Incidence of chromosomal anomalies in fetuses with isolated right aortic arch: A meta-analysis.
Right aortic arch (RAA) can be associated with chromosomal anomalies. However, the incidence of chromosomal anomalies when RAA is isolated (iRAA), ie, not associated with intracardiac anomalies, varies between different studies (0%-28.5%). We have performed a meta-analysis to allow a more accurate prenatal counselling. We searched PubMed, Embase, and Web of Science for articles related to chromosomal anomalies among iRAA fetuses until April 2019. A total of 22 relevant studies, including 670 fetuses, were selected in the final meta-analysis. The results revealed that the overall rates of chromosomal anomalies and 22q11.2 deletion in iRAA fetuses were 7.5% (95% confidence interval [CI], 4.7%-10.8%) and 4.3% (95% CI, 2.6%-6.4%), respectively, while the rates were lower in iRAA without extracardiac anomalies, 4.7% (95% CI, 1.1%-10.8%) and 2.4% (95% CI, 0.5%-5.7%). The rate of chromosomal or copy number variants including 22q11.2 deletion identified by chromosomal microarray analysis (CMA) in iRAA fetuses was 8.2% (95% CI, 5.0%-12.1%) and 3.7% (95% CI, 1.7%-6.6%), respectively, compared with 5.1% (95% CI, 2.5%-8.4%) and 2.4% (95% CI, 0.7%-5.1%) identified by traditional karyotyping. A considerable proportion of iRAA cases have associated chromosomal anomalies and prevalence of associated 22q11.2 deletion, and CMA is recommended if invasive prenatal testing is performed.


High-efficiency generation of plasmid cDNA libraries using electro-transformation.
A simple and efficient method for the construction of large cDNA libraries in plasmid vectors is described. Cloning efficiencies of greater than 1 x 10(6) recombinants per microgram starting RNA are easily obtained using electroporation. A detailed protocol for determining the optimal conditions using this novel approach is presented.


Chemical Diversity and Potential Target Network of Woody Peony Flower Essential Oil from Eleven Representative Cultivars (Paeonia × suffruticosa Andr.).
Woody peony (Paeonia × suffruticosa Andr.) has many cultivars with genetic variances. The flower essential oil is valued in cosmetics and fragrances. This study was to investigate the chemical diversity of essential oils of eleven representative cultivars and their potential target network. Hydro-distillation afforded yields of 0.11-0.25%. Essential oils were analyzed by GC-MS and GC-FID which identified 105 compounds. Three clusters emerged from multivariate analysis, representative of phloroglucinol trimethyl ether ('Caihui'), citronellol ('Jingyu', 'Zhaofen' and 'Baiyuan Zhenghui') and mixed (the rest of the cultivars) chemotypes. 'Zhaofen' and 'Jingyu' also exhibited low levels of other rose-related compounds. The main components were subjected to a target network approach. Drug-likeness screening gave 20 compounds with predictive blood-brain barrier permeation. Compound target network identified six key compounds, namely nerol, citronellol, geraniol, geranic acid, cis-3-hexen-1-ol and 1-hexanol. Top enriched terms in GO, KEGG and DisGeNET were mostly related to the central nervous system (CNS). Protein-protein interactions revealed a core network of 14 targets, 11 of which were CNS-related (targets for antidepressants, analgesics, antipsychotics, anti-Alzheimer's and anti-Parkinson's agents). This work provides useful information on the production of woody peony essential oils with specific chemotypes and reveals their potential importance in aromatherapy for alternative treatment of CNS disorders.


The application of Uniform Manifold Approximation and Projection (UMAP) for unconstrained ordination and classification of biological indicators in aquatic ecology.
The analysis of community structure in studies of freshwater ecology often requires the application of dimensionality reduction to process multivariate data. A high number of dimensions (number of taxa/environmental parameters × number of samples), nonlinear relationships, outliers, and high variability usually hinder the visualization and interpretation of multivariate datasets. Here, we proposed a new statistical design using Uniform Manifold Approximation and Projection (UMAP), and community partitioning using Louvain algorithms, to ordinate and classify the structure of aquatic biota in two-dimensional space. We present this approach with a demonstration of five previously published datasets for diatoms, macrophytes, chironomids (larval and subfossil), and fish. Principal Component Analysis (PCA) and Ward's clustering were also used to assess the comparability of the UMAP approach compared to traditional approaches for ordination and classification. The ordination of sampling sites in 2-dimensional space showed a much denser, and easier to interpret, grouping using the UMAP approach in comparison to PCA. The classification of community structure using the Louvain algorithm in UMAP ordinal space showed a high classification strength for data with a high number of dimensions than the cluster patterns obtained with the use of a Ward's algorithm in PCA. Environmental gradients, presented via heat maps, were overlayed with the ordination patterns of aquatic communities, confirming that the ordinations obtained by UMAP were ecologically meaningful. This is the first study that has applied a UMAP approach with classification using Louvain algorithms on ecological datasets. We show that the performance of local and global structures, as well as the number of clusters determined by the algorithm, make this approach more powerful than traditional approaches.


Epstein-Barr virus infection in allogeneic marrow grafting: lessons for transplant physicians and virologists.
The relationship between Epstein-Barr virus (EBV) and the host is profoundly disturbed by allogeneic bone marrow transplantation (BMT) because EBV resides in the recipient's hematopoietic system, which has to be destroyed in the majority of cases, and in the donor's hematopoietic system, i.e., the marrow graft. We have shown that EBV may be eradicated from some BMT recipients and that the virus may be transferred with the marrow graft. During the immediate post-transplant period oropharyngeal EBV excretion may occur which, by infecting passing B lymphocytes, may act as co-factor for acute graft-versus-host disease and help the virus to survive, despite the temporary depletion of its reservoir. The coexistence of totally different EBV strains in BMT recipients but not in healthy, untransfused controls, suggests that superinfection may by possible in case of immunodeficiency; alternatively, transfer of the virus by the reservoir itself (the B lymphocytes) might be the only effective route for superinfection. The generation of 'variant' strains during viral replication may form the basis of the vast polymorphism between wild-type EBV isolates in the population.


Spinal GABA receptors mediate brain delta opioid analgesia in Swiss Webster mice.
Morphine and heroin act on supraspinal mu-opioid receptors in ICR mice to activate descending noradrenergic and serotonergic systems to inhibit the tail flick response. Antinociception induced by supraspinal [D-Pen2,5]-enkephalin (DPDPE, delta agonist) involves a descending system mediated by spinal gamma-aminobutyric acid, GABAA and GABAB, receptors. Because in Swiss Webster mice the receptor selectivity of heroin changes to delta whereas morphine remains mu, the purpose of the present study was to determine whether this delta action of heroin was mediated spinally by GABAA and GABAB receptors. Bicuculline (GABAA receptor antagonist) and picrotoxin (chloride ion channel blocker) given intrathecally produced rightward shifts in the dose-response curves of DPDPE and heroin given intracerebroventricularly. Thus, spinal GABAA receptors were involved. Intrathecal administration of 2-hydroxysaclofen (GABAB receptor antagonist) also shifted the dose-response curves to the right. Thus, the antinociception produced by heroin, like DPDPE, by activation of delta receptors in the brain of Swiss Webster mice involved both GABAA and the GABAB receptors in the spinal cord.


Evaluation of cell-surface displayed synthetic consensus dengue EDIII cells as a potent oral vaccine candidate.
Dengue is a rapidly spreading mosquito borne tropical viral disease affecting hundreds of millions of people across the globe annually. The dengue virus (DENV) includes four genetically distinct serotypes that cause serious life-threatening infections, including dengue hemorrhagic fever/dengue shock syndrome. Dengue vaccine development is complicated by the possibility of vaccine-enhanced severe dengue disease due to antibody-dependent enhancement by pre-existing cross-reactivity, as well as homotypic antibodies. Thus, the development of an efficacious dengue vaccine conferring simultaneous and durable immunity to each of the four DENV serotypes has not yet been developed despite years of research. For mass immunization in deeply affected resource-limited countries, oral vaccination is considered more beneficial than conventional approaches. Therefore, in a continuing effort towards designing economical and potent vaccine candidates, the current study applied yeast surface display technology to develop an oral dengue vaccine candidate using whole recombinant yeast cells displaying the recombinant fusion protein of M cell targeting ligand Co1 fused to the synthetic consensus dengue envelope domain III (scEDIII). Female Balb/c mice were orally fed with recombinant yeast cells and immunogenicity in terms of systemic and mucosal immune responses was monitored. Immunofluorescence microscopy with dengue specific antibody and fluorescein isothiocyanate-conjugated anti-mouse IgG antibody clearly showed that recombinant protein Co1-scEDIII-AGA was localized on the cell surface of the respective clones in comparison with scEDIII-Co1 and Mock cells with no fluorescence. Oral dosage applications of surface displayed Co1-scEDIII-AGA stimulated a systemic humoral immune response in the form of dengue-specific serum IgG, as well as a mucosal immune response in the form of secretory immunoglobulin A (sIgA). Antigen-specific B cell responses in isolated lymphoid cells from the spleen and Peyer's patches further supported an elevated mucosal immune response. In addition, surface displayed Co1-scEDIII-AGA feeding elicited strong immune responses in comparison with scEDIII-Co1 and Mock following intraperitoneal booster with purified scEDIII antigen. Surface displayed preparations of Co1-scEDIII-AGA induced strong immunogenicity compared with non-displayed scEDIII-Co1. Prior studies have supported the neutralization potential of scEDIII constructs against all four serotypes. Thus, the oral administration of genetically engineered yeast whole cells displaying biologically active Co1-scEDIII fusion protein without any further processing shows prospective as a potent oral vaccine candidate against dengue viral infection.


Childhood obesity prevention from cell to society.
Nearly 40% of US children are overweight or obese. We propose that a cell-to-society integrative approach is needed that takes into account biology, early child development, home and childcare environments, and public policy. This approach requires researchers, families, and policy makers to work together to develop preventative strategies and interventions that benefit the nutrition and wellbeing of young children and their families, and ultimately the health of the nation.


Calicheamicins, a novel family of antitumor antibiotics: taxonomy, fermentation and biological properties.
A novel family of antitumor antibiotics, the calicheamicins, were isolated from the fermentation broth of Micromonospora echinospora subsp. calichensis. These antibiotics exhibited significant activity against Gram-positive and Gram-negative bacteria in vitro. Calicheamicin gamma 1I demonstrated antitumor activity against P388 leukemia and B16 melanoma in vivo.


