cell line RBL-1 and the translation product was characterized by use of biosynthetic labeling followed by immunoprecipitation, SDS-polyacrylamide gel electrophoresis, and fluorography. Conversion into complex form of an asparagine-linked carbohydrate unit of approximately 3.5 kDa was shown, as judged by the products obtained upon treatment with endoglycosidase H and N-glycanase. Proteolytic processing of 32.5-kDa procathepsin G into a 31-kDa form, within 1-2 h after synthesis, was demonstrated by pulse-chase experiments. Further processing into a 30-kDa form also occurred to a minor extent. The processed forms were enzymatically active, as judged by affinity for the serine protease inhibitors diisopropylfluorophosphate and aprotinin. Translocation of processed forms of cathepsin G to high density fractions, indicating targeting of the protease to granules, was demonstrated by subcellular fractionation. The weak base NH4Cl was shown to delay the processing and enzymatic activation of cathepsin G, whereas the monovalent ionophore monensin completely inhibited both events. Our data demonstrate that human cathepsin G transfected to rat RBL-1 cells, is proteolytically processed into enzymatically active forms and that subcellular transfer to granular organelles occurs. As the processing of transgenic human cathepsin G corresponds to that of endogenous protease of myeloid cells, the model should provide new unique possibilities to further characterize the activation and granular targeting of myeloid serine proteases.


Preliminary findings of a novel measure of driving behaviors in Veterans with comorbid TBI and PTSD.
Veterans of the military operations in Iraq and Afghanistan are at an elevated risk of driving-related accidents and fatalities compared with civilians. Combat exposure, military driving training, risk-seeking, traumatic brain injury (TBI), and posttraumatic stress disorder (PTSD) are all factors associated with driving-related risk. However, few empirical studies have observed driving patterns in this population, and the influence of these contributing factors remains unclear. This study utilized a novel self-report measure to assess driving behaviors, subjective driving-related anxiety, and the emotional experiences of military Veterans who have returned to civilian driving. This questionnaire was completed by 23 combat Veterans diagnosed with comorbid TBI and PTSD and 10 nondisabled combat Veterans. Drivers with TBI and PTSD reported more frequent high-risk driving behaviors and higher levels of anxiety while driving in certain situations than nondisabled combat Veterans. These preliminary findings highlight the importance of studying on-the-road situations and cues that produce anxiety in Veterans, particularly those with TBI and PTSD. A greater understanding of driving-related anxiety is needed to inform targeted and effective interventions for unsafe driving in Veterans.


[Comparative analysis of some factors in tooth color matching].
Recently (nowadays) to achieve a natural looking restoration is an ever increasing demand from the patients and also from the doctor side. To select the right color of the restoration matching the remaining natural teeth is always a challenging task. A clinical study was performed at the University of Debrecen Faculty of Dentristry with the help of dental students using two different shade guides. The study tested the influence of gender and knowledge of color science on shade matching. 78 students were asked to find the right matching color of the same upper canine to two different shade guides (Vitapan Classic and Vita 3D-Master) under standard condition. After informing the student about the basic principles of color the matching procedure was repeated. Results were analyzed statistically. In our study we found that gender does not influence the color choice. Matching accuracy is not increased by better knowledge of colors. We can conclude that significantly less students matched the proper color with Vitapan Classic shade guide after information of the property of colors without training the shade selection. Within the limitation of the study design it was concluded that not more students selected the proper color even after giving them information about colors, instructions about shade selections. For the same one canine several color were selected by the participants (6 types with Vitapan Classic and 19 types with Vita 3D-Master) which conformed that visual determination is not a reliably consistent way of the tooth shade selection. The Vita Company 1990s developed 3D-Master shade guide is not widely used, although we found the repeatability is more than 70%.


An update on the epidemiology of ANCA-associated vasculitis.
ANCA-associated vasculitis (AAV) includes granulomatosis with polyangiitis, microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis. Epidemiological studies in AAV are important in understanding possible aetiologic mechanisms and facilitating healthcare planning. However, epidemiological studies present a number of challenges including clear definition of cases differentiated from other clinical disorders, and identification of cases due to the rarity of AAV. The aim of this review is to summarize different aspects on the epidemiology of ANCA-associated vasculitis from different geographical areas throughout the world. During the past three decades, development of classification criteria worldwide, including the ACR classification of 1990, the Chapel Hill consensus definitions updated in 2012 and the EMA algorithm has facilitated epidemiology studies in AAV. The available epidemiological studies reported in AAV suggest that incidence and prevalence may have increased over the past 30 years. Possible explanations for this increase may be a genuine increase in incidence, the evolution of classification criteria and the definition, and availability and wider use of ANCA serology to aid diagnosis, and greater physician awareness through education. The age-specific incidence for the whole group of AAV showed a clear increase with age. However, there has been a clear shift in the peak age at onset towards a higher age during the last 20-30 years. In addition, variation in incidence of AAV between men and women has been clearly evident in a number of epidemiological studies.


Opportunities for improving post-hospital home medication management among older adults.
Effective post-hospital home medication management among older adults is a convoluted, error-prone process. Older adults, whose complex medication regimens are often changed at hospital discharge, are susceptible to medication-related problems (e.g. Adverse Drug Events or ADEs) as they resume responsibility for managing their medications at home. Human error theory frames the discussion of multi-faceted, interacting factors including care system functions, like discharge medication teaching that contribute to post-hospital ADEs. The taxonomy and causes of post-hospital ADEs and related risk factors are reviewed, as we describe in high-risk older adults a population that may benefit from targeted interventions. Potential solutions and future research possibilities highlight the importance of interdisciplinary teams, involvement of clinical pharmacists, use of transitional care models, and improved use of informational technologies.


Theoretical considerations of the role of antigen structure in B cell activation.
Thymus-independent antigens generally are polymeric molecules with repeating arrays of antigenic determinants. Immunological studies of the activity of haptenated thymus-independent antigens have shown that small changes in hapten density can transform a polymeric antigen from nonimmunogenic to immunogenic, and from immunogenic to tolerogenic. In this paper we compute the equilibrium configuration of a linear flexible, haptenated polymer absorbed to a B cell surface, and correlate configurational features of the molecule with its immunological functioning. A polymeric molecule bound to a cell generally will not lie entirely on the surface; rather there will be sections that form loops extending into solution, separated by tightly bound sections, or trains. Trains link antibody receptors on the B cell surface in a fashion that restricts their mobility. Thus trains cause restrictive cross-linking. Our computations show that there is a critical hapten density below which the polymer does not bind to the surface. At hapten densities slightly above the critical density, the polymer binds weakly to the surface with a configuration dominated by a few, rather long loops. These loops cross-link receptors, but do so without bringing the cross-linked receptors into close proximity and without substantially restricting their motion. Long loops thus cause unrestrictive cross-linking. As the hapten density increases, the average loop length decreases and the average train length increases. Thus cross-linking becomes restrictive. In this density range, immune stimulation is observed. At high hapten densities long trains form, separated by few, very short loops and almost all receptors are cross-linked. Consequently cross-linking may be overly restrictive, freezing receptors into place and generating an abundance of cross-linking or other signals that induce a state of immunological tolerance.


Effect of a mixture of iprobenfos and malathion on the development of malathion resistance in the mosquito Culex pipiens pallens Coq.
A malathion-resistant (RM) strain of Culex pipiens pallens Coq was obtained by successively selecting a field population with malathion in the laboratory. The synergistic effect of iprobenfos on malathion toxicity and alpha-naphthyl acetate (alpha-NA) esterase assay revealed that malathion resistance in the RM strain was associated with increased alpha-NA esterase activity and the synergism was mainly due to the inhibition by iprobenfos of this activity. There was no difference in alpha-NA esterase activity between the larvae and female adults in the susceptible (S) strain, but the activity in the adults was 13-fold higher than in the larvae of the RM strain. To understand the effect of the application of a mixture of iprobenfos and malathion on the evolution of malathion resistance, an artificial strain (Syn) was generated by mixing the RM and S strains with 0.1 frequency of the malathion-resistant individuals. The offspring of the Syn strain were divided into two sub-strains, Rm and Rm+ibp, which were successively treated with, respectively, malathion alone and malathion + iprobenfos (1:2) at LC70. In the mixture, the fungicide iprobenfos acted as a synergist of malathion. After treatment for 10 generations, the resistance level to malathion was 317.4-fold for the Rm sub-strain, whereas for the Rm+ibp sub-strain it was only 38.9-fold, compared with the Syn strain. Similar results were obtained by measurement of alpha-NA esterase activity from both larvae and female adults. The alpha-NA esterase activities in larvae and female adults at F10 generation were 2.6- and 10.9-fold from the Rm+ibp sub-strain and 5.7- and 98.5-fold from the Rm sub-strain, respectively, compared with the Syn strain. The above results suggested that iprobenfos, although it cannot completely stop or prevent the onset of malathion resistance, could dramatically delay its evolution.