Role of ribose deficit in rat testicular metabolism under conditions of overtraining.
Acute disorders of purine metabolism develop in rat testes under conditions of overtraining. These disorders are characterized by enhanced catabolism and reduced reutilization of purine mononucleotides and activation of lipid peroxidation of membrane structures against the background of reduced activities of the pentose cycle and antioxidant system. Administration of D-ribose to rats subjected to overtraining improves purine reutilization, stimulates the pentose cycle work, inhibits lipid peroxidation in membrane structures of the testes, and saves the testicular incretory function.


Increased EEG coherence in long-distance and short-distance connectivity in children with autism spectrum disorders.
Autism spectrum disorder (ASD) is a complex and prevalent neurodevelopmental disorder characterized by deficits in social communication and social interaction as well as repetitive behaviors. Alterations in function connectivity are widely recognized in recent electroencephalogram (EEG) studies. However, most studies have not reached consistent conclusions, which could be due to the developmental nature and the heterogeneity of ASD. Here, EEG coherence analysis was used in a cohort of children with ASD (n = 13) and matched typically developing controls (TD, n = 15) to examine the functional connectivity characteristics in long-distance and short-distance electrode pairs. Subsequently, we explore the association between the connectivity strength of coherence and symptom severity in children with ASD. Compared with TD group, individuals with ASD showed increased coherence in short-distance electrode pairs in the right temporal-parietal region (delta, alpha, beta bands), left temporal-parietal region (all frequency bands), occipital region (theta, alpha, beta bands), right central-parietal region (delta, alpha, beta bands), and the prefrontal region (only beta band). In the long-distance coherence analysis, the ASD group showed increased coherence in bilateral frontal region, temporal region, parietal region, and frontal-occipital region in alpha and beta bands. The strength of such connections was associated with symptom severity. Our study indicates that abnormal connectivity patterns in neuroelectrophysiology may be of critical importance to acknowledge the underlying brain mechanism.


A Survey to Assess Agreement Between Pelvic Surgeons on the Outcome of Examination Under Anesthesia for Lateral Compression Pelvic Fractures.
To assess agreement among pelvic surgeons regarding the interpretation of examination under anesthesia (EUA), the methodology by which EUA should be performed, and the definition of a positive examination. Survey. Ten patients who presented to our Level 1 trauma center with a pelvic ring injury were selected as clinical vignettes. Vignettes were distributed to 15 experienced pelvic surgeons. Examination under anesthesia. Agreement regarding pelvic fracture stability (defined as >80% similar responses), need for surgical fixation, definition of an unstable EUA, and method of performing EUA. There was agreement that a pelvic fracture was stable or unstable in 8 (80%) of 10 cases. There was agreement that fixation was required or not required in 6 (60.0%) of 10 cases. Seven (46.7%) surgeons endorsed performing a full 15-part EUA, whereas the other 8 (53.3%) used an abbreviated or alternative method. Eight (53.3%) surgeons provided a definition of what constitutes a positive EUA, whereas the remaining 7 did not endorse adhering to a strict definition. Pelvic surgeons generally agree on what constitutes a positive or negative EUA but not necessarily the implications of a positive or negative examination. There is no clear consensus among surgeons regarding the method of performing EUA nor regarding the definition of a positive EUA. Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Saccharomyces cerevisiae RAD53 (CHK2) but not CHK1 is required for double-strand break-initiated SCE and DNA damage-associated SCE after exposure to X rays and chemical agents.
Saccharomyces cerevisiae RAD53 (CHK2) and CHK1 control two parallel branches of the RAD9-mediated pathway for DNA damage-induced G(2) arrest. Previous studies indicate that RAD9 is required for X-ray-associated sister chromatid exchange (SCE), suppresses homology-directed translocations, and is involved in pathways for double-strand break repair (DSB) repair that are different than those controlled by PDS1. We measured DNA damage-associated SCE in strains containing two tandem fragments of his3, his3-Delta5' and his3-Delta3'::HOcs, and rates of spontaneous translocations in diploids containing GAL1::his3-Delta5' and trp1::his3-Delta3'::HOcs. DNA damage-associated SCE was measured after log phase cells were exposed to methyl methanesulfonate (MMS), 4-nitroquinoline 1-oxide (4-NQO), UV, X rays and HO-induced DSBs. We observed that rad53 mutants were defective in MMS-, 4-NQO, X-ray-associated and HO-induced SCE but not in UV-associated SCE. Similar to rad9 pds1 double mutants, rad53 pds1 double mutants exhibited more X-ray sensitivity than the single mutants. rad53 sml1 diploid mutants exhibited a 10-fold higher rate of spontaneous translocations compared to the sml1 diploid mutants. chk1 mutants were not deficient in DNA damage-associated SCE after exposure to DNA damaging agents or after DSBs were generated at trp1::his3-Delta5'his3-Delta3'::HOcs. These data indicate that RAD53, not CHK1, is required for DSB-initiated SCE, and DNA damage-associated SCE after exposure to X-ray-mimetic and UV-mimetic chemicals.


USP7 promotes the osteoclast differentiation of CD14+ human peripheral blood monocytes in osteoporosis via HMGB1 deubiquitination.
Abnormal osteoclast and osteoblast differentiation is an essential pathological process in osteoporosis. As an important deubiquitinase enzyme, ubiquitin-specific peptidase 7 (USP7) participates in various disease processes through posttranslational modification. However, the mechanism by which USP7 regulates osteoporosis remains unknown. Herein, we aimed to investigate whether USP7 regulates abnormal osteoclast differentiation in osteoporosis. The gene expression profiles of blood monocytes were preprocessed to analyze the differential expression of USP genes. CD14+ peripheral blood mononuclear cells (PBMCs) were isolated from whole blood collected from osteoporosis patients (OPs) and healthy donors (HDs), and the expression pattern of USP7 during the differentiation of CD14+ PBMCs into osteoclasts was detected by western blotting. The role of USP7 in the osteoclast differentiation of PBMCs treated with USP7 siRNA or exogenous rUSP7 was further investigated by the F-actin assay, TRAP staining and western blotting. Moreover, the interaction between high-mobility group protein 1 (HMGB1) and USP7 was investigated by coimmunoprecipitation, and the regulation of the USP7-HMGB1 axis in osteoclast differentiation was further verified. Osteoporosis in ovariectomized (OVX) mice was then studied using the USP7-specific inhibitor P5091 to identify the role of USP7 in osteoporosis. The bioinformatic analyses and CD14+ PBMCs from osteoporosis patients confirmed that the upregulation of USP7 was associated with osteoporosis. USP7 positively regulates the osteoclast differentiation of CD14+ PBMCs in vitro. Mechanistically, USP7 promoted osteoclast formation by binding to and deubiquitination of HMGB1. In vivo, P5091 effectively attenuates bone loss in OVX mice. We demonstrate that USP7 promotes the differentiation of CD14+ PBMCs into osteoclasts via HMGB1 deubiquitination and that inhibition of USP7 effectively attenuates bone loss in osteoporosis in vivo.The translational potential of this article:The study reveals novel insights into the role of USP7 in the progression of osteoporosis and provides a new therapeutic target for the treatment of osteoporosis.


Use of the contralateral subclavian vein for placement of atrial electrodes in chronically VVI paced patients.
Two patients with documented pacemaker syndrome were referred for AV sequential pacing and were found to have inaccessible venous systems on the side of their original transvenous pacemaker placement. The contralateral subclavian vein was subsequently catheterized with an atrial electrode using the sheath-set technique. Then the proximal aspect of the atrial endocardial lead was tunneled to the original pacemaker pocket. Once accomplished, both (atrial and ventricular) leads were connected to an AV sequential pulse generator. The united pulse generator and lead were reinserted in the original pacemaker pocket.


The spatial extent of excitatory and inhibitory zones in the receptive field of superficial layer hypercomplex cells.
1. An investigation has been made of the extent of inhibitory and excitatory components in the receptive field of superficial layer hypercomplex cells in the cat's striate cortex and the relation of the components to the length preference exhibited by these cells.2. Maximal responses were produced by an optimal length stimulus moving through a restricted region of the receptive field. The length of this receptive field region was less than the total length of the excitatory zone as mapped with a very short slit. Slits of similar length to the excitatory zone produced a smaller response than an optimal length slit.3. An increase of slit length so that it passed over receptive field regions either side of the excitatory zone resulted in an elimination of the response. When background discharge levels were increased by the iontophoretic application of D, L-homocysteic acid slits of this length were observed to produce a suppression of the resting discharge as they passed over the receptive field. They did not modify the resting discharge level when it was induced by the iontophoretic application of the GABA antagonist bicuculline. This data is taken to indicate that long slits activate a powerful post-synaptic inhibitory input to the cell.4. Maximal inhibitory effects were only observed if the testing slit passed over the receptive field centre. That is slits with a gap positioned midway along their length so as to exclude the optimal excitatory response region surprisingly tended to produce excitatory effects rather than the expected inhibitory effects. It appears that simultaneous stimulation of the receptive field centre is a precondition for the inhibitory effect of stimulation of regions either side of the excitatory zone to be activated.5. It is suggested that the interneurones mediating the inhibitory input to the superficial layer hypercomplex cells are driven both by cells in adjacent hypercolumns with receptive fields spatially displaced to either side of the excitatory zone and by cells in the same column, optimal inhibitory effects only being achieved when both sets of input to the interneurone are activated.


Antioxidant supplementation during treatment of outpatient dogs with parvovirus enteritis ameliorates oxidative stress and attenuates intestinal injury: A randomized controlled trial.
A prospective randomized controlled clinical study was conducted to determine whether antioxidant supplementation as an adjunct therapy alters hemogram, oxidative stress, serum intestinal fatty acid binding protein-2 (IFABP-2) level, fecal viral load, clinical score (CS) and survivability in outpatient canine parvovirus enteritis (CPVE) dogs. The dogs with CPVE were randomized to one of the five treatment groups: supportive treatment (ST) alone, ST with N-acetylcysteine (ST+NAC), resveratrol (ST+RES), coenzyme Q10 (ST+CoQ10) or ascorbic acid (ST+AA). The primary outcome measures were reduction of CS and fecal HA titre, and enhancement of survivability. Secondary outcome measures were reduction of oxidative stress indices and IFABP-2 level from day 0 to day 7. The mean CS and HA titre were significantly (P < 0.05) decreased from day 0 to 7 in ST and all antioxidant groups. The supplementations of NAC, RES and AA along with ST markedly (P < 0.05) reduced the concentrations of malondialdehyde, nitric oxide and IFABP-2 on day 7 as compared to ST alone. Additionally, NAC and RES supplementations markedly (P < 0.05) improved the total leukocyte count and neutrophil count in CPVE-affected dogs. NAC and RES could serve as better antioxidants for the amelioration of oxidative stress in CPVE but, the antioxidants did not confer any additional benefits in reduction of CS, fecal HA tire, or survivability when compared with ST alone.


Bacteria rather than fungi mediate the chemodiversity of dissolved organic matter in a mudflat intertidal zone.
Dissolved organic matter (DOM) in natural ecosystems is intimately associated with microbial communities. However, it remains unclear whether the diversity patterns followed by microbes can be transmitted to DOM compounds. Considering the structural properties of DOM compounds and the roles of microbes in ecosystems, we hypothesized that bacteria tended to be more closely associated with DOM compounds than fungi. To test the above hypothesis and bridge this knowledge gap, the diversity patterns and ecological processes for the DOM compounds, and the bacterial and fungal communities in a mudflat intertidal zone were comparatively investigated. As a result, spatial scaling patterns followed by microbes, including the diversity-area and distance-decay relationships, were also observed for DOM compounds. Lipid-like and aliphatic-like molecules comprised the major DOM compounds associated with environmental factors. Both the alpha- and beta-chemodiversity of DOM compounds were significantly associated with the diversity of bacterial communities, but not fungal communities. Co-occurrence ecological network analysis suggested that DOM compounds were more frequently associated with bacteria than fungi. Further, consistent community assembly patterns were observed for DOM and bacterial communities, but not fungal communities. Integrating multiple lines of evidence, this study demonstrated that bacteria rather than fungi mediated the chemodiversity of DOM in the mudflat intertidal zone. This study elucidates the spatial patterns of complex dissolved organic matter (DOM) pools in the intertidal ecosystem, shedding light on the intricate relationship between DOM compounds and bacterial communities.


Fibered platinum coil: A novel option for the patients of hydrosalpinx with laparoscopic contradiction.
To investigate the feasibility of proximal tubal occlusion with fibered platinum coils in subfertile women with hydrosalpinx, and to observe the clinical outcomes of subsequent treatment with in vitro fertilization and embryo transfer (IVF-ET). A prospective study was carried out in a university-affiliated teaching hospital. 56 women with uni- or bilateral hydrosalpinx received fibered platinum coil placement before IVF-ET. The clinical pregnancy rate and live birth rate was evaluated. Data analysis was performed with SPSS version 22.0 (SPSS, Inc., Chicago, IL, USA), using two-sided test, and a p value < 0.05 was considered statistically significant. The study has been registered in the ClinicalTrials. gov with the number of NCT03395301. Successful placement was achieved in 106 fallopian tubes of 55 patients. The fibered platinum coils induced complete proximal occlusion in 52 out of 55 patients in the following 3-month HSG examination. In the 52 patients, 44 patients received following IVF-ET. The clinical pregnancy rate reached 60.5%(23/38)and live birth rate reached 60.87% (14/23) in patients less than 40 years old. Fibered platinum coil is a new, safe and valuable device for hysteroscopic tubal proximal occlusion in subfertile women with hydrosalpinx but with laparoscopic contradictions to improve the reproductive outcomes of IVF-ET. Capsule: Fibered platinum coil is a new, safe and valuable device for hysteroscopic tubal proximal occlusion in subfertile women with hydrosalpinx to improve the reproductive outcomes of in vitro fertilization and embryo transfer.


Embryonic stem cells as a source of differentiated neural cells for pharmacological screens.
The process of bringing a new pharmacologically active drug to market is laborious, time consuming, and costly. From drug discovery to safety assessment, new methods are constantly sought to develop faster and more efficient procedures to eliminate drugs from further investigation because of their limited effectiveness or high toxicity. Because in vitro cell assays are an important arm of this discovery process, it is therefore somewhat unsurprising that there is an emerging contribution of embryonic stem (ES) cell technology to this area. This technology utilizes the in vitro differentiation of ES cells into somatic cell target populations that, when coupled to the use of "lineage selection" protocols, allows for the production of infinite numbers of pure populations of the desired cells for both bioactivity and toxicological screens. Unlike the use of transformed cell lines, ES-derived cells remain karyotypically normal and therefore better reflect the potential responses of cells in vivo, and when selected are more homogeneous than those obtained using primary cultures. In this chapter we discuss the use of ES cell-derived somatic cells in pharmacological screens, with particular emphasis on neural cells, and describe the methods and protocols associated with the development of ES cell-derived neural cell assays.


Perceived influence of health status on sexual activity in RA patients: associations with demographic and disease-related variables.
To examine the prevalence of self-reported problems with sexual activity in patients with rheumatoid arthritis (RA), and associations with demographic and disease-related variables. Perceived levels of problems with sexual activity were addressed through question 15 of the Health-Related Quality of Life (HRQoL) instrument 15D. Disease-related variables were determined with the Visual Analogue Scale (VAS), the Arthritis Impact Measurement Scale (AIMS2), the Health Assessment Questionnaire (HAQ), and the Arthritis Specific Self-Efficacy (ASES) questionnaire. Data were available from 830 patients with RA 74% female, mean (SD) age 58.5 (14.2) years, disease duration 13.4 (10.3) years, HAQ score 0.98 (0.72). No impact on sexual activity was reported by 31%, little by 38%, considerable by 21%, 3% reported sexual activity as almost impossible, and 7% reported sexual activity as impossible. When dichotomized, the 'large impact' group had worse health status across all dimensions compared to the group with 'no/little impact' (p<0.001). In the multiple logistic regression analyses, perceived impact on sexual activity was associated with male vs. female gender [odds ratio (OR) 3.18, 95% confidence interval (CI) 2.05-4.94], age (youngest vs. oldest group) (OR 3.56, 95% CI 1.78-7.09), increased levels of fatigue (OR 1.01, 95% CI 1.0-1.02) and mental distress (OR 1.21, 95% CI 1.06-1.38), HAQ score (OR 2.46, 95% CI 1.78-3.39), and low self-efficacy regarding symptoms (OR 0.97, 95% CI 0.96-0.98). One-third of the RA patients reported that their health status considerably influenced their sexual activity. Higher levels of fatigue, mental distress, functional limitations, lower levels of self-efficacy, and male gender were independently associated with perceived problems with sexual activity.


Fabry disease: an atypical presentation.
Fabry disease is a rare X-linked recessive lysosomal storage disease. Patients typically have angiokeratomas distributed between the umbilicus and knees, painful crises of the hands and feet, and renal, ophthalmologic, and cardiac abnormalities. An 11-year-old boy presented with a 6-year history of widespread petechial-like lesions and painful crises of the hands and feet. On physical examination, he had numerous erythematous, nonblanching pinpoint macules and rare papules with an overlying crust. These lesions were widely distributed on his trunk, palms, and soles, while sparing the area between the umbilicus and knees. Histologic evaluation of one of these lesions found several dilated, blood-filled vessels in the upper dermis beneath a thinned epidermis. The patient also had markedly decreased alpha galactosidase A levels. Although the distribution of the angiokeratomas was atypical, the clinical and histologic findings were consistent with a diagnosis of Fabry disease.


Analysis of thoracoscopy in trauma.
The role of video-assisted thoracic surgery (VATS) in trauma has yet to be established. Up to the time of this writing, reviews of thoracoscopy in trauma have been primarily descriptive rather than analytic. This article analyzes the results of thoracoscopy (nonvideo and VATS) in trauma. Analysis was done by reviewing 28 nonoverlapping studies since the introduction of thoracoscopy in 1910, with a combined total of more than 500 patients. Diagnostically, thoracoscopy has been used primarily to evaluate diaphragmatic injury, continued chest tube bleeding, and suspected cardiac injury. Thoracoscopy has a 98% (188/191 patients) accuracy rate in diagnosing diaphragmatic injuries. Therapeutically, thoracoscopy has been used primarily to control chest tube bleeding, evacuate retained hemothoraces, and evacuate empyemas. Thoracoscopy is 90% (89/99 patients) effective in evacuating retained hemothoraces, 86% (19/22 patients) effective in evacuating empyemas, and 82% (33/40 patients) effective in controlling chest tube bleeding. Thoracoscopy benefits include preventing 62% (323/514) of trauma patients from having a thoracotomy or laparotomy. Risks include a 2% (11/534 patients) procedure-related complication rate and a 0.8% (4/471 patients) missed injury rate. Technical failure rates are 10% (10/99 patients) and 4% (7/199 patients) in evacuation of retained hemothoraces and evaluation of diaphragmatic injuries, respectively. Analysis suggests that thoracoscopy (nonvideo and VATS) can be applied safely and effectively in the care of the injured patient.


Histopathological aid at the diagnosis of the Ehlers-Danlos syndrome, gravis and mitis types.
The Ehlers-Danlos syndrome is commonly divided into at least 8 types according to clinical, genetic, and biochemical aspects. We propose histological criteria that would permit a more precise diagnosis of the gravis and mitis types. In the gravis type, collagen bundles are thin and rare in the dermis and hypodermal septae; in polarized light, they are less refringent than in normal skin. This is associated with an increase in the relative proportion of elastic fibers. In the mitis type, the looseness of the collagen network is much less evident; elastic fibers are not in excess but irregular in size, shape, distribution, and orientation.


Celiac disease in monozygous twin boys. Asynchronous presentation.
A 13-year-old boy presented when his weight gain fell behind that of his monozygous twin brother. Following investigation, he was found to have gluten-sensitive enteropathy on jejunal biopsy. Investigation of his symptom-free brother showed biopsy evidence of the condition with changes similar to those of the clinically affected boy. Following treatment with a gluten-free diet, the boys achieved a similar weight after 15 months.


Structural basis of mapping the spontaneous mutations with 5-flurouracil in uracil phosphoribosyltransferase from Mycobacterium tuberculosis.
Tuberculosis (TB) remains the second leading cause of death from an infectious disease globally, despite the incessant efforts to control it. Research and development into new TB medicines is imperative for effective TB control; however, new strategies for the rational use of existing drugs, such as through the identification of new drug targets, could also significantly enhance this process. Key enzymes involved in the essential metabolic and regulatory pathways are usually sought in the pursuit of potential drug targets. Uracil phosphoribosyltransferase (UPRT) is a key salvage pathway enzyme in the synthesis of uridine 5'-monophosphate (UMP) and a probable target of 5-fluorouracil (5-FU) in Mycobacterium tuberculosis (Mtb). To date, there is no structure available for UPRT from Mtb (MtUPRT) that would assist in the identification of appropriate inhibitors for the enzyme. Here we report the structure of MtUPRT along with its spontaneous mutational studies in the presence of 5-FU. We further mapped these four single nucleotide polymorphisms (SNPs) onto the MtUPRT structure, with two residues found to be conserved among the MtUPRT homologs. Notably, none of these SNPs are located in the 5-FU binding pocket. However, the mutants harboring these mutations showed increased MICs (minimum inhibitory concentration) as compared to wild type strains. The present study will aid in the screening of inhibitors of MtUPRT and thus assist in TB drug design and development.