Nasopharyngeal penicillin-resistant Streptococcus pneumoniae strains among young children in Japan.
A rapid increase of penicillin resistance in Streptococcus pneumoniae has recently been reported in most areas of the world. Penicillin-resistant S. pneumoniae and other resistant bacteria are the principal causes of recurrent acute otitis media (AOM). Penicillin-resistant S. pneumoniae was examined so that we could investigate the bacteriologic and clinical interpretations of nasopharyngeal flora from healthy children. We obtained nasopharyngeal swab specimens from healthy children attending a day care center and from children attending a public health examination in Kanazawa, Japan. We also obtained clinical specimens from children with AOM who visited the Kanazawa University Hospital and 4 other hospitals in Ishikawa Prefecture in Japan. The chief bacteria from the children were S. pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Penicillin-resistant S. pneumoniae was identified in 75% of children attending a day care center. On the other hand, S. pneumoniae was identified in 37% of children who were not attending day care. Of the children with AOM, penicillin-resistant S. pneumoniae was identified in 77%. Our results suggest that there is a strong relationship between day care attendance and nasopharyngeal carriage of S. pneumoniae. The carriage rate of penicillin-resistant S. pneumoniae in healthy children in day care centers was very high and similar to the carriage rate of young patients with AOM in Japan.


Demyelination during anti-TNFα therapy for ankylosing spondylitis.
A 34-year-old ankylosing spondylitis (AS) patient on etanercept for 30 months presented to neurologists with paresthesia of his hands and feet. Magnetic resonance imaging (MRI) scans showed multifocal hyperintense lesions. Symptoms did not improve on stopping the anti-tumor necrosis factor (TNF) agent. Few cases of demyelinating disease occurring after more than 2 years of treatment with anti-TNF agents have been reported in patients with AS. Opthalmologists, internists, neurologists, and rheumatologists need to be aware of these adverse events, as patients may present to any of these specialties many years after treatment.


Ephrin-A/EphA specific co-adaptation as a novel mechanism in topographic axon guidance.
Genetic hardwiring during brain development provides computational architectures for innate neuronal processing. Thus, the paradigmatic chick retinotectal projection, due to its neighborhood preserving, topographic organization, establishes millions of parallel channels for incremental visual field analysis. Retinal axons receive targeting information from quantitative guidance cue gradients. Surprisingly, novel adaptation assays demonstrate that retinal growth cones robustly adapt towards ephrin-A/EphA forward and reverse signals, which provide the major mapping cues. Computational modeling suggests that topographic accuracy and adaptability, though seemingly incompatible, could be reconciled by a novel mechanism of coupled adaptation of signaling channels. Experimentally, we find such 'co-adaptation' in retinal growth cones specifically for ephrin-A/EphA signaling. Co-adaptation involves trafficking of unliganded sensors between the surface membrane and recycling endosomes, and is presumably triggered by changes in the lipid composition of membrane microdomains. We propose that co-adaptative desensitization eventually relies on guidance sensor translocation into cis-signaling endosomes to outbalance repulsive trans-signaling.


Low-dose oxaliplatin enhances the antitumor efficacy of paclitaxel in human gastric cancer cell lines.
The enhanced antitumor effect of paclitaxel when used with oxaliplatin in gastric cancer is reported, however the underlying biological mechanism is unknown. We tested the cytotoxic activity, apoptosis, and mitotic catastrophe of paclitaxel and oxaliplatin in MKN-28 and MKN-45 gastric cancer cell lines. The modulation of survivin expression was determined by Western blotting. WST-1 assay indicated that paclitaxel plus oxaliplatin showed better cytotoxicity than paclitaxel alone, even when low concentrations of oxaliplatin were used. Flow cytometry analysis revealed significantly greater increases in apoptotic cells after treatment with paclitaxel followed by low-dose oxaliplatin (1 microM) than after any single-reagent regimen in the MKN-45 cell line. In MKN-28, a difference existed only between combination treatment and oxaliplatin treatment. Morphologic examination showed that the cells undergoing mitotic catastrophe were highest in the combination groups in the both cell lines. Downregulation of survivin expression was found by Western blotting with treatment by paclitaxel, oxaliplatin, or their combination. Our findings suggest that the mechanism of enhanced cytotoxicity might be through enhanced mitotic catastrophe and apoptosis, which is possibly due to chemotherapy-induced downregulation of surviving. The combination of paclitaxel and low-dose oxaliplatin should be incorporated into the design of a clinical trial.


Efficacy and safety of autologous peripheral blood stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia: A study protocol for a multicenter exploratory prospective study (Auto-Ph17 study).
The prognosis of Philadelphia chromosome positive acute lymphoblastic leukemia (Ph + ALL) has been dramatically improved since the introduction of tyrosine kinase inhibitors (TKIs). Although allogeneic hematopoietic cell transplantation (allo-HCT) is a major treatment option, the role of autologous peripheral blood stem cell transplantation (auto-PBSCT) has been reconsidered, especially in patients who achieved early molecular remission. This is a multicenter exploratory study for Ph + ALL patients aged between 55 and 70 years who achieved complete molecular remission within 3 cycles of chemotherapy. The target sample size is 5, and the registration period is 2 years. The primary endpoint is Day100- mortality after transplantation, and the secondary endpoints are survival, relapse rate, nonrelapse mortality, and adverse events.This study is divided into 3 phases: peripheral blood stem cell harvest, transplantation, and maintenance. Chemomobilization is performed using a combination of cyclophosphamide (CPM), doxorubicin, vincristine (VCR), and prednisolone (PSL). As a preparative regimen, the LEED regimen is used, which consists of melphalan, CPM, etoposide, and dexamethasone. Twelve cycles of maintenance therapy using a combination of VCR, PSL, and dasatinib are performed.In association with relapse, the minimal residual disease (MRD) of BCR-ABL chimeric gene and T-cell subsets are analyzed both before and after auto-PBSCT. The protocol was approved by the institutional review board of Nagoya University Hospital and all the participating hospitals. Written informed consent was obtained from all patients before registration, in accordance with the Declaration of Helsinki. Results of the study will be disseminated via publications in peer-reviewed journals. Trial registration number UMIN000026445.


Comparison of Contrast-Enhanced Tomographic 3-D Ultrasound Against Rotational Angiography Imaging Immediately After Endovascular Aneurysm Repair.
This proof of principle study assesses the utility of contrast-enhance ultrasound (CEUS) and contrast-enhanced tomographic 3-D ultrasound (CEtUS), as an intra-procedural imaging tool after endovascular-aneurysm repair (EVAR), compared with rotational angiography. A total of 20 consecutive patients undergoing infra-renal EVAR underwent immediate post-deployment rotational angiography, followed by CEUS and CEtUS scans. Outcomes were presence of endoleak, renal artery patency and endograft deformity. CEUS and CEtUS detected 12 endoleaks, 8 of which were not detected by rotational angiography. CEUS and CEtUS classify 7 or 8 type IIb endoleaks not detected by rotational angiography. CEUS/CEtUS could not identify 12 and 13 renal arteries, respectively, detected by rotational angiography. Rotational angiography and CEtUS both identified 1 endograft limb deformity, corrected immediately. CEUS and CEtUS are more sensitive to type II endoleak than rotational angiography, although there is a lower detection of renal arteries. CEUS or CEtUS has the utility for immediate post-EVAR endoleak detection where reduction of contrast agent is indicated.


Hysterectomy: a historical perspective.
In the relatively long history of man, surgery has been a comparatively recent development; the abdomen was first deliberately opened to remove an ovarian cyst by Ephraim McDowell in Kentucky in 1809. The first abdominal hysterectomy was performed by Charles Clay in Manchester, England in 1843; unfortunately the diagnosis was wrong and the patient died in the immediate post-operative period. The following year, Charles Clay was almost the first to claim a surviving patient, however she died post-operatively and it was not until 1853 that Ellis Burnham from Lowell, Massachusetts achieved the first successful abdominal hysterectomy although again the diagnosis was wrong. Vaginal hysterectomy dates back to ancient times. The procedure was performed by Soranus of Ephesus 120 years after the birth of Christ, and the many reports of its use in the middle ages were nearly always for the extirpation of an inverted uterus and the patients rarely survived. The early hysterectomies were fraught with hazard and the patients usually died of haemorrhage, peritonitis, and exhaustion. Early procedures were performed without anaesthesia with a mortality of about 70%, mainly due to sepsis from leaving a long ligature to encourage the drainage of pus. Thomas Keith from Scotland realized the danger of this practice and merely cauterized the cervical stump and allowed it to fall internally, thereby bringing the mortality down to about 8%. Hysterectomy became safer with the introduction of anaesthesia, antibiotics and antisepsis, blood transfusions and intravenous therapy. During the 1930s, Richardson introduced the total abdominal hysterectomy to avoid serosanguineous discharge from the cervical remnant and the risk of cervical carcinoma developing in the stump. Apart from this innovation, and the transverse incision introduced by Johanns Pfannenstiel in the 1920s, there was little advance in hysterectomy techniques until the advent of endoscopic surgery and the performance of the first laparoscopic hysterectomy by Harry Reich in Kingston, Pennsylvania in 1988. The refinement and increasing safety of laparoscopic hysterectomy suggests that it will be used increasingly in the future, although developments in pharmacology and photodynamic therapy and interventional radiology may reduce the traditional indications for the operation.


Wavelet-improved Score-based Generative Model for Medical Imaging.
The score-based generative model (SGM) has demonstrated remarkable performance in addressing challenging under-determined inverse problems in medical imaging. However, acquiring high-quality training datasets for these models remains a formidable task, especially in medical image reconstructions. Prevalent noise perturbations or artifacts in low-dose Computed Tomography (CT) or under-sampled Magnetic Resonance Imaging (MRI) hinder the accurate estimation of data distribution gradients, thereby compromising the overall performance of SGMs when trained with these data. To alleviate this issue, we propose a wavelet-improved denoising technique to cooperate with the SGMs, ensuring effective and stable training. Specifically, the proposed method integrates a wavelet sub-network and the standard SGM sub-network into a unified framework, effectively alleviating inaccurate distribution of the data distribution gradient and enhancing the overall stability. The mutual feedback mechanism between the wavelet sub-network and the SGM sub-network empowers the neural network to learn accurate scores even when handling noisy samples. This combination results in a framework that exhibits superior stability during the learning process, leading to the generation of more precise and reliable reconstructed images. During the reconstruction process, we further enhance the robustness and quality of the reconstructed images by incorporating regularization constraint. Our experiments, which encompass various scenarios of low-dose and sparse-view CT, as well as MRI with varying under-sampling rates and masks, demonstrate the effectiveness of the proposed method by significantly enhanced the quality of the reconstructed images. Especially, our method with noisy training samples achieves comparable results to those obtained using clean data. Our code at https://zenodo.org/record/8266123.


Spinal cord compression of dual etiology, multiple myeloma and spinal tuberculosis.
Spinal cord compression as an initial manifestation of multiple myeloma is a well-known phenomenon. We report for the first time a patient with spinal cord compression of dual etiology, multiple myeloma and spinal tuberculosis, treated successfully by local radiotherapy, chemotherapy and an antituberculous regimen.


Experimental manipulation of cerebral cortical areas in primates.
The developmental mechanisms underlying the subdivision of the neocortex into structurally and functionally distinct areas is central to our understanding of the development of human cognitive capacity and the pathogenesis of congenital disorders of higher brain functions. The protomap hypothesis suggests how the cytoarchitectonic pattern of the cerebral cortex may be generated by a combination of intrinsic and extrinsic influences during embryonic development. Although little is known about the genetic and molecular mechanisms underlying this individual and species-specific diversity of cellular and synaptic architecture, experimental manipulation of development in the primate embryo provides a glimpse into the cascade of cellular events involved in the control of cell numbers, specification of neuronal phenotypes, their apportions into cytoarchitectonic areas, and establishment of area-specific synaptic circuitry.


The contract in medical partnership.
You may spend more time with your partner than with your wife; if you wish to have and to hold from this day forward then read the partnership contract carefully and understand its implications. A review of the main points and pitfalls is given to help the practising doctor draw up and check a contract.


Early life PM2.5 exposure, childhood cognitive ability and mortality between age 11 and 86: A record-linkage life-course study from Scotland.
Living in areas with high air pollution concentrations is associated with all-cause and cause-specific mortality. Exposure in sensitive developmental periods might be long-lasting but studies with very long follow-up are rare, and mediating pathways between early life exposure and life-course mortality are not fully understood. Data were drawn from the Scottish Longitudinal Study Birth Cohort of 1936, a representative record-linkage study comprising 5% of the Scottish population born in 1936. Participants had valid age 11 cognitive ability test scores along with linked mortality data until age 86. Fine particle (PM2.5) concentrations estimated with the EMEP4UK atmospheric chemistry transport model were linked to participants' residential address derived from the National Identity Register in 1939 (age 3). Confounder-adjusted Cox regression estimated associations between PM2.5 and mortality; regression-based causal mediation analysis explored mediation through childhood cognitive ability. The final sample consisted of 2734 individuals with 1608 deaths registered during the 1,833,517 person-months at risk follow-up time. Higher early life PM2.5 exposure increased the risk of all-cause mortality (HR = 1.03, 95% CI: 1.01-1.04 per 10 μg m-3 increment), associations were stronger for mortality between age 65 and 86. PM2.5 increased the risk of cancer-related mortality (HR = 1.05, 95% CI: 1.02-1.08), especially for lung cancer among females (HR = 1.11, 95% CI: 1.02-1.21), but not for cardiovascular and respiratory diseases. Higher PM2.5 in early life (≥50 μg m-3) was associated with lower childhood cognitive ability, which, in turn, increased the risk of all-cause mortality and mediated 25% of the total associations. In our life-course study with 75-year of continuous mortality records, we found that exposure to air pollution in early life was associated with higher mortality in late adulthood, and that childhood cognitive ability partly mediated this relationship. Findings suggest that past air pollution concentrations will likely impact health and longevity for decades to come.


Evaluation of Quinone Outside and Succinate Dehydrogenase Inhibitors for Effectiveness Against Eastern Filbert Blight of Hazelnut.
Most of the hazelnut production in Oregon, a value of $130 million in 2014, was based on eastern filbert blight (EFB) susceptible cultivars. On these cultivars, EFB management involves, among other tactics, fungicide treatment during bud break and early shoot growth. Many active ingredients have been shown to be effective against EFB. This report summarizes the evaluation of quinone outside (QoI, FRAC group 11) and succinate dehydrogenase (SDHI, FRAC group 7) inhibitors alone and in combination with each other or with demethylation-inhibiting (DMI, FRAC group 3) fungicides for management of EFB. Based on a meta-analysis, picoxystrobin, pyraclostrobin, or trifloxystrobin alone resulted in significant control over nontreated trees ranging between 64 and 74%. Fluoxastrobin was not as effective as other QoI fungicides with an average of 44% control and high variability. SDHI fungicides as a group were less useful for management of EFB with boscalid, fluopyram, and penthiopyrad ineffective while fluxapyroxad averaged 83% control against EFB. Prepackaged mixes of QoI materials with either SDHI or DMI fungicides were also significantly effective against EFB. Use of QoI fungicides and the SDHI material fluxapyroxad offers added flexibility and complexity within EFB management programs. Growers can incorporate any of five different modes of action in EFB management programs including FRAC groups M1, M5, 3, 7, and 11.


Computational Study of Glycerol Binding within the Active Site of Coenzyme B12-Dependent Diol Dehydratase.
Molecular dynamics (MD) simulations have been employed for the first time to gain insight into the geometry of glycerol (GOL) bound within the active site of B12-dependent diol dehydratase (B12-dDDH). A peculiar feature of the B12-dDDH enzyme is that it undergoes suicidal inactivation by the substrate glycerol. To fully understand the inactivation mechanism, it is crucial to identify all possible interactions between GOL and the surrounding amino acid residues in the enzyme-substrate complex. Particularly important is the orientation of the C3-OH group in GOL since the presence of this OH group is the only difference between GOL and propanediol (PDO), a substrate for B12-dDDH that does not induce suicidal inactivation. The MD simulations indicate that glycerol can adopt two conformations that differ with respect to the orientation of the C3-OH group; in one conformer, the C3-OH group is oriented toward Ser301 (C3-OH···Ser301), and in the other toward Asp335 (C3-OH···Asp335). Although the former configuration is consistent with the crystal structure of B12-dDDH crystallized with cyanocobalamin (CNCbl) as the cofactor, MD simulations of this system suggest a substantial predominance of the latter conformer. A similar result with an even higher preference for the latter conformer is obtained for B12-dDDH with 5'-deoxyadenosylcobalamin (AdoCbl) as a cofactor. Employing QM/MM calculations it is found that the energy difference between the two conformers of GOL is very small in CNCbl B12-dDDH, where the slightly preferred conformer is C3-OH···Ser301. However, in AdoCbl B12-dDDH, this energy difference is higher, implying that GOL exists predominantly as the C3-OH···Asp335 conformer. These findings offer a new perspective for investigations of substrate-induced inactivation of the B12-dDDH enzyme.


A new minor dimmeric ester from seeds of Cassia fistula L. (Leguminosae).
Bioactivity-guided fractionation of n-hexane phase from MeOH extract of the seeds of Cassia fistula L. (Leguminosae) yielded two bioactive substances against Cladosporium cladosporioides and C. sphaerospermum. After spectroscopic analysis, these compounds were characterised as the known benzyl 2-hydroxy-3,6-dimethoxybenzoate and its dimer dibenzyl 2,2'-dihydroxy-3,6,3″,6″-tetramethoxy-biphenyl-1,1'-dicarboxylate, which showed a new structural arrangement.


The effect of 3-aminobenzamide, an inhibitor of poly-ADP-ribose polymerase, on ischemia/reperfusion damage in rat retina.
Excitotoxic amino acids, such as glutamate, may play an important role in retinal ischemia/reperfusion damage. In central neurons, excitotoxicity may be mediated by nitric oxide synthase (NOS) causing DNA damage via nitric oxide (NO). The nicked DNA activates poly-adenosine diphosphate (ADP)-ribose polymerase (PARP) and may deplete intracellular ATP resulting in cell death. PARP may also be involved in apoptosis. We used 3-aminobenzamide (3-ABA), a PARP inhibitor, to examine the possible involvement of PARP in a rat model of retinal ischemia. Retinal ischemia was induced by elevating the intraocular pressure (IOP) through the insertion of a needle into the anterior chamber of a rat eye. IOP was raised to 110 mm Hg for 60 minutes. Animals were given intracameral infusion of 0, 1, 3, 10, 30, 100 mM 3-ABA in 0.1 M PBS, pH 7.4 during ischemia. Morphologic and morphometric evaluation at 7 days after reperfusion showed that 3-ABA at 3 mM and above significantly ameliorated the ischemic/reperfusion damage to the retina. In addition, at 10 mM 3-ABA inhibited the characteristic ladder pattern in DNA gel analysis seen in apoptosis of retinal neurons after ischemia/reperfusion. Hence, PARP may be involved in retinal cell loss after ischemia/reperfusion insult probably through the apoptotic pathway.