Sleep duration and timing in obsessive-compulsive disorder (OCD): evidence for circadian phase delay.
To investigate potential delays in endogenous melatonin in individuals with obsessive-compulsive disorder (OCD). First, data are presented for 15 individuals with OCD and matched healthy controls. Next, nine additional participants with OCD who did not have matched controls were added, resulting in a sample of 24 individuals with OCD. All participants were assessed for sleep and circadian rhythm disturbance. Dim light melatonin onset (DLMO) was derived from salivary melatonin and was used in conjunction with sleep diaries, interview measures, and questionnaires. A subset of the OCD group (n = 16) also used actigraphy. In sum, 42% percent (10/24) of the patients with OCD met the criteria for delayed sleep-wake phase disorder (DSWPD) in comparison to 0% in the control sample. DLMO was significantly later in individuals with OCD compared to controls. DLMO and bedtime were not significantly associated with the severity of obsessive-compulsive symptoms or negative affect. Replication of the findings presented herein, particularly the DLMO results, is warranted. Further, there are now three studies showing that nearly ½ of individuals with OCD meet criteria for a DSWPD. Future studies can explore the mechanisms underlying these connections and the implications of this comorbidity. These findings may increase our understanding of OCD and inform future interventions.


Cytochemical comparison of immunologically characterized human leukaemia/lymphoma cell lines representing different levels of maturation.
Forty-seven human leukaemia/lymphoma cell lines belonging to myelocytic, monocytic, non-T/non-B, T-, and B-lineage and representing different levels of maturation as well as fresh cells from normal and leukaemic subjects were examined for immunological markers and cytochemically for acid phosphatase, alkaline phosphatase, alpha-naphthyl acetate esterase (pH 5.8 and 8.0), alpha-naphthyl butyrate esterase (pH 5.8 and 8.0), non-specific esterase, chloroacetate esterase, chymotrypsin-like protease, deoxyribonuclease II, beta-glucuronidase, sudan black, and periodic acid Schiff's staining. Strong sudan black, nonspecific esterase, and chloroacetate esterase reaction was obtained only for myelocytic and monocytic cell lines with the reaction intensity increasing progressively in more mature cells. Focal acid phosphatase reaction like T-ALL was found in all T-ALL cell lines, whereas myeloid/monocytoid lines had semicircular distribution and B-cell lines cytoplasmic distribution of activity. Acid phosphatase activity appeared to decline with maturation along both myeloid and T-cell lineage. High activity of alpha-naphthyl acetate esterase and alpha-naphthyl butyrate esterase both at pH 5.8 and 8.0 and of beta-glucuronidase was found in myeloid/monocytoid lines although both B- and T-cell lines in contrast to peripheral blood B-cells also had significant esterase activity. alpha-Naphthyl butyrate esterase activity declined with increasing cell maturation along myeloid lineage. Except for weak activity in two B-cell lines alkaline phosphatase was not detected in any cell lines. Monocyte esterase activity was inhibited by sodium fluoride whereas acid phosphatase, only from hairy cell leukaemia line, was resistant to L-tartarate. Although periodic acid Schiff's staining could not distinguish myeloid, T-, B-, or non-T/non-B cell lines it gave characteristic reaction (large number of coarse granules against a clear background forming a ring around the nucleus) with erythroblastic leukaemia cell line and along myeloid series its intensity increased in more mature cells. Deoxyribonuclease II and chymotrypsin-like protease staining were not discriminatory. The results of this study show that cytochemical staining characteristics of various leukaemia/lymphoma cell lines are comparable to those of corresponding cells from patients and that the intensity and pattern of expression of these activities are related to cell type and degree of cell maturation. These studies give further credence to the use of these cell lines in cell differentiation, differential drug cytotoxicity, and many other studies.


High-throughput transcriptome sequencing analysis provides preliminary insights into the biotransformation mechanism of Rhodopseudomonas palustris treated with alpha-rhamnetin-3-rhamnoside.
The purple photosynthetic bacterium Rhodopseudomonas palustris has been widely applied to enhance the therapeutic effects of traditional Chinese medicine using novel biotransformation technology. However, comprehensive studies of the R. palustris biotransformation mechanism are rare. Therefore, investigation of the expression patterns of genes involved in metabolic pathways that are active during the biotransformation process is essential to elucidate this complicated mechanism. To promote further study of the biotransformation of R. palustris, we assembled all R. palustris transcripts using Trinity software and performed differential expression analysis of the resulting unigenes. A total of 9725, 7341 and 10,963 unigenes were obtained by assembling the alpha-rhamnetin-3-rhamnoside-treated R. palustris (RPB) reads, control R. palustris (RPS) reads and combined RPB&RPS reads, respectively. A total of 9971 unigenes assembled from the RPB&RPS reads were mapped to the nr, nt, Swiss-Prot, Gene Ontology (GO), Clusters of Orthologous Groups (COGs) and Kyoto Encyclopedia of Genes and Genomes (KEGG) (E-value <0.00001) databases using BLAST software. A total of 3360 unique differentially expressed genes (DEGs) in RPB versus RPS were identified, among which 922 unigenes were up-regulated and 2438 were down-regulated. The unigenes were mapped to the KEGG database, resulting in the identification of 7676 pathways among all annotated unigenes and 2586 pathways among the DEGs. Some sets of functional unigenes annotated to important metabolic pathways and environmental information processing were differentially expressed between the RPS and RPB samples, including those involved in energy metabolism (18.4% of total DEGs), carbohydrate metabolism (36.0% of total DEGs), ABC transport (6.0% of total DEGs), the two-component system (8.6% of total DEGs), cell motility (4.3% of total DEGs) and the cell cycle (1.5% of total DEGs). We also identified 19 transcripts annotated as hydrolytic enzymes and other enzymes involved in ARR catabolism in R. palustris. We present the first comparative transcriptome profiles of RPB and RPS samples to facilitate elucidation of the molecular mechanism of biotransformation in R. palustris. Furthermore, we propose two putative ARR biotransformation mechanisms in R. palustris. These analytical results represent a useful genomic resource for in-depth research into the molecular basis of biotransformation and genetic modification in R. palustris.


Orally delivered fipronil-laced bait reduces juvenile blacklegged tick (Ixodes scapularis) burdens on wild white-footed mice (Peromyscus leucopus).
While the topical acaricidal treatment of rodent pathogen reservoirs has been readily explored over the past several decades, oral systemic acaricidal treatment is only recently gaining traction as an alternative approach to the management of ticks and tick-borne pathogens. Recent laboratory tests have shown promise in the effectiveness of this systemic strategy against the blacklegged tick (Ixodes scapularis) and a Canadian field evaluation was recently published, but no recent field data from the United States yet exist. With this research, we sought to field deploy a commercially available fipronil-laced bait (Kaput® Flea Control Bait, Scimetrics LLC., Wellington, CO, USA; 0.005% fipronil; Environmental Protection Agency Reg. No. 72500-28), in an alternate use targeting white-footed mice (Peromyscus leucopus) to determine bait acceptance and potential impacts to juvenile I. scapularis burdens. Bait was readily accepted by wild P. leucopus and other rodent reservoirs. An ad libitum distribution strategy as well as placing smaller volumes of fipronil-laced bait within individual Sherman traps both resulted in significant reductions (57-94%) in juvenile I. scapularis burdens as compared to control over two years. The oral delivery of systemic acaricides shows promise in reduction of I. scapularis burdens on P. leucopus and should be further explored to determine effectiveness on host-seeking tick abundances, associated pathogen infection, and potentially incorporated into integrated tick management programs.


Prevalence of type 2 inflammatory signatures and efficacy of dupilumab in patients with chronic rhinosinusitis with nasal polyps from two phase 3 clinical trials: SINUS-24 and SINUS-52.
This post hoc analysis of the international SINUS-24/-52 trials (NCT02912468/NCT02898454) aimed to assess dupilumab efficacy in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) according to different definitions of type 2 inflammatory signature. Six definitions of type 2 inflammation were used: ≥150 eosinophils/μL or total immunoglobulin E (IgE) ≥100 IU/mL with a coexisting type 2 condition; ≥150 eosinophils/μL or total IgE ≥100 IU/mL; ≥150 eosinophils/μL; ≥250 eosinophils/μL or total IgE ≥100 IU/mL; coexisting asthma or ≥300 eosinophils/μL; presence of a coexisting type 2 condition. Odds ratios (ORs; dupilumab vs. placebo) for achieving clinically meaningful improvement (≥1 point) from baseline to week 24 (pooled SINUS-24/-52) and week 52 (SINUS-52) were calculated for nasal polyp score (NPS; range 0-8), nasal congestion/obstruction score (NC; 0-3), and loss of smell score (LoS; 0-3). At baseline (n = 724), most patients displayed a type 2 inflammatory signature across definitions (64.2%-95.3%). At week 24, ORs for clinically meaningful improvement ranged from 11.9 to 14.9 for NPS across type 2 definitions, 6.5-9.6 for NC, and 12.2-17.8 for LoS (all p < 0.0001). OR ranges were similar or greater at week 52: 19.0-36.6, 7.6-12.1, and 9.2-33.5, respectively (all p < 0.0001). Most patients with CRSwNP in the SINUS study had type 2 inflammation. Dupilumab demonstrated robust efficacy across definitions of type 2 inflammation, consistent with its profile as an inhibitor of Interleukin-4 and Interleukin-13 signaling, key and central drivers of type 2 inflammation in CRSwNP. This study assessed type 2 inflammation prevalence and dupilumab efficacy in chronic rhinosinusitis with nasal polyps according to algorithm-defined type 2 inflammation Dupilumab efficacy was similar across all type 2 definitions.


Diagnostic Imaging of the Lower Respiratory Tract in Neonatal Foals: Radiography and Computed Tomography.
Diagnostic imaging plays an essential role in the diagnosis and monitoring of lower respiratory disease in neonatal foals. Radiography is most widely available to equine practitioners and is the primary modality that has been used for the characterization of respiratory disease in foals. Computed tomography imaging, although still limited in availability to the general practitioner, offers advantages over radiography and has been used diagnostically in neonatal foals with respiratory disease. Recognition of appropriate imaging protocols and patient-associated artifacts is critical for accurate image interpretation regardless of the modality used.