Thorium and uranium contents in human urine: influence of age and residential area.
Inductively coupled plasma mass spectrometry (ICP-MS) has been used for the determination of (232)Th and (238)U in urine of unexposed Jordanian subjects living in six cities. The range of (232)Th excretion in all subjects was found to be 1.4-640 microBq d(-1) with an average of 34.8 microBq d(-1) (geometric mean 15.8 microBq d(-1)). Results showed no statistically significant correlation with age and residential area. The average value obtained is in agreement with levels considered normal in some recent publications. The average value of (238)U in all samples was found to be 3955 microBq d(-1) (geometric mean 1107 microBq d(-1)), which is higher than reported figures from Germany and India, but in agreement with those figures given in ICRP publication, number 23. The mean values of the different groups were found to be proportional to age up to 60 years. A noticeable drop is observed for subjects greater than 60 years old.


Rescue of an intracellular avirulent Rhodococcus equi replication defect by the extracellular addition of virulence-associated protein A.
Rhodococcus equi is a facultative intracellular bacterium that can escape from bactericidal mechanisms associated with phagocytosis. Virulence-associated protein A (VapA), encoded on a virulence-associated plasmid, is essential for intracellular survival in macrophages, but its function is not known. Here, we show that the extracellular addition of recombinant glutathione S-transferase (GST)-VapA fusion protein rescued the intracellular replication defect of a mutant lacking the vapA gene. Furthermore, the virulence-plasmid-cured strain could also multiply to nearly wild-type levels by the addition of GST-VapA. The present data suggest that VapA can alter the intraphagocytic environment, thereby affecting its suitability for the growth of R. equi.


Assessment of Pregabalin Use by Hair Testing.
The detection and analysis of drugs in hair has progressively emerged as a consequence of the enhanced sensitivity of analytical techniques used in forensic toxicology; a greater advantage in using this matrix respect to classical ones (i.e., urine and blood) is an easier and noninvasive sample collection, even when the careful supervision of law-enforcement officers is required to avoid the risk that the sample may be adulterated or replaced. Moreover, according to the length of the hair, the history of drug exposure can be retrospectively monitored from few weeks up to months or years since sample collection. Given the potential negative effects of pregabalin, an antiepileptic and analgesic drug with a high risk of misuse and abuse, the laboratory was asked to test for the drug in hair. A new ultrahigh-performance liquid chromatography coupled to tandem mass spectrometry was developed. The method involves incubation of 25 mg of cut hair in acetonitrile for 2 h in an ultrasonic bath and separation on an Acquity HSS C18 column (150 × 2.1 mm × 1.8 µm) maintained at 50°C in a thermostatically controlled oven. A gradient elution was performed. The method was fully validated according to international standards. The limit of quantitation of the test was 10 pg/mg. Five authentic cases of pregabalin in hair segments were tested using the method and the results were in the range 17-1487 pg/mg. This new method was found suitable to monitor both patients under pregabalin therapy and dependent subjects.


Generative naming in Parkinson disease patients.
The generative naming ability (verbal fluency) of 88 idiopathic Parkinson disease (PD) patients was evaluated and compared to that of 21 Alzheimer disease (AD) patients and 43 normal age- and education-matched normal control subjects. The PD patients were classified according to whether they scored within the normal range on the Mini-Mental State Examination (MMSE), a score of 27 or higher, or in the abnormal range, a score of 26 or lower. Semantic and letter generative naming tasks were administered to assess verbal fluency. Results of the study provide evidence that letter category naming is inherently more difficult than semantic category naming; that age significantly affects generative naming; that PD patients with normal MMSE scores were significantly inferior to normal control subjects in generative naming even after the effects of age and mental status are controlled; that PD patients with non-normal MMSE scores performed like AD patients after controlling for the effects of age and mental status; and, that ideational perseveration is the most common type of error response for all subject groups.


Using action learning in reflective practice.
Action learning encourages individuals to use reflective processes such as group support and self-directed learning. A staff development programme for nurses in a neurology unit adopted this approach. Action learning groups were used by staff nurses for six months and were evaluated through interviews and questionnaires. Nurses had positive experiences as they developed their practice through the support of others.


Changes in urinary pathogens and their antibiotic sensitivities, 1971-1992.
Unselected urinary pathogens from general practice and hospital have been tested for sensitivity to a range of antimicrobial agents for the last 22 years. There have been substantial changes. In general practice there has been a considerable increase in the proportion of staphylococcal infections from 5.1% to a peak of 14.8% in 1982 and a more recent decline to 4.0%. There has also been a decrease in the proportion caused by proteus mirabilis, from 9.2% to 4.3%. Similar, but smaller, changes have been observed in the proportions of hospital urinary tract infections caused by these organisms, while the proportion of hospital infections due to Klebsiella spp. and Enterobacter spp. has fallen from 16.8% to 7.3%. These and other changes have been reflected in the changing patterns of sensitivity to antibiotics. In particular, sensitivity of urinary pathogens to ampicillin/amoxycillin has continued to fall both in general practice and in hospital. Nalidixic acid resistance is becoming more important as the proportion of Gram-positive urinary pathogens (especially enterococci) increases. More organisms were sensitive to ciprofloxacin than the other drugs tested, with little evidence of increasing resistance.


"Single-Operator" Technique for Advancing the Orbital Atherectomy Device.
We assessed the feasibility and safety of the "single-operator" technique in which the operator autonomously advanced the orbital atherectomy (OA) device while maintaining wire position. Severe coronary artery calcification (CAC) increases the complexity of percutaneous coronary intervention (PCI), and is associated with lower procedural success rates and higher rates of adverse outcomes, including death, myocardial infarction, target-vessel revascularization, and stent thrombosis. OA is an effective treatment strategy to facilitate optimal stent expansion. Reluctance with the utilization of OA may stem from operator inexperience, unavailability of an experienced assistant, and the potential for proximal and distal wire migration during advancement of the device, leading to increased procedural and fluoroscopic time. Fifty consecutive patients who underwent OA from February 2014 to September 2016 were included in this prospective study. The primary endpoint was successful delivery of the OA device to the lesion while maintaining distal wire position and procedural success. The primary endpoint was achieved in all 50 patients (100%). The 30-day major adverse cardiac and cerebrovascular event rate was 6.0%, due to death (2%) and myocardial infarction (4%). Target-vessel revascularization, stroke, and stent thrombosis did not occur. Perforation occurred in 2%. Slow-flow occurred in 4%, but resolved with intracoronary vasodilator therapy and achieved Thombolysis in Myocardial Infarction grade 3 flow. Flow-limiting dissection did not occur. The single-operator technique is feasible, can be used to maintain wire position while the OA device is advanced, and obviates the need for a skilled assistant when advancing the OA device.


Male-female literacy differential in India--1981.
The author examines inequalities in the literacy rates between males and females in India. Regional variations in literacy are examined by district using maps. "The male-female literacy differential is low in coastal, peripheral and metropolitan areas and is high in inland and mountainous areas. These regional disparities are the product of differences in length of educational background, age at marriage, level of urbanisation, standard of living and proportion of socially conservative and backward sections of society.... The study in spatial dimension provides a strong base for the removal of sex biased discrimination in society."


Congenital primary upper eyelid entropion.
A case of primary congenital upper eyelid entropion ( PCUEE ) is reviewed. The author proposes a congenital shortness of the levator muscle with anomalous insertion onto the tarsal plate as the etiology, and a new simplified surgical correction is described. The classification of PCUEE as a syndrome with multiple congenital anomalies is supported, and the need for a complete systemic evaluation is stressed. Congenital primary upper eyelid entropion is an exceedingly rare condition. In 1969, Hiles and Wilder reviewed the 13 known cases in the ophthalmic literature, and presented a new case. They suggested the possibility that congenital upper eyelid entropion was part of a syndrome involving multiple systemic anomalies. Surgical correction of the ectropion is usually necessitated by corneal erosion secondary to trichiasis, and a multifarious assortment of surgical procedures has been described. The following is a case report of primary congenital upper eyelid entropion which corroborates the categorization as a syndrome, suggests a pathophysiologic abnormality of the eyelid as the etiology, and describes a new, simplified technique of surgical repair.