Quantitative morphology of endocrine cells in human fetal pancreas.
Sections of pancreas from human fetuses, 6-20 weeks gestation, were stained with immunoperoxidase for insulin (B cells), glucagon (A cells), pancreatic polypeptide or somatostatin (D cells). Morphometric analyses were performed on sections from head and tail regions of each fetus. No stained cells were found at 7 weeks. A, B, pancreatic polypeptide and D cells were found at 9 weeks in primitive islets or as isolated cells adjacent to duct cells. There was no relationship between the density of each endocrine cell type and fetal age, but there was a significant increase in the relative density (percentage total endocrine cells) of D cells from 10-20 weeks (p less than 0.01). The tail contained significantly more A cells (p less than 0.05) and less pancreatic polypeptide cells (p less than 0.01) than the head but similar densities of B and D cells. Lobules containing a high density of pancreatic polypeptide cells and few A cells were found in the posterior part of the head in six fetuses, aged 10-20 weeks.


Tetra-aqua-bis-(2,3-di-hydro-1,4-benzodioxine-2-carboxyl-ato)calcium(II).
The acid-base reaction of 1,4-benzodioxane 2-carb-oxy-lic acid with calcium carbonate furnished the centrosymmetric title compound, [Ca(C9H7O4)2(H2O)4], in which the metal ion is octa-hedrally coordinated by two monodentate 1,4-benzodioxane 2-carboxyl-ate ligands and four water mol-ecules. In the crystal, O-H⋯O and C-H⋯O hydrogen bonds link the mol-ecules into a three-dimensional network.


Endovascular repair for left common iliac artery occlusion following blunt trauma without associated bony injury: image in vascular surgery.
Common iliac artery injury (CIAI), commonly associated with pelvic fractures may present with a potentially fatal combination of haemorrhage and limb ischaemia. We report a case of isolated CIAI from blunt trauma without bony injury treated successfully using endovascular repair.


Transitions into and out of post-traumatic stress among children involved in the child welfare system.
To describe the transition patterns into and out of post-traumatic stress (PTS) for youth and identify social supports preceding these transitions. We used inhomogeneous, continuous-time, 1Markov Chain models to model transitions in and out of PTS using data from Waves 1, 3, 4, and 5 of the National Survey of Child and Adolescent Wellbeing (NSCAW I)-a longitudinal study of children who first had contact with the child welfare system between 1999 and 2000. Our analytic sample contained 915 individuals aged 11-17 years. We analyzed data in 2020. Youth with stronger peer relationships were less likely to transition into PTS (HR: 0.82; 95% CI [0.70-0.96]), and these individuals were also more likely to transition out of PTS (HR: 1.21; 95% CI [1.04, 1.42]). Youth with adult support were less likely to transition into PTS at any given time interval (HR: 0.37; 95% CI [0.17-0.78]), but adult support was not associated with the transition out of PTS. Strengthening peer relationships may help at-risk children both avoid PTS altogether and recover from PTS after its onset. Promoting adult support, however, may only be most effective when attempting to prevent PTS-onset.


Surgical management of velopharyngeal incompetence in velocardiofacial syndrome.
To analyze the results of surgery for velopharyngeal incompetence (VPI) in velocardiofacial syndrome. Prospective data collection, with randomized, blind assessment of speech and velopharyngeal function on lateral videofluoroscopy and nasendoscopy. Two-site, tertiary referral cleft unit. Forty-two consecutive patients with the 22q11 deletion underwent surgery for symptomatic VPI by a single surgeon. Intraoral examinations, lateral videofluoroscopy (+/- nasendoscopy) and intraoperative evaluation of the position of the velar muscles through the operating microscope. Based on these findings, either a radical dissection and retropositioning of the velar muscles (submucous cleft palate [SMCP repair]) or a Hynes pharyngoplasty (posterior pharyngeal wall augmentation pharyngoplasty) was performed. As anticipated, a proportion of patients undergoing SMCP repair subsequently required a Hynes. The aim of this staged approach was to maximize velar function, thereby enabling a less obstructive pharyngoplasty to be performed. Thus, there were three surgical groups for analysis: SMCP alone, Hynes alone, and SMCP+Hynes. Blind perceptual rating of resonance and nasal airflow; blind assessment of velopharyngeal function on lateral videofluoroscopy and nasendoscopy; and identification of predictive factors. Significant improvement in hypernasality in all three groups. The SMCP+Hynes group also showed significant improvement in nasal emission. There were significant improvements in the extended and resting velar lengths following SMCP repair and a trend toward increased velocity of closure. Depending on velopharyngeal anatomy and function, there is a role for SMCP repair, Hynes pharyngoplasty, and a staged combination of SMCP+Hynes, all of which are procedures with a low morbidity.


Validity of bone mineral density measurements in distal sites as an indicator of total bone mineral density in a group of pre-adolescent and adolescent women.
The study of bone mineral density (BMD) has received attention due to the importance of osteoporosis as a public health problem in Mexico. The objective of this study was to assess the validity of BMD measures in distal forearm and calcaneus with portable densitometers as indicators of BMD on other anatomic sites. We conducted a cross-sectional study with 219 women from 9 to 22 years of age in Cuernavaca, Morelos, Mexico. We measured BMD in central sites (the entire skeleton, excluding head, proximal femur, and lumbar spine) using dual X-ray absorptiometry (DXA) and in peripheral sites (distal forearm and calcaneus) using a portable densitometer with DXA technology. Measurements of height, weight, body composition, physical activity, and demographic characteristics were collected. Agreement of measurements of BMD was assessed using correlation and regression analysis, and the method proposed by Bland and Altman. Higher levels of BMD were found in total skeleton (0.88 g/cm(2)) than in calcaneus (0.48 g/cm(2)) and distal forearm (0.38 g/cm(2)) (p <0.05). Moderate-to-high positive correlation coefficients (all significant) (p <0.05) were found between BMD in distal forearm and calcaneus vs. central anatomic sites, ranging from r = 0.49 to r = 0.78. BMD was higher in central sites compared with distal forearm and calcaneus. Measurement of BMD in distal forearm and calcaneus with portable densitometers provided valid indicators of BMD in central anatomic sites among pre-adolescent and adolescent women in Mexico.


Foxa2 regulates the expression of Nato3 in the floor plate by a novel evolutionarily conserved promoter.
The development of the neural tube into a complex central nervous system involves morphological, cellular and molecular changes, all of which are tightly regulated. The floor plate (FP) is a critical organizing center located at the ventral-most midline of the neural tube. FP cells regulate dorsoventral patterning, differentiation and axon guidance by secreting morphogens. Here we show that the bHLH transcription factor Nato3 (Ferd3l) is specifically expressed in the spinal FP of chick and mouse embryos. Using in ovo electroporation to understand the regulation of the FP-specific expression of Nato3, we have identified an evolutionarily conserved 204 bp genomic region, which is necessary and sufficient to drive expression to the chick FP. This promoter contains two Foxa2-binding sites, which are highly conserved among distant phyla. The two sites can bind Foxa2 in vitro, and are necessary for the expression in the FP in vivo. Gain and loss of Foxa2 function in vivo further emphasize its role in Nato3 promoter activity. Thus, our data suggest that Nato3 is a direct target of Foxa2, a transcription activator and effector of Sonic hedgehog, the hallmark regulator of FP induction and spinal cord development. The identification of the FP-specific promoter is an important step towards a better understanding of the molecular mechanisms through which Nato3 transcription is regulated and for uncovering its function during nervous system development. Moreover, the promoter provides us with a powerful tool for conditional genetic manipulations in the FP.


Reversible control of reproduction in tom cats: medical options for manipulating libido and fertility.
There has been a growing interest in alternatives to surgery for controlling reproduction in tom cats, and the resultant medical options add to a practitioner's toolbox when handling these cases in clinical practice. It is important, however, that when suggesting these drugs, veterinarians have a good understanding of their mode of action, and their correct use and dosage. Breeders increasingly wish to be able to switch on/off the reproductive ability of their tom cats in a controlled manner. In addition, in small animal medicine, there has been concern from some academics, and a growing number of pet cat owners, about potential long-term effects of surgical sterilisation. Further, for some cats surgical castration may not be possible due to health conditions that mean anaesthesia is unsafe. In all of these scenarios, medical alternatives to surgery can prove useful. No special equipment or technical skills are required. A good knowledge of the medical alternatives to surgical sterilisation for controlling reproduction in a tom, and making sure the patient is a suitable candidate, are, however, important for ensuring the cat's health during and after treatment and the owner's satisfaction. This review is aimed principally (but not exclusively) at veterinary practitioners working with cat breeders who seek a temporary arrest in their tom cat's reproduction. It may also help practitioners with clients who would like an alternative to surgery or with cats where anaesthesia for surgical castration is not possible. Advances in reproductive feline medicine have resulted in improved knowledge of medical contraception. This review draws on scientific evidence-based papers that report on the mode of action, length of efficacy and potential side effects of different methods of medical contraception, as well as the authors' own clinical experience.


Neuroprotective effects of polysaccharide from Sparassis crispa on Alzheimer's disease-like mice: Involvement of microbiota-gut-brain axis.
Alzheimer's disease (AD) is an irreversible neurodegenerative disease that may cause neurotoxicity and imbalance in gut microbiota. A polysaccharide derived from Sparassis crispa-1 (SCP-1) acts as a neuroprotective agent in vitro. There is, however, no clarity on the mechanism responsible for SCP-1's neuroprotective effects against AD. In this study, C57BL/6J male mice were treated with D-galactose and AlCl3 to establish an animal model of AD, followed by treatment with SCP-1. As evidenced by behavioral tests and brain pathology, SCP-1 treatment ameliorated learning deficits and defective spatial recognition, reduced amyloidogenesis, and modulated the neurotransmitter levels (γ-aminobutyric acid, glutamate, and acetylcholine) in the brain of AD mice. The results of 16S rRNA sequencing revealed that SCP-1 reshaped the gut microbiota composition, especially by promoting the proliferation of butyrate-producing genera, such as Intestinaimonas, [Eubacterium] ventriosum group, Lachnospiraceae_UCG_010, and Lachnospiraceae_UCG_001, and suppressing the growth of inflammation-related bacteria (i.e., Escherichia/Shigella). Furthermore, SCP-1 significantly attenuated inflammation by reducing the levels of inflammatory cytokines, maintaining intestinal barrier function, inhibiting glial activation, and decreasing the expression of toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB). Collectively, our findings suggest that SCP-1 may prevent the development of AD via modulation of gut microbiota and suppression of inflammation, for a potential application in preventing or managing AD.


Clinical value of serum digoxin assays in outpatients: improvement by the standardization of blood sampling.
Everyday physical activity previously has been shown to affect serum digoxin concentrations. Standardized rest in the supine position increases outpatient serum digoxin levels 0% to 75%. The present study comprising 56 outpatients treated with digoxin was undertaken to elucidate the clinical importance of a standardized period of rest before collection of the blood sample. Blood samples were taken about 24 hours after the latest dose, before and after 2 hours of rest in the supine position. A careful clinical examination, including electrocardiogram (ECG) findings, systolic time intervals, and chest x-ray studies, was performed to identify adverse effects/intoxication or failure of digitalis treatment. Signs of failure of digitalis treatment occurred in 12% of the patients, with a serum digoxin concentration of 0.68 +/- 0.15 (mean +/- SD) nmol/L before rest and 0.85 +/- 0.22 nmol/L after rest. Eleven percent showed signs of adverse effects/intoxication, with serum digoxin concentrations of 1.70 +/- 0.70 nmol/L before rest and 2.08 +/- 0.80 nmol/L after rest. The serum digoxin concentrations of the adequately treated patients (77%) were 1.02 +/- 0.35 nmol/L before rest and 1.28 +/- 0.41 nmol/L after rest. The importance of standardized rest before blood sampling is illustrated by the fact that only one third of the patients without signs of adverse effects/intoxication or failure of digitalis treatment had serum digoxin concentrations within the therapeutic range most commonly used (1.2 to 2.6 nmol/L) without supine rest. If allowed to rest in the supine position before blood sampling, approximately 60% of the adequately treated patients had serum digoxin concentrations within this range.(ABSTRACT TRUNCATED AT 250 WORDS)


Pathological alterations in Syrian golden hamster lungs after passive exposure to cigarette smoke.
The effects of 2 types of research cigarettes, differing in their total smoke delivery and condensate, were examined as to their histopathological effects of Syrian golden hamster lungs. The animals were passively exposed to the total smoke of the cigarettes once a day, 5 days/week for 1 year. Experimental and control animals were killed one day after termination of exposure. Varying effects on the macrophages of pulmonary alveolar tissue were observed. Infiltration of lung tissue by "Brown cells" was a common pathological alteration. Qualitative and quantitative differences existed between the two cigarette groups with respect to the occurrence of such "Brown cell" clumps. The response of the lung tissue to smoke exposure would appear to be dependent upon the amount of mainstream total particulate matter (TPM), the amount of condensate, the time exposed and the number of cigarettes.


Thermodynamic investigation of nanoplastic aggregation in aquatic environments.
In this study, the aggregation behavior of polystyrene nanoplastics (PS NPs) in the absence or presence of oppositely charged particulate matters is systematically investigated for a wide range of electrolyte conditions. Herein, we used isothermal titration calorimetry combined with time-resolved dynamic light scattering to provide kinetic and thermodynamic insights into the NP aggregation. The thermodynamic profiles of homoaggregation and heteroaggregation were fit using an independent site and two independent sites models, respectively, demonstrating different interaction modes of both aggregation processes. We found that the contribution of solvation entropy was significant and variable in most cases, and this thermodynamic parameter was a large determinant of the thermodynamics of NP aggregation. Furthermore, the stability of PS NPs in natural water matrices was found to be correlated with ionic strength and the content of natural colloids (e.g., metal oxides and clay particles). These results point to the importance of considering the role of thermodynamic variables when studying the fate of NPs within various environmental conditions.


Endoscopic management of radio-opaque bile duct stones.
Majority of the bile duct stones (BDS) are radiolucent (RL) and are amenable to conventional endoscopic extraction techniques. There is no publication that specifically discusses the optimal management of radio-opaque (RO) BDS and makes a distinction from the strategy followed for RL BDS. Data of patients with BDS managed endoscopically from January 2009 till June 2015 were retrospectively reviewed. Diagnosis of RO stone was established during initial fluoroscopy, just prior to obtaining a cholangiogram. Endoscopic retrograde cholangiopancreatography (ERCP) was done using therapeutic duodenoscope. Stone extraction was attempted initially using conventional techniques. Balloon sphincteroplasty or mechanical lithotripsy (ML) or both were done if conventional techniques failed. Cholangioscopy-guided intracorporeal holmium laser lithotripsy (LL) was done when all the above techniques failed. Fifteen patients were found to have RO stones in the bile duct during the study period. ERCP was successful in all patients. Discrepancy of the stone size in relation to the lower CBD diameter was seen in eight patients (53.34 %). Stone extraction with conventional techniques was successful in 2/15 patients (13 %). Successful controlled radial expansion (CRE) balloon sphincteroplasty/ML was possible in 5/15 patients (33 %). Cholangioscopy guided LL was done in eight patients (53.34 %) with successful pulverization of RO BDS (100 %). RO bile duct stones provide unique challenges for endoscopic management with success of conventional techniques in only about half of them (46 %). RO stones detected on fluoroscopy are extremely hard and difficult to crush with lithotripsy basket probably due to high calcium content. Cholangioscopy guided LL provides an excellent alternative management strategy.


Revised Protocol for Secondary Prevention of Congenital Cytomegalovirus Infection With Valaciclovir Following Infection in Early Pregnancy.
A previous randomized placebo-controlled study found valaciclovir to be effective in reducing the rate of vertical cytomegalovirus transmission from mother to fetus. The better results in women infected in the first trimester compared to the periconception period were attributed to the timing of treatment. The aim of the present study was to evaluate valaciclovir efficacy in this setting using a revised protocol. All pregnant women treated with valaciclovir in 2020-2022 who met the same criteria as in the original study were identified retrospectively from the database of the same medical center. Treatment, however, was initiated earlier: up to 9 weeks or 8 weeks from the presumed time of infection in women infected in the periconception period or the first trimester, respectively. The primary endpoint was rate of vertical cytomegalovirus transmission. Results were compared with the placebo arm in the previous study. Among 178 women who completed valaciclovir treatment, amniocentesis was positive for cytomegalovirus in 14 women (7.9%), significantly (P < .001) lower compared with 14 of 47 (30%) in the placebo arm in the previous study. The proportion of positive amniocentesis in the valaciclovir was significantly lower than the placebo arm both among women infected in the first trimester (14/119 vs 11/23; odds ratio [OR] = 0.15; 95% confidence interval [CI]: .05-.45, P < .001), as well as among those infected in the periconception period (0/59 vs 3/24, OR = 0; 95% CI 0-.97, P = .02). This study provides further evidence of the efficacy of valaciclovir in preventing vertical transmission of cytomegalovirus after primary maternal infection. Efficacy is improved with earlier treatment.


Follow-up of a flatulent patient.
This paper describes a low-flatulence diet developed by an extremely flatulent patient. Based on meticulous recording of each passage of flatus, the patient employed an elimination diet to determine what foods were responsible for his gas production. The diet reduced the frequency of his gas passage from 34 +/- 7 to 17 +/- 5 times per day (normal: 14 +/- 6) and similar reductions were observed by two other flatulent patients during adherence to the diet. The rectal gas of each of these subjects largely consisted of two gases (CO2 and H2) which result from bacterial fermentation of carbohydrates. The diet, which is low in lactose and wheat products, presumably minimizes the quantity of carbohydrates delivered to the colonic bacteria.


WITHDRAWN: Immunogenicity and safety of HCV E1E2 peptide vaccine in chronically HCV-infected patients who did not respond to interferon based therapy.
This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.


Treatment Advances in Spinal Muscular Atrophy.
Spinal muscular atrophy (SMA) is a genetic disorder of motor neurons in the anterior horns of the spinal cord and brainstem that results in muscle atrophy and weakness. SMA is an autosomal recessive disease linked to deletions of the SMN1 gene on chromosome 5q. Humans have a duplicate gene (SMN2) whose product can mitigate disease severity, leading to the variability in severity and age of onset of disease, and is therefore a target for drug development. Advances in preclinical and clinical trials have paved the way for novel therapeutic options for SMA patients, including many currently in clinical trials. In 2016, the first treatment for SMA has been approved in the USA, an antisense oligonucleotide that increases full-length protein product derived from SMN2. The approval of a first treatment for SMA and the rapid advances in clinical trials provide the prospect for multiple approaches to disease modification. There are several other promising therapeutics in different stages of development, based on approaches such as neuroprotection, or gene therapy.


Knowledge and skill retention of in-service versus preservice nursing professionals following an informal training program in pediatric cardiopulmonary resuscitation: a repeated-measures quasiexperimental study.
Our objective was to compare the impact of a training program in pediatric cardiopulmonary resuscitation (CPR) on the knowledge and skills of in-service and preservice nurses at prespecified time points. This repeated-measures quasiexperimental study was conducted in the pediatric emergency and ICU of a tertiary care teaching hospital between January and March 2011. We assessed the baseline knowledge and skills of nursing staff (in-service nurses) and final year undergraduate nursing students (preservice nurses) using a validated questionnaire and a skill checklist, respectively. The participants were then trained on pediatric CPR using standard guidelines. The knowledge and skills were reassessed immediately after training and at 6 weeks after training. A total of 74 participants-28 in-service and 46 preservice professionals-were enrolled. At initial assessment, in-service nurses were found to have insignificant higher mean knowledge scores (6.6 versus 5.8, P = 0.08) while the preservice nurses had significantly higher skill scores (6.5 versus 3.2, P < 0.001). Immediately after training, the scores improved in both groups. At 6 weeks however, we observed a nonuniform decline in performance in both groups-in-service nurses performing better in knowledge test (10.5 versus 9.1, P = 0.01) and the preservice nurses performing better in skill test (9.8 versus 7.4, P < 0.001). Thus, knowledge and skills of in-service and preservice nurses in pediatric CPR improved with training. In comparison to preservice nurses, the in-service nurses seemed to retain knowledge better with time than skills.


Impact of concurrent androgen deprivation on fiducial marker migration in external-beam radiation therapy for prostate cancer.
To determine the extent of gold fiducial marker (FM) migration in patients treated for prostate cancer with concurrent androgen deprivation and external-beam radiation therapy (EBRT). Three or 4 gold FMs were implanted in 37 patients with prostate adenocarcinoma receiving androgen deprivation therapy (ADT) in conjunction with 70-78 Gy. Androgen deprivation therapy was started a median of 3.9 months before EBRT (range, 0.3-12.5 months). To establish the extent of FM migration, the distance between each FM was calculated for 5-8 treatments once per week throughout the EBRT course. For each treatment, the distance between FMs was compared with the distance from the digitally reconstructed radiographs generated from the planning CT. A total of 281 treatments were analyzed. The average daily migration was 0.8 ± 0.3 mm, with distances ranging from 0.2 mm-2.6 mm. Two of the 281 assessed treatments (0.7%) showed migrations >2 mm. No correlation between FM migration and patient weight or time delay between ADT and start of EBRT was found. There was no correlation between the extent of FM migration and prostate volume. This is the largest report of implanted FM migration in patients receiving concomitant ADT. Only 0.7% of the 281 treatments studied had significant marker migrations (>2 mm) throughout the course of EBRT. Consequently, the use of implanted FMs in these patients enables accurate monitoring of prostate gland position during treatment.