The effects of person-centered or other supportive interventions in older women with osteoporotic vertebral compression fractures-a systematic review of the literature.
Vertebral compression fracture (VCF) is a common fragility fracture and the starting point of a lasting, painful, disabling condition. The aim was to summarize evidence of person-centered/non-medical interventions supporting women with VCF. Results show small numbers of studies with only probable effect on function, pain, QoL, fear of falling, and psychological symptoms. The vertebral compression fracture (VCF) caused by osteoporosis is the third most common fragility fracture worldwide. Previously, it was believed that the pain caused by VCF was self-subsiding within weeks or a few months post-fracture. However, this positive prognosis has been refuted by studies showing that, for the great majority of patients, the VCF was the starting point of a long-lasting, severely painful, and disabling condition. The low number of studies focusing on the experience of the natural course of VCF, and what support is available and how it is perceived by those affected, calls for further investigation. Strengthening older patients' sense of security and increasing confidence in their own abilities are of great importance for successful rehabilitation following VCF. More research is needed to identify resources, possibilities, and strategies that can assist older patients to reach their goals to improve well-being. The purpose of this systematic review was to identify and summarize the current evidence of person-centered or other structured non-medical/non-surgical interventions supporting older women after experiencing an osteoporotic VCF. A systematic literature search was conducted on the MeSH terms encompassing osteoporosis and vertebral compression fractures in the PubMed-MEDLINE and Cumulative Index for Nursing and Allied Health Literature (CINAHL) databases during March through June 2015. The initial search identified 8789 articles, but only seven articles (six randomized controlled trials and one observational study with a control group) met the inclusion criteria. It became evident from the current study that the availability of evidence on the effects of non-medical interventions aiming to support older women with VCF is limited, to say the least. The trials included in this review have few limitations and were mainly considered to be of moderate quality. This systematic literature review suggests that non-medical interventions aiming to support older women with VCF might decrease levels of pain and use of analgesic as well as promote improved physical mobility and function. These interventions would probably result in an improved difference in experiences of fear of falling and perceived psychological symptoms, but would only slightly improve quality of life. However, given the nature of the seven studies, potential biases in patient selection, issues around precision with small cohorts, and failure to control for confounders, makes it difficult to draw a definitive conclusion about the significant effects of non-medical interventions. Incurring a VCF is a complex and diverse event, necessitating equally complex interventions to identify new ways forward. However, to date, interventions struggle with a risk of selection bias in that only the needs of the healthiest of the population are addressed and the voices of the remaining majority of the people affected by VCF are unheard.


Alternatively activated dendritic cells regulate CD4+ T-cell polarization in vitro and in vivo.
Interleukin-4 is a cytokine widely known for its role in CD4(+) T cell polarization and its ability to alternatively activate macrophage populations. In contrast, the impact of IL-4 on the activation and function of dendritic cells (DCs) is poorly understood. We report here that DCs respond to IL-4 both in vitro and in vivo by expression of multiple alternative activation markers with a different expression pattern to that of macrophages. We further demonstrate a central role for DC IL-4Rα expression in the optimal induction of IFNγ responses in vivo in both Th1 and Th2 settings, through a feedback loop in which IL-4 promotes DC secretion of IL-12. Finally, we reveal a central role for RELMα during T-cell priming, establishing that its expression by DCs is critical for optimal IL-10 and IL-13 promotion in vitro and in vivo. Together, these data highlight the significant impact that IL-4 and RELMα can have on DC activation and function in the context of either bacterial or helminth pathogens.


Estimating influenza and respiratory syncytial virus-associated mortality in Western Kenya using health and demographic surveillance system data, 2007-2013.
Influenza and respiratory syncytial virus (RSV) associated mortality has not been well-established in tropical Africa. We used the negative binomial regression method and the rate-difference method (i.e. deaths during low and high influenza/RSV activity months), to estimate excess mortality attributable to influenza and RSV using verbal autopsy data collected through a health and demographic surveillance system in Western Kenya, 2007-2013. Excess mortality rates were calculated for a) all-cause mortality, b) respiratory deaths (including pneumonia), c) HIV-related deaths, and d) pulmonary tuberculosis (TB) related deaths. Using the negative binomial regression method, the mean annual all-cause excess mortality rate associated with influenza and RSV was 14.1 (95% confidence interval [CI] 0.0-93.3) and 17.1 (95% CI 0.0-111.5) per 100,000 person-years (PY) respectively; and 10.5 (95% CI 0.0-28.5) and 7.3 (95% CI 0.0-27.3) per 100,000 PY for respiratory deaths, respectively. Highest mortality rates associated with influenza were among ≥50 years, particularly among persons with TB (41.6[95% CI 0.0-122.7]); and with RSV were among <5 years. Using the rate-difference method, the excess mortality rate for influenza and RSV was 44.8 (95% CI 36.8-54.4) and 19.7 (95% CI 14.7-26.5) per 100,000 PY, respectively, for all-cause deaths; and 9.6 (95% CI 6.3-14.7) and 6.6 (95% CI 3.9-11.0) per 100,000 PY, respectively, for respiratory deaths. Our study shows a substantial excess mortality associated with influenza and RSV in Western Kenya, especially among children <5 years and older persons with TB, supporting recommendations for influenza vaccination and efforts to develop RSV vaccines.


Compositional and Temporal Changes in the Gut Microbiome of Pediatric Ulcerative Colitis Patients Are Linked to Disease Course.
Evaluating progression risk and determining optimal therapy for ulcerative colitis (UC) is challenging as many patients exhibit incomplete responses to treatment. As part of the PROTECT (Predicting Response to Standardized Colitis Therapy) Study, we evaluated the role of the gut microbiome in disease course for 405 pediatric, new-onset, treatment-naive UC patients. Patients were monitored for 1 year upon treatment initiation, and microbial taxonomic composition was analyzed from fecal samples and rectal biopsies. Depletion of core gut microbes and expansion of bacteria typical of the oral cavity were associated with baseline disease severity. Remission and refractory disease were linked to species-specific temporal changes that may be implicative of therapy efficacy, and a pronounced increase in microbiome variability was observed prior to colectomy. Finally, microbial associations with disease-associated serological markers suggest host-microbial interactions in UC. These insights will help improve existing treatments and develop therapeutic approaches guiding optimal medical care.


Interaction between group IIb divalent transition-metal cations and 3-mercaptopropionic acid: a computational and topological perspective.
Density functional theory was applied to study the interaction of group IIb transition-metal cations (Zn(2+), Cd(2+), and Hg(2+)) with one and two fully or partially deprotonated 3-mercaptopropionic acid ligands. In this investigation, we determined the geometries of all possible complexes resulting from the coordination of the metal ions with the ligands at different binding sites selected on each ligand. The relative energies of the complexes, metal-ion affinities, free energies, and entropies were also determined. The natures of the bonds were critically analyzed by natural bond orbital (NBO) analysis and clarified further using the atoms-in-molecules (AIM) approach. The substantial influence of the solvent (water) polarization on the energetics, geometries, and bonding of the molecular complexes was also investigated by the conductor-like screening solvation model (COSMO). In an attempt to simulate the complexes in an aqueous environment, water molecules were added explicitly to complete the coordination sphere of the metal cations, and the corresponding metal-ion affinities were calculated to study the effect of microhydration.


Targeting the tumor proteasome as a mechanism to control the synthesis and bioactivity of matrix macromolecules.
Extracellular matrices (ECMs) are dynamic structures that provide cells not only with a structural support but, importantly, exhibit significant functional roles in the control of key cellular events such as adhesion, migration, proliferation, differentiation, and survival. In tumors, matrix effectors such as proteoglycans (PGs) and matrix metalloproteinases (MMPs) constitute major regulators of the interactions between tumor cells and their microenvironment and, therefore, they have been identified as potential molecular targets that are expected to advance the pharmacological treatment of cancer. ECMs composition is highly affected by cells through intrinsic regulatory mechanisms, such as the ubiquitin-proteasome system (UPS). Proteasome is a major cellular protease complex that controls the concentration and turnover of molecules in ECMs, including certain types of PGs, MMPs and collagens, and consequently, in the tumor microenvironment. Furthermore, proteasome activity is regulated by PG-derived intracellular glycosaminoglycan moieties revealing a critical inter-dependence of these compounds. Since ECMs renewal and degradation can be tightly regulated by proteasome activities, its modulation may be considered as a novel strategy to control the properties of tumor microenvironment. Currently, there are several proteasome inhibitors targeting distinct molecular pathways either approved or in clinical trials for the treatment of multiple cancers. In this review, the novel approach of targeting the proteasome to selectively regulate the synthesis and the bioactivity of certain matrix PGs and MMPs is presented and discussed.


[Paralytic hip dislocation in cerebral palsy--soft tissue surgical procedures].
Results of a combination of soft tissue procedures performed for the first time in treating paralytic dislocation of the hip in cerebral palsy are presented. All hip flexors and adductors release, along with possible transposition or elongation of knee flexors on the side of the dislocation (if knee contracture exceeded 20) were peformed. 75 hips in 57 patients were operated on. 54 patients were analyzed. The average age of the patients was 6.6 years, the average follow-up was 7 years. Excellent result was achieved in 33patients (61%), good in 10 (18,6%), fair in 4 (7,4%) poor in 7 patients (13%). Poor results were registered in patients over 10 years of age and in patients with athetosis. Results were assessed according to clinical finding, radiological finding (migrational percentage) and the ability of patients to walk. When based on radiological findings only, excellent results were achieved in 63 hips (84%). This combination of soft-tissue procedures which includes all muscles that take part in the dislocation proved to be very successful in achieving reposition. It can be recommended to patients suffering from the spastic form of cerebral palsy up to 10 years of age.


Should we supplement magnesium in critically ill patients?
Magnesium (Mg) deficiency is a common yet underdiagnosed problem in the ICU. Since only 1% of total body Mg is in the extracellular fluid, serum Mg concentrations may not adequately reflect Mg status. Utilizing techniques to measure intracellular Mg concentrations, Mg depletion has been shown to be present in about one half of all ICU patients. These patients have significantly higher morbidity and mortality rates than Mg-replete patients. Accurate identification of patients with Mg depletion requires a knowledge of the risk factors associated with Mg deficiency. These factors include poorly controlled diabetes mellitus, alcohol ingestion, severe diarrhea and steatorrhea, and the use of a number of pharmacologic agents that induce renal Mg wasting. Manifestations of Mg deficiency include hypokalemia, hypocalcemia, neuromuscular hyperexcitability, respiratory muscle weakness, and intractable arrhythmias. Mg deficiency may also play a role in the genesis of myocardial ischemia. In this article, we review the assessment, causes, and manifestations of Mg deficiency and suggest guidelines for adequate treatment.