Effects of pretreatment methods on biomethane production kinetics and microbial community by solid state anaerobic digestion of sugarcane trash.
Solid state anaerobic digestion (SS-AD) of lignocellulose is effective in improving biomethane productivity but is limited by low biomass digestibility and lack of substrate-specific working microorganisms. In this study, the effects of different pretreatment methods on biomethane production by SS-AD of sugarcane trash were studied. The biomethane production, fitted to a modified Gompertz's model, predicted a maximum methane yield of 214.2 L/kg volatile solids (VS) and productivity of 6.9 L/kg VS/day from KOH-pretreated trash, respectively. Microbial community analysis showed that bacterial community was significantly associated with volatile acids and pretreatment types while archaeal community was significantly associated with methane yield. Microbial community dynamics was revealed in SS-AD. Main genera related to pretreatment method were identified and discussed. This study generated important information on SS-AD of lignocellulosic biomass pretreated by different methods, which is useful for developing bioaugmentation strategies to improve biomethane production by SS-AD.


Tracing and separating plasma components causing matrix effects in hydrophilic interaction chromatography-electrospray ionization mass spectrometry.
Matrix effects on electrospray ionization were investigated for plasma samples analysed by hydrophilic interaction chromatography (HILIC) in gradient elution mode, and HILIC columns of different chemistries were tested for separation of plasma components and model analytes. By combining mass spectral data with post-column infusion traces, the following components of protein-precipitated plasma were identified and found to have significant effect on ionization: urea, creatinine, phosphocholine, lysophosphocholine, sphingomyelin, sodium ion, chloride ion, choline and proline betaine. The observed effect on ionization was both matrix-component and analyte dependent. The separation of identified plasma components and model analytes on eight columns was compared, using pair-wise linear correlation analysis and principal component analysis (PCA). Large changes in selectivity could be obtained by change of column, while smaller changes were seen when the mobile phase buffer was changed from ammonium formate pH 3.0 to ammonium acetate pH 4.5. While results from PCA and linear correlation analysis were largely in accord, linear correlation analysis was judged to be more straight-forward in terms of conduction and interpretation.


Initial multicenter community robotic lobectomy experience: comparisons to a national database.
In pulmonary lobectomy, video-assisted thoracoscopic surgery (VATS) offers advantages compared with open thoracotomy. However, various issues have limited its adoption, especially in community settings. Single surgeon studies suggest that completely portal robotic lobectomy (CPRL) may address such limitations. This multicenter study evaluates early CPRL experience in 6 community cardiothoracic surgeons' practices. Perioperative data from each surgeon's initial 20, consecutive and unselected cases of CPRL were retrospectively gathered (total n = 120) and compared with the 2009 and 2010 Society of Thoracic Surgeons database for VATS (n = 4,612) and open (n = 5,913) lobectomy. The χ(2) and t test procedures were used and significance was defined at the 95% confidence level (p < 0.05). One hundred sixteen lobectomies (96.7%) were completed robotically with a conversion rate of 3.3%. Preoperative patient characteristics were comparable across the CPRL, VATS, and open groups. The CPRL was equivalent to VATS on all intraoperative and postoperative outcomes, and resulted in significantly lower postoperative blood transfusion rates (0.9% vs 7.8%; p = 0.002), air leaks greater than 5 days (5.2% vs 10.8%; p = 0.05), chest tube duration (3.2 days vs 4.8 days; p < 0.001), and length of stay (4.7 days vs 7.3 days; p < 0.001) when compared with open. For these outcomes, results trended favorably for CPRL over VATS. This early CPRL experience reveals a minimally invasive lobectomy technique that is safe and reproducible in varied practice settings. Outcomes were equivalent between CPRL and VATS, trending in favor of robotics. The CPRL was superior in several measures compared with open. The absence of patient selection and low conversion rates suggest a broad applicability of this technique.


Treatment with chitin microparticles is protective against lung histopathology in a murine asthma model.
Chitin, a natural polysaccharide extracted from shrimp, is a potent T and B cell adjuvant when delivered in the form of chitin microparticles and can shift a polarized T-helper type 2 (Th2) immune response towards a Th1 response. We investigated the beneficial effects of the intranasal application of chitin microparticles in newborn mice before and after the establishment of a model of allergic asthma. Mice were grouped as asthma (A), primary prevention (PP), treatment (T), primary prevention+treatment (PPT) and control (C) groups. All mice except controls were sensitized with ovalbumin intraperitoneally and challenged intratracheally to establish the asthma model. Mice in the PP and PPT groups received chitin microparticles intranasally during the newborn period before sensitization. Mice in the PPT and T groups received intranasal chitin microparticles after challenge. Airway histopathology was evaluated in all groups. All of the airway histopathologic parameters of small and medium-sized airways of the T and PPT groups were significantly ameliorated when compared with the asthma model group. In the large airways, thicknesses of basement membrane, epithelium and subepithelial smooth muscle layers of the PPT group and basement membrane thicknesses of the T group were also significantly lower compared with the asthma model group. Comparison of the PP group with the asthma model group revealed significantly reduced goblet cell numbers and significantly reduced epithelial and basement membrane thicknesses in small and medium airways, in addition to significantly reduced basement membrane thicknesses in the medium-sized airways. Intranasal application of microgram quantities of chitin microparticles had a beneficial effect in preventing and treating histopathologic changes in the airways of asthmatic mice.


Hantavirus RNA in saliva from patients with hemorrhagic fever with renal syndrome.
Hantaviruses cause 2 zoonotic diseases, hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome. Infection is usually initiated after inhalation of virus-contaminated rodent excreta. In addition to the zoonotic infection route, growing evidence suggests person-to-person transmission of Andes virus. For this reason, we studied whether saliva from HFRS patients contained hantavirus. During an outbreak in northern Sweden of nephropathia epidemica (NE), a milder form of hemorrhagic fever with renal syndrome, we collected saliva and plasma from 14 hospitalized NE patients with verified Puumala virus (PUUV) infection. PUUV RNA was detected in saliva from 10 patients (range 1,530-121,323 PUUV RNA copies/mL) by quantitative reverse transcription-PCR. The PUUV S-segment sequences from saliva and plasma of the same patients were identical. Our data show that hantavirus RNA could be detected in human saliva several days after onset of disease symptoms and raise the question whether interhuman transmission of hantavirus may occur through saliva.


Immunoglobulin E responses to diphtheria and tetanus toxoids after booster with aluminium-adsorbed and fluid DT-vaccines.
Immunoglobulin E responses to diphtheria and tetanus toxoids were investigated in pre- and postbooster samples of 104 children given, at 10 years of age, a DT booster with either an adsorbed (n = 51) or a non-adsorbed, fluid vaccine (n = 53). Vaccination with adsorbed DT is part of a national immunisation programme and represents the first regular booster given to these children, primarily immunised with three doses of adsorbed DT at age 3-6 months. The vaccines, with a content of 30 Lf of diphtheria toxoid and 7.5 Lf of tetanus toxoid per millilitre, were given for booster in a dose of 0.25 ml as a deep subcutaneous injection. In the prebooster samples, 3 and 14% had measurable IgE to diphtheria and tetanus, respectively. These rates rose to 94 and 92% in the postbooster samples, respectively. The median (range) of IgE to tetanus among recipients of the adsorbed vaccine was 0.59 PRU ml-1 (< 0.1-17.5), as compared to 0.27 (< 0.1-8.22) in the recipients of the fluid vaccine (p = 0.027). The median IgE response to diphtheria toxoid in the whole group was 1.8 (< 0.1-17.5), with no significant difference between the two vaccines (p = 0.76). There was no correlation between the IgE and IgG responses (r < 0.07, p > 0.5) but the two IgE responses as well as the ratios of IgG/IgE showed strong correlations (r > 0.7, p < 0.001). The study thus revealed unexpectedly high rates of IgE responses to diphtheria and tetanus toxoids in a regular DT booster vaccination programme, which were associated to high rates of local side effects.(ABSTRACT TRUNCATED AT 250 WORDS)


Scoring system to determine need for balloon atrial septostomy for restrictive interatrial communication in infants with hypoplastic left heart syndrome.
Restrictive interatrial communication (IAC) causes morbidity and mortality in infants with hypoplastic left heart syndrome awaiting cardiac transplantation. We sought to create a scoring system, based on echocardiographic and clinical findings, to serve as a guide for determining the need for balloon atrial septostomy (BAS). We retrospectively reviewed echocardiograms of 44 infants with hypoplastic left heart syndrome. Infants were studied from the time of admission to the final end-point of transplantation, Norwood procedure, or death. Seventeen infants underwent BAS for clinical indications of oxygen saturation <80% in room air. Data collected included age at BAS, maximum velocity (V(max)), and IAC diameter throughout the clinical course. We assigned higher IAC scores to smaller IAC diameter, greater V(max) through the IAC, and lower oxygen saturation value. The minimum score was 3, and the maximum score was 9. Only 10% of infants with a score <6 at presentation required BAS, whereas 67% of those with scores > or =6 required BAS. Higher IAC scores at presentation were associated with earlier need for BAS (p = 0.04). The IAC scoring system can serve as a reliable clinical guide for identifying infants with hypoplastic left heart syndrome who are likely to require BAS for relief of critically restrictive IAC while awaiting cardiac transplantation.


All-arthroscopic versus mini-open repair of small to large sized rotator cuff tears: a meta-analysis of clinical outcomes.
The purpose of this study was to compare clinical outcomes of patients with full-thickness small to large sized tears undergoing all-arthroscopic versus mini-open rotator cuff repair. A literature search for electronic databases and references for eligible studies was conducted through Medline, Embase and Cochrane library between 1969 and 2013. A total of 12 comparative studies (n = 770 patients) were included. Pooled results showed: there were no differences in function outcome, pain scores, retear rate or the incidence of adhesive capsulitis between all arthroscopic and mini-open repair groups. There were no differences in outcomes between the arthroscopic and mini-open rotator cuff repair techniques, they should be considered alternative treatment options. Level IV, Meta analysis.


Management of the mucolabial fold when developing impressions for complete dentures.
All patients have loose nonkeratinized unattached mucosa in the anterior labial vestibule. The degree of possible distortion varies with each patient and with different recording techniques. Some distortion is possible in all patients. Common errors made when manipulating this tissue during impression procedures for complete dentures have been described. An effort to compensate for the errors in the finished denture will not correct them. Manipulation of the mucolabial fold must be done correctly during the border molding procedure. If not, the only recourse may be to reline the denture, and care should be taken not to repeat the errors.