Snai2 expression enhances ultraviolet radiation-induced skin carcinogenesis.
Snai2, encoded by the SNAI2 gene, has been shown to modulate epithelial-mesenchymal transformation (EMT), the conversion of sessile epithelial cells attached to adjacent cells and to the basement membrane into dissociated and motile fibroblastic cells. EMT occurs during development, wound healing, and carcinoma progression. Using Snai2-null mice (Snai2(lacZ)), we evaluated the role of Snai2 in UV radiation (UVR)-induced skin carcinogenesis. In chronically UVR-exposed nontumor-bearing skin from Snai2-null mice, inflammation and epidermal proliferation were decreased compared with wild-type (+/+) skin. Snai2-null mice had a consistently lower tumor burden than +/+ mice. In addition, null mice developed fewer aggressive spindle cell tumors, believed to arise from squamous cell carcinomas that have undergone EMT, than +/+ mice; however, the difference in tumor type distribution between the two genotypes was not statistically significant. No metastases were observed in either the +/+ or Snai2-null mice. Using quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry, we showed that the spindle cell tumors in the Snai2-null mice demonstrated impaired EMT, as shown by decreased vimentin and increased cadherin 1 expression. This study confirms a role for Snai2 in EMT, but demonstrates that Snai2 expression is not required for the development or progression of UVR-induced skin tumors.


Shiga toxin binding to globotriaosyl ceramide induces intracellular signals that mediate cytoskeleton remodeling in human renal carcinoma-derived cells.
Shiga toxin is a bacterial toxin consisting of A and B subunits. Generally, the essential cytotoxicity of the toxin is thought to be mediated by the A subunit, which possesses RNA cleavage activity and thus induces protein synthesis inhibition. We previously reported, however, that the binding of the Shiga toxin 1-B subunit to globotriaosyl ceramide, a functional receptor for Shiga toxin, induces intracellular signals in a manner that is dependent on glycolipid-enriched membrane domains, or lipid rafts. Although the precise role of this signaling mechanism is not known, here we report that Shiga-toxin-mediated intracellular signals induce cytoskeleton remodeling in ACHN cells derived from renal tubular epithelial carcinoma. Using confocal laser scanning microscopy, we observed that Shiga toxin 1-B treatment induces morphological changes in ACHN cells in a time-dependent manner. In addition, the morphological changes were accompanied by the redistribution of a number of proteins, including actin, ezrin, CD44, vimentin, cytokeratin, paxillin, FAK, and alpha- and gamma-tubulins, all of which are involved in cytoskeletal organization. The transient phosphorylation of ezrin and paxillin was also observed during the course of protein redistribution. Experiments using inhibitors for a variety of kinases suggested the involvement of lipid rafts, Src family protein kinase, PI 3-kinase, and RHO-associated kinase in Shiga toxin 1-B-induced ezrin phosphorylation. Shiga toxin 1-B-induced cytoskeletal remodeling should provide an in vitro model that can be used to increase our understanding of the pathogenesis of Shiga-toxin-mediated cell injury and the role of lipid-raft-mediated cell signaling in cytoskeletal remodeling.


What Brazil is doing to promote healthy diets and active lifestyles.
To present the way the Brazilian government is addressing the prevention of nutrition-related non-communicable diseases (NR-NCDs). Innovative legislative and regulatory actions, mass communications and capacity building have been combined to create a comprehensive approach for addressing poor dietary and activity patterns in Brazil that are leading to obesity and NR-NCDs. Included are new nutrition-related initiatives in the labelling area, shifts in the types of food purchased for the school food programme, use of mass media to communicate components of the food guidelines, establishment of a smart shopping initiative, and training of teachers and health workers. The entire effort has taken several years to get underway. This paper describes the process and some of the initial changes seen.


The Confluence of Perceiving and Thinking in Consciousness Phenomenology.
The processual relation of thinking and perceiving shall be examined from a historical perspective as well as on the basis of methodically conducted first-person observation. Historically, these two psychological aspects of human knowledge and corresponding philosophical positions have predominant alternating phases. At certain historical points, thinking and perceiving tend to converge, while in the interim phases they seem to diverge with an emphasis on one of them. While at the birth of modern science, for instance, these two forms of mental life were deeply interlinked, today they seem to be separated more than ever before - as a number of scientific crises have shown. Turning from the outer to the inner aspect of this issue, a phenomenological view becomes relevant. In terms of the consciousness phenomenology developed by Steiner (1861-1925) and Witzenmann's (1905-1988) Structure Phenomenology, this article will show how a methodical integration of thinking and perceiving can be carried out on the basis of first-person observation. In the course of a skilled introspective or meditative self-observation the individual's own mental micro-actions of separating and integrating come into view, jointly constituting what we usually call thinking and perceiving. Consequently, this approach includes a conceptual as well as a perceptual dimension the experimental confluence of which ties in with the methodological core principle of modern natural science. At the same time, making this principle explicit may open the way to a further development of human consciousness and its scientific delineation.


Myeloid neoplasms with germ line RUNX1 mutation.
Familial platelet disorder with propensity to myeloid malignancies (FPD/AML) is an autosomal dominant disorder characterized by quantitative and/or qualitative platelet defects with a tendency to develop a variety of hematological malignancies. Heterozygous germ line mutations in the RUNX1 gene are responsible genetic events for FPD/AML. Notably, about half of individuals in the family with germ line mutations in RUNX1 develop overt hematological malignancies. The latency is also relatively long as an average age at diagnosis is more than 30 years. Similar to what is observed in sporadic hematological malignancies, acquired additional genetic events cooperate with inherited RUNX1 mutations to progress the overt malignant phase. Reflecting recent increased awareness of hematological malignancies with germ line mutations, FPD/AML was added in the revised WHO 2016 classification. In this review, we provide an update on FPD/AML with recent clinical and experimental findings.


Age-related changes in vitamin D metabolites, osteocalcin, alkaline phosphatase and parathyrin in normal Chinese women in Taipei.
To evaluate the age-related changes in the bone remodeling rate, the vitamin D status, and parathyroid function of healthy Chinese women, we selected two serum markers of bone turnover, osteocalcin and alkaline phosphatase (ALP). These markers as well as vitamin D metabolites and parathyrin (parathyroid hormone, PTH) were tested in healthy Chinese female volunteers aged 18 to 80 years residing in the Taipei urban area. The results showed no significant change with aging in the 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D) and immunoreactive c-terminal PTH (i-cPTH) serum levels. However, there was a trend towards lower 25(OH)D levels at the two extremes of age. The serum levels of 1,25(OH)2D and i-cPTH were comparable with reports of other countries. The serum 25(OH)D levels of our subjects were in general lower than those reported in U.S. white women, but similar to those of European women. The serum osteocalcin levels showed a triphasic change: high in early adulthood, decreasing during the 4th decade of life and then increasing continuously until age 70. After age 70, a decreasing trend was again seen. The serum ALP levels showed a continuous increase from the 3rd to the 8th decade of life. All of the subjects had their bone mineral density (BMD) measured. Linear or polynominal regression analysis as well as multiple regression analysis failed to show a significant correlation between the serum parameters and the BMD measurements at various sites.(ABSTRACT TRUNCATED AT 250 WORDS)


In Vitro Bioaccessibility and Antioxidant Activity of Coffee Silverskin Polyphenolic Extract and Characterization of Bioactive Compounds Using UHPLC-Q-Orbitrap HRMS.
Coffee silverskin (CS), the main by-product in the coffee industry, contains a vast number of human health-related compounds, which may justify its exploitation as a functional food ingredient. This study aimed to provide a comprehensive analysis of the polyphenolic and alkaloid profile through UHPLC-Q-Orbitrap HRMS analysis. The bioaccessibility of total phenolic compounds and changes in the antioxidant activity during an in vitro gastrointestinal digestion were also evaluated through spectrophotometric tests (TPC by Folin-Ciocalteu, ABTS, DPPH, and FRAP), to elucidate their efficacy for future applications in the nutraceutical industry. Caffeoylquinic and feruloylquinic acids were the most representative polyphenols, with a mean concentration of 5.93 and 4.25 mg/g, respectively. Results showed a high content of caffeine in the analyzed CS extracts, with a mean value of 31.2 mg/g, meaning a two-fold increase when compared to coffee brews. Our findings highlighted that both the bioaccessibility and antioxidant activity of CS polyphenols significantly increased in each in vitro gastrointestinal digestion stage. In addition, the colon stage might constitute the main biological site of action of these antioxidant compounds. These results suggest that in vivo, the dietary polyphenols from CS might be metabolized by human colonic microflora, generating metabolites with a greater antioxidant activity, increasing their well-known beneficial effects.


Cleft lip - a comprehensive review.
Orofacial clefts comprise a range of congenital deformities and are the most common head and neck congenital malformation. Clefting has significant psychological and socio- economic effects on patient quality of life and require a multidisciplinary team approach for management. The complex interplay between genetic and environmental factors play a significant role in the incidence and cause of clefting. In this review, the embryology, classification, epidemiology, and etiology of cleft lip are discussed. The primary goals of surgical repair are to restore normal function, speech development, and facial esthetics. Different techniques are employed based on surgeon expertise and the unique patient presentations. Pre-surgical orthopedics are frequently employed prior to definitive repair to improve outcomes. Long term follow up and quality of life studies are discussed.


Psychological values as protective factors against sexist attitudes in preadolescents.
Sexist attitudes are one of the factors that justify domestic violence. Positive psychology can provide keys to prevent sexist violence at an early age. Psychological values are a group of psychological strengths in a person's development. They provide important clues for the prevention of gender-based violence. This study presents an assessment of two groups of variables, sexist attitudes and beliefs and psychological values, in a sample of 449 (213 boys and 236 girls) preadolescents from various schools (mean age: 12). We analyze the relationship between these variables. We used the Values in Action Inventory (VIA-Y), the Questionnaire of Attitudes towards Diversity and Violence (CADV) and the Ambivalent Sexism Inventory (ASI). The results show that sexism variables are related to each other and negatively to the psychological values in boys and girls. We discuss the importance of prevention programs being appropriately developed and, probably, different programs for each sex.


Ionizing radiation activates late herpes simplex virus 1 promoters via the p38 pathway in tumors treated with oncolytic viruses.
Ionizing radiation potentiates the oncolytic activity of attenuated herpes simplex viruses in tumors exposed to irradiation at specific time intervals by inducing higher virus yields. Cell culture studies have shown that an attenuated virus lacking the viral gamma(1)34.5 genes underproduces late proteins whose synthesis depends on sustained synthesis of viral DNA. Here we report that ionizing radiation enhances gene expression from late viral promoters in transduced cells in the absence of other viral gene products. Consistent with this result, we show that in tumors infected with the attenuated virus, ionizing radiation increases 13.6-fold above baseline the gene expression from a late viral promoter as early as 2 hours after virus infection, an interval too short to account for viral DNA synthesis. The radiation-dependent up-regulation of late viral genes is mediated by the p38 pathway, inasmuch as the enhancement is abolished by p38 inhibitors or a p38 dominant-negative construct. The p38 pathway is not essential for wild-type virus gene expression. The results suggest that ionizing radiation up-regulates late promoters active in the course of viral DNA synthesis and provide a rationale for use of radiation to up-regulate cytotoxic genes introduced into tumor cells by viral vectors for cytoreductive therapy.


Viruslike particles in muscle from a patient with amyotrophic lateral sclerosis.
An electron microscopic study of muscle and central nervous tissue from a case of amyotrophic lateral sclerosis showed crystalline arrays of 20 to 24 nm viruslike particles in muscle. The particles were located between the myofibrils, adjacent to the Z bands, and near the perinuclear region, but were never seen within the nucleus. Cell cultures from the same muscle specimens showed no such particles. Central nervous system tissues and cultures also failed to show viruslike particles. The cultures were negative by the indirect fluorescent antibody technique with serums from patients with amyotrophic lateral sclerosis. The nature of these particles or their relationship to amyotrophic lateral sclerosis is unknown.


Isoenzymes of two aminotransferases among Trypanosoma vivax in Nigerian cattle.
During a period of three months, thin-layer starch-gel electrophoresis was used to examine the isoenzymes of alanine and asparate aminotransferases from samples of T. vivax collected from naturally infected Nigerian cattle. Experimentally infected cattle sheep and goats were also studied. Three patterns, termed Sets 1,2 and 3, differed in both enzymes. The stability of the enzyme patterns was generally confirmed in experimental animals. The results are discussed in relation to subspeciation in T. vivax.


Serum CD26 levels in patients with gastric cancer: a novel potential diagnostic marker.
CD26 is an ectoenzyme with dipeptidyl peptidase 4 (DPP4) activity expressed on a variety of cell types. Considering that serum CD26 levels have been previously associated with different cancers, we examined the potential diagnostic value of serum CD26 levels in gastric cancer. Soluble serum CD26 levels were measured in pre and postoperative serum samples of 30 patients with gastric cancer and in 24 healthy donors by a specific ELISA kit. We found significantly lower serum CD26 levels in patients with gastric cancer (557.7 ± 118.3 pg/mL) compared with healthy donors (703.4 ± 170.3 pg/mL). Moreover patients with HER2 positive tumors had significantly lower CD26 serum levels (511.8 ± 84.8 pg/mL) compared with HER2 negative tumors (619.1 ± 109.9 pg/mL, p = 0.006). A binary logistic model having gastric cancer as the dependent variable while age, gender, CEA, CA19.9 and CD26 levels as covariates, showed that CD26 serum levels were independently associated with gastric cancer presence. Indeed after 3 months from surgery serum CD26 levels significantly increased (700.1 ± 119.9 pg/mL vs 557.7 ± 118.3 pg/ml) in all patients (t = -4.454, p < 0.0001). This is a preliminary study showing that the measurement of serum CD26 levels could represent an early detection marker for gastric cancer.


[Sexual abuse at schools in Cameroon: results of a survey-action program in Yaounde].
The purpose of this questionnaire-based study was to determine the incidence of sexual abuse in schools in Yaoundé, Cameroon, to assess the extent of teacher involvement in such acts and to provide children an opportunity to come forward with their experiences. The author hypothesized that the number of sexual abuse victims was increasing and that the most frequent abusers were teachers, school staff, and classmates. To check this hypothesis, a total of 1710 questionnaires were sent to 10 public and private secondary schools between January 4 and April 30, 1999. The response rate was 98.7%. A total of 269 students reported being sexual abused before the age of 16 for an overall incidence of 15.9%. There were 74 boys (27.5%) and 195 girls (72.5%) with a mean age 11.6 years (range 4 to 15 years) at the time of abuse. Sexual abuse involved rape in 38.7% of cases, fondling in 54.6% and pornographic scenes in 6.7%. Of the 274 sexual abusers identified, 86.5% were men and 13.5% were women. Sexual abuse took place within the family in 31.4% of cases and outside the family setting 68.6%. Sexual abuse occurred in a school setting in approximately 15% of cases and involved classmates in approximately 30%. The alleged extrafamilial abusers were teachers in 7.9% of cases and tutors in 7.6%. Survey data supports the working hypothesis of this study and warrants implementation of a program to prevent sexual abuse in schools.


Corrosion Failure Mechanism of Associated Gas Transmission Pipeline.
Corrosion has been responsible for several gas pipeline leakage accidents; thus, clarifying its failure mechanisms is a precondition to prevent such accidents. On the basis of failure analysis of corroded pipe sections, laboratory exposure tests were conducted by simulating three possible corrosion environments inside a gas pipeline. The corrosion rate indicated by depth change was adopted in this study. Scanning electron microscopy and X-ray diffraction were used to analyze corrosion products. Results showed that the specimens completely immersed in condensate water were generally corroded and that the specimens exposed to gas were locally corroded. However, the corrosion rate of the latter was slightly lower; hence, no autocatalysis of occluded corrosion cell occurred in the formation of corrosion pit, and uniform corrosion occurred in the precipitation location of condensate water. The areas in the range of 5 mm below the waterline indicated severe corrosion, and the rate could reach twice that of other areas. The corrosion products were mainly FeO(OH) and FeCO₃, thereby proving that the corrosion failure of pipelines was caused by oxygen absorption corrosion and CO₂ corrosion. Suggestions were presented to control corrosion failure of associated gas pipelines.


Economical and Easily Obtainable Tools to Manually Develop Lateral Flow Immunoassay Strips.
The development of inexpensive and highly functional lateral flow devices, which utilize simple and affordable tools, can make them accessible to many populations with insufficient resources. Therefore, this study aims to provide a method to overcome the cost challenges associated with using expensive manufacturing technologies and machinery, particularly during pandemics and upon urgent need. Here, in-house lateral flow strips to detect serum antibodies were developed using low-priced and easily available tools such as adhesive tape and CytoSep layers. The developed lateral flow immunoassay strips presented here produced signals with 93.3 and 96.6% sensitivity for SARS-CoV-2 nucleocapsid protein-specific IgM and IgG antibodies, respectively. The specificity obtained from the developed strips was 96.6% for SARS-CoV-2 nucleocapsid protein-specific IgM and 100% for the IgG antibodies by applying only 5 μL from the serum samples. The proposed design was entirely made manually to ensure a method that would make lateral flow devices available to many populations in need around the globe.


Fractionation and solvent-free MALDI-MS analysis of polymers using liquid adsorption chromatography at critical conditions in combination with a multisample on-target homogenization/transfer sample preparation method.
A solvent-free homogenization/transfer matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) method is described for the preparation and precise transfer of up to 100 samples simultaneously on a single MALDI plate. This method is demonstrated using a poly(ethylene oxide) (PEO) mixture consisting of different molecular weights (500-6000) and end groups (PEO, dimethoxy-PEO, monomethoxy monomethacrylate-PEO, and dimethacrylate-PEO) that was fractionated using liquid adsorption chromatography at critical conditions. Off-line fractionation is performed prior to the on-target homogenization/transfer solvent-free sample preparation and MALDI mass analysis. The miniaturization of the solvent-free MALDI approach allowed analysis of less than 2 microg per PEO component per fraction corresponding to approximately 200 pmol for PEO 6000. The amounts of polymer sample used for LC separation and the quality of the MS results are equivalent to the "dry spray" method; however, three times more fractions were collected and analyzed with the newly developed hyphenated approach. The off-line method eliminates optimization of, for example, spray conditions or spreading of organic solvents on the MALDI plate that occurs with droplet deposition methods. The widespread applications of MALDI make this solvent-free, multisample method particularly important as it expands the capabilities for obtaining mass measurements with great efficiencies in areas with increased sample numbers. In addition, the solvent-free method is well suited for automated MALDI analysis as it virtually eliminates the "dead-spot" phenomenon.