Effects of histamine on coronary hemodynamics in humans: role of H1 and H2 receptors.
To evaluate whether histamine exerts a direct effect on coronary hemodynamics in humans, and to investigate the role played by H1 and H2 receptors in this response, intracoronary saline solution or histamine (4 micrograms) was administered in 10 patients with normal coronary arteries during diagnostic cardiac catheterization. Histamine injection was repeated after intravenous cimetidine (400 mg) and diphenhydramine (10 mg). The electrocardiogram, arterial pressure and thermodilution coronary blood flow were continuously monitored during and for 40 seconds after each injection. Immediately after histamine injection there was a significant increase in coronary blood flow (65 +/- 6%) and a decrease in coronary vascular resistance (-40 +/- 3%) (both p less than 0.001), with minor changes in the RR interval and the mean arterial pressure. H2 receptor blockade with cimetidine did not affect these changes, while H1 receptor blockade with diphenhydramine significantly reduced the histamine-induced increase in coronary blood flow and the decrease in coronary vascular resistance (26 +/- 6%, p less than 0.005 and -18 +/- 5%, p less than 0.001, respectively). Twenty to 30 seconds after histamine injection, a significant decrease in mean arterial pressure (-17 +/- 2%, p less than 0.001) and in the RR interval (-4 +/- 1%, p less than 0.01) was observed. These changes persisted after H2 receptor blockade with cimetidine, but were completely abolished after H1 receptor blockade with diphenhydramine. In each case coronary and systemic hemodynamics returned to normal within 40 seconds of the injection.(ABSTRACT TRUNCATED AT 250 WORDS)


Catalase positive particles from pig lung. Biochemical preparations and morphological studies.
In pig lung tissue catalase positive particles (CPs) are abundant especially in type II pneumocytes and in Clara cells. In both cell types they occur as circular, oval or elongated membrane profiles surrounding a moderately electron dense matrix lacking a crystalline core. In Clara cells and in part of type II pneumocytes they are located as individual particles without any evident morphological relation to other cell organelles. In part of type II pneumocytes 5-8 particles are forming a group and their close relation to agranular endoplasmic reticulum cisterns is evident. The particles can be purified from lung homogenates by fractionated pelleting and subsequent rate sedimentation in a sucrose gradient using a zonal rotor. The catalase rich fraction bands in the middle of the gradient whereas cytochrome oxidase and part of the acid phosphatase sediments at its heavy end. A second part of acid phosphatase stays at the light end of the gradient and--according to morphological control--seems to correspond to lamellar bodies of the type II pneumocytes. The purified catalase positive particles do not contain hydroxyacid and D-aminoacid oxidases thought to be characteristic H2O2 producing enzymes of peroxisomal systems. The buoyant density of the particles (d = 1.195 g/cm3) is lower than that of liver peroxisomes. Cytochemical controls of the peroxisomal pellets exhibit the particles partly uniformly filled with reaction product, partly irregularly stained.


Electrocardiographic diagnosis of left ventricular hypertrophy on the basis of dipole electrocardiotopography method.
The aim of this study was to verify a new criterion of hypertension-related left ventricular hypertrophy (LVH) on the basis of the dipole electrocardiotopographic technique, which provides intelligible pictorial patterns and efficient quantitative parameters for recognition of pathologic states of the heart. Standard 12-lead and vectorcardiographic measurements with the McFee-Parungao lead system were carried out for 289 echocardiographically accessed healthy subjects and hypertensive patients with LVH. The proposed parameter index of left ventricular hypertrophy for recognition of LVH is a product of the following 3 characteristics: maximum magnitude of depolarization vector, total duration of ventricular depolarization, and local spatial integral of activation duration. This parameter was compared with several other parameters commonly used for LVH diagnosis. The diagnostic efficiencies of these parameters were statistically estimated and compared using the receiver operating characteristics (ROC curves), area under the ROC curve, and partial areas under the ROC curve (pAUC). The area under the ROC curve values were compared by the standard nonparametric method, and pAUC comparison was performed by bootstrap methodology. The ROC curves display the definite advantage of the proposed criterion, especially for the specificities greater than 0.7. Statistical comparative analysis showed that the corresponding pAUC for the index of left ventricular hypertrophy is greater than for R(x) + S(z), Cornell product, and Sokolow-Lyon criteria at confidence level > or = .95. The dipole electrocardiotopography-based diagnostic criterion of LVH is demonstrated to be statistically more accurate as compared to other criteria studied. The advantage of this criterion suggests that with the use of decartograms, it is possible to reveal some additional information not accessible for other diagnostic tools. Decartograms help to visualize and quantify the redistribution of activation duration over the myocardium, thus providing a valuable instrument for heuristic analysis and dynamic observation of the heart state affected by LVH.


A SAS-macro for estimation of the cumulative incidence using Poisson regression.
In survival analyses, we often estimate the hazard rate of a specific cause. Sometimes the main focus is not the hazard rates but the cumulative incidences, i.e., the probability of having failed from a specific cause prior to a given time. The cumulative incidences may be calculated using the hazard rates, and the hazard rates are often estimated by the Cox regression. This procedure may not be suitable for large studies due to limited computer resources. Instead one uses Poisson regression, which approximates the Cox regression. Rosthøj et al. presented a SAS-macro for the estimation of the cumulative incidences based on the Cox regression. I present the functional form of the probabilities and variances when using piecewise constant hazard rates and a SAS-macro for the estimation using Poisson regression. The use of the macro is demonstrated through examples and compared to the macro presented by Rosthøj et al.


Fertility, root reserves and the cost of inducible defenses in the perennial plant Solanum carolinense.
We examined the relationship between internal resources (root reserves), external resources (soil fertility), and allocation to defense vs. growth in the clonal, perennial herb Solanum carolinense. In a short-term (9 d) greenhouse experiment, plants were treated once with jasmonic acid (JA) to determine if polyphenols and glycoalkaloids were inducible by simulated herbivory. In a longer-term (4 wk) greenhouse experiment, we measured the cost, in terms of growth, of treatment with JA every 3 d, to determine if the induced response was due more to carbon limitation or nitrogen limitation. We manipulated the resources available to the plants by varying soil fertility and the size of root cuttings from which plants were grown, and assessed how different resource levels affected the growth and production of polyphenols and alkaloids under JA treatment or control conditions. In the short term, JA increased the concentration of polyphenols in both above- and below-ground plant parts, as well as alkaloid concentrations in the roots. In the long term, the only significant secondary chemistry response to JA was an increased polyphenol concentration in above ground tissues. The total amount of polyphenols produced was the same for JA and control plants, indicating that the higher concentration was a result of the lower biomass of treated plants. In contrast, alkaloid concentrations in plants treated with JA for 4 wk did not differ from controls, but JA-treated plants contained lower total amounts of alkaloids in above ground tissues, as a result of decreased growth. Fertilizer level and root cutting size had effects on growth and the production of secondary compounds and influenced the cost of induction. Plants grown under high fertility had a greater reduction in growth in response to JA than plants grown under low fertility, indicating a greater trade-off between growth and defense for high fertility plants. Plants from larger root cuttings grew bigger without any reduction in the concentration of polyphenols and alkaloids. We demonstrated that the phenotype of S. carolinense was plastic in response to simulated herbivory, fertility level, and root cutting size, and that there was a significant growth cost to induction that varied with the environment and appears to be due in large part to the allocation of limited carbon reserves.


Normative treatment guidelines in home care: building the case.
To effectively market programs and maximize resources under a prospective payment system, home healthcare agencies need to look closely at standardizing treatment practices to link patient outcomes to the care provided. This article discusses the issues, methods, and processes used to test treatment guidelines and strategies to improve existing guidelines through evidence-based research.


[Central nervous system neuromodulation for the treatment of epilepsy].
We present here a review of the work on neuromodulation - defined as application of an inhibitory or excitatory current - on intracranial structures for the treatment of drug-resistant epilepsy. Near 250 patients were treated using a neuromodulation technique of the cerebellum (paravermian cortex), the CM-pf nucleus of the thalamus, the hippocampus, epileptogenic foci, and anterior ventral nucleus of the thalamus, with a one- to 15-year follow-up. Four contact strips were used for cerebellar and functional region neuromodulation, and DBS-type depth electrodes were stereotactically implanted for CM-pf and anterior nuclei of the thalamus and hippocampal neuromodulation. Electric stimulation was cyclic in almost all trials, using low frequency (10-40 Hz) for excitation and high frequency (60-185 Hz) for inhibition. Seizure frequency reduction was variable, depending on the neuromodulation site and patient selection, although seizure duration decreased in most patients. Cerebellar neuromodulation was followed by a 78% reduction in tonic and tonic-clonic seizures, CM-pf neuromodulation by an 83% reduction in tonic-clonic seizures and atypical absence of Lennox-Gastaut syndrome, with a 17.2% seizure-free and drug-free patient rate. Hippocampal neuromodulation was followed by a 73% reduction in partial complex seizures, with a 33% seizure-free patient rate. Anterior ventral nucleus of the thalamus was followed by a 63% reduction in tonic-clonic, tonic and atonic seizures. Several prognostic factors were identified in order to improve future results. There was no mortality and morbidity was limited to skin erosion at the neurostimulator site. Seizure reduction was associated with improved neuropsychological performance and better quality of life. Neuromodulation is safe and effective for the treatment of epileptic seizures of various origins. Several targets may be associated in a single patient, especially when bilateral hippocampal seizure foci are present.


Molecular dynamics of poly(L-lactide) biopolymer studied by wide-line solid-state 1H and 2H NMR spectroscopy.
The molecular dynamics of poly(L-lactide) (PLLA) biopolymer was characterized through analyses of 1H and 2H NMR line-shapes and spin-lattice relaxation times at different temperatures. At low temperatures (e.g. 90 K), the methyl group rotation is dominant leading to a significant reduction in the proton second moment. Fast methyl group reorientation occurs at ca. 130 K. In additional to the fast methyl group rotation, hydroxyl groups start to reorient as the temperature increases further, eventually leading to the breakdown of the segments of the biopolymer chains above its glass transition temperature Tg of 323 K. The analyses of the 2H NMR line-shapes indicate that both the methyl and hydroxyl reorientations can be described by the so-called cone model, in which the former has three equilibrium positions with theta(C-D) = 70.5 degrees and phi = 120 degrees while the latter one exhibits two equilibrium positions with theta(O-D) = 78 degrees and phi = 180 degrees .