[Qingli shengjing pills decrease apoptosis of germ cells and expressions of fas and fasL in male mice infected with Escherichia coli].
To study the effects of Qingli Shengjing Pills (QSP) on the apoptosis of germ cells and expressions of Fas and FasL in male mice infected with Escherichia coli (E. coli), and to clarify the molecular mechanism of QSP in the treatment of male infertility induced by E. coli infection. Fifty male mice were injected with E. coli via the bladder to make infection models, and at 15 dpi equally randomized into five groups: an untreated, a high-dose QSP (22.5 g/ml), a medium-dose QSP (13.5 g/ml), a low-dose QSP (4.50 g/ml) and a Furadantin treatment group, which were coded as MN, MTa, MTb, MTc and MTd, respectively. Another 10 mice were injected with saline and included in the control group coded as CT. After 10 days of oral medication, the apoptosis of germ cells in the testis of the mice was detected by flow cytometry, the expressions of Fas and FasL determined by immunohistochemistry and the histopathological changes observed simultaneously. After the treatment, the apoptosis of germ cells was observed in all the infected groups, and the apoptosis level in MN (57.44%) was significantly higher than that in CT (28.54%), MTb (28.59%) or MTa (30.11%) (P < 0.01) but had no significant difference from that in MTc (46.54%) or MTd (43.41%) (P > 0.05). The expressions of Fas and FasL proteins were significantly higher in MN than in CT, MTa, MTb, MTc and MTd (P < 0.01). Histopathological changes of the testis tissue were observed in MN, but not in other groups. E. coli infection could increase the apoptosis rate of germ cells and the expressions of Fas and FasL proteins. Qingli Shengjing Pills, capable of enhancing reproductivity by reducing the expressions of Fas and FasL and apoptosis of germ cells, can be used as one of the effective drugs for infertility induced by E. coli infection.


Reliability of physical functioning measures in ambulatory subjects with MS.
One of the primary reasons for measuring outcomes during rehabilitation is to determine the effect of physiotherapy. Repeated measurement situations are susceptible to several sources of error, including inconsistencies caused by the subject, the procedure, the instrument and the examiner. Therefore, the reliability of the measures needs to be examined. The present study used a repeated-measures design. Two studies were undertaken to examine the test-retest and inter-rater reliability for physical functioning measures. The interval between the measurements was one week. The sample consisted of 19 ambulatory subjects with multiple sclerosis (MS) in the test-retest and nine subjects in the inter-rater reliability study. The measures were selected to assess different domains of the World Health Organization International Classification of Functioning, Disability and Health (WHO, 2001). Several parameters of the Box and Block Test (BBT), the Berg Balance Scale (BBS), the Kela Coordination test, the postural stability test, the timed 10-metre gait test, the six-minute walk test, the shoulder tug test, grip strength, maximal isometric force of the knee extensors, muscle endurance tests, the modified Ashworth Scale and passive straight leg raise test were examined in terms of reliability. The intra-class coefficient (ICC) values for test-retest reliability were >0.80 in 17 of 23 parameters, and correspondingly so in 20 out of 26 parameters for inter-rater reliability. Poor reliability (defined as ICC < or = 0. 60) was obtained only for the patient classification index (PCI) of the six-minute walk test in the test-retest reliability study. In general, the coefficient of variation was good. A moderate amount of variability was discovered for the Kela Coordination test, and for postural stability and muscle endurance tests. The data obtained from the modified Ashworth Scale and the shoulder tug test were highly skewed and the percentage of agreement ranged between 63.9% and 93.4%. The study revealed acceptable test-retest and inter-rater reliability of these measures in ambulatory subjects with MS, with the exception of the Modified Ashworth Scale and the shoulder tug test.


Breast Carcinoma Shown on 99mTc-HYNIC-TOC Study Performed to Evaluate Tumor-Induced Osteomalacia.
A 74-year-old woman with a history of suspected tumor-induced osteomalacia underwent 99mTc-HYNIC-TOC scintigraphy to search potential culprit tumor. The images showed one in the middle shaft of left femur without corresponding morphology change on the CT portion of the subsequent SPECT/CT images. The patient declined surgical exploration of the left femur. Another activity was in the right breast, which was resected and pathologically confirmed as breast carcinoma. Postsurgically, the patient's symptoms were not improved. Four years later, a repeat 99mTc-HYNIC-TOC scintigraphy showed more prominent activity in the left femur with gross abnormality on the corresponding CT images.


Evolutionary aspects of accuracy of phenylalanyl-tRNA synthetase. Accuracy of fungal and animal mitochondrial enzymes and their relationship to their cytoplasmic counterparts and a prokaryotic enzyme.
Phenylalanyl-tRNA synthetases from mitochondria of yeast and hen liver resemble their corresponding cytoplasmic counterparts. Whereas slight intraspecies differences at the amino acid binding site, reflecting variations in the structures of these distinct enzymes, are exploitable by phenylalanine analogues, no intraspecies difference can be noted for the strategies to achieve the high fidelity of protein synthesis. While the yeast mitochondrial enzyme follows the pathway of posttransfer proofreading, the hen liver mitochondrial enzyme uses a tRNA-dependent pretransfer proofreading in the case of the natural amino acids. The accuracy of mitochondrial phenylalanyl-tRNA synthetases appears to be even better than the accuracy of the corresponding cytoplasmic enzymes. Interspecies rather than intraspecies differences for the functional role of certain amino acid residues of the enzymes further indicate the close relationship of the intracellular heterotopic isoenzymes. By use of a highly sensitive immunospotting procedure, common antigenic determinants are detected only within the enzymes from the two intracellular compartments of the same organism. The results suggest the origin of the cytoplasm-mitochondrion isoenzyme pair by independent gene duplication of the ancestral nuclear gene. A similarity of mitochondrial enzymes to the phenylalanyl-tRNA synthetase from Escherichia coli is not observed.


Frequencies of alleles and genotypes of the PRNP gene in Polish Red, Czech Pied and Czech Black-and-White cattle.
Frequencies of alleles and genotypes of the PRNP gene in 65 Polish Red cows kept under a conservation programme and 52 randomly chosen cows of two Czech breeds: Czech Pied (42) and Black-and-White (10) were studied. All cows were at the age of 4 years or older. It was found that the frequency of allele 5 (5 copies of the octapeptide repeat) ranged from 0.11 (Polish Red) to 0.00 (Czech Black-and-White) whereas the frequency of allele 6 (6 copies of the octapeptide repeat) ranged from 1.00 (Czech Black and White) to 0.89 (Polish Red). The highest frequency was found for the homozygous genotype 6/6 (1.00 in Czech Black-and-White) and the lowest frequency was detected for the heterozygous genotype 6/5 (0.143). In the studied cows the genotype 5/5 was not found. The higher frequency of allele 5 in the native breeds and its lower frequency or lack of this allele in the populations intensively selected for high milk production may suggest that alleles of the PRNP gene may be associated with milk production.


Myoelectric activity of the small bowel in mechanical obstruction and intra-abdominal bacterial contamination.
The myoelectric activity of the small bowel was evaluated in 6 rabbits following 24 h of complete small-bowel obstruction and in 6 rabbits during an intra-abdominal perfusion with a bacterial suspension containing Bacteroides fragilis and Escherichia coli. Myoelectric recordings were performed before and during pharmacological small-bowel stimulation with ceruletide. Following small-bowel obstruction both slow-wave frequency and spike activity were reduced. Ceruletide stimulation demonstrated a significantly decreased spike activity after 24 h of obstruction. Intra-abdominal bacterial contamination did not affect spontaneous slow-wave frequency and spike activity but induced complete resistance to ceruletide stimulation. Pharmacological stimulation is recommended as an additional method to evaluate the impairment of myoelectric activity in motility disorders.


The Welfare Cost of Perceived Policy Uncertainty: Evidence from Social Security.
Policy uncertainty reduces individual welfare when individuals have limited opportunities to mitigate or insure against the resulting consumption fluctuations. We field an original survey to measure the degree of perceived policy uncertainty in Social Security benefits and to estimate the impact of this uncertainty on individual welfare. Our central estimates show that on average individuals are willing to forgo 6 percent of the benefits they are supposed to get under current law to remove the policy uncertainty associated with their future Social Security benefits. This translates to a risk premium from policy uncertainty equal to 10 percent of expected benefits.


A centrifugation-based method for extraction of norovirus from raspberries.
A method was developed for extraction of noroviruses from raspberries. The method consists of removal of virus from fruit surfaces by alkaline extraction, then removal of residual food debris by centrifugation, followed by concentration of virus particles by ultracentrifugation. The efficiency of the extraction was estimated by comparison of reverse transcription PCR signals obtained from fruit extracts and the norovirus suspension that was used to contaminate the fruit. Noroviruses were recovered with at least 10% efficiency from 60-g raspberry samples (n = 10). The sample treatment reported here should be applicable for harnessing to any norovirus reverse transcription PCR and form the basis of a dependable method to detect noroviruses in raspberries.