Conservation investment for rare plants in urban environments.
Budgets for species conservation limit actions. Expending resources in areas of high human density is costly and generally considered less likely to succeed. Yet, coastal California contains both a large fraction of narrowly endemic at-risk plant species as well as the state's three largest metropolitan regions. Hence understanding the capacity to protect species along the highly urbanized coast is a conservation priority. We examine at-risk plant populations along California's coastline from San Diego to north of San Francisco to better understand whether there is a relationship between human population density and: i) performance of at-risk plant populations; and ii) conservation spending. Answering these questions can help focus appropriate strategic conservation investment. Rare plant performance was measured using the annualized growth rate estimate between census periods using the California Natural Diversity Database. Human density was estimated using Census Bureau statistics from the year 2000. We found strong evidence for a lack of a relationship between human population density and plant population performance in California's coastal counties. Analyzing US Endangered Species expenditure reports, we found large differences in expenditures among counties, with plants in San Diego County receiving much higher expenditures than other locations. We found a slight positive relationship between expenditures on behalf of endangered species and human density. Together these data support the argument that conservation efforts by protecting habitats within urban environments are not less likely to be successful than in rural areas. Expenditures on behalf of federally listed endangered and threatened plants do not appear to be related to proximity to human populations. Given the evidence of sufficient performance in urban environments, along with a high potential to leverage public support for nature in urban environments, expenditures in these areas appear to be an appropriate use of conservation funds.


Nasal CPAP in obstructive sleep apnea: mechanisms of action.
Sixteen patients with the obstructive sleep apnea syndrome (OSAS) were studied for 1-2 h while receiving continuous positive airway pressure (CPAP) delivered via a nasal mask. Obstructive apneas were obliterated in all. Eight patients had studies of genioglossal muscle activity (GG EMG) and one patient had computed tomograms (CT) of the upper airway while on nasal CPAP. The GG EMG studies showed two patterns: suppression and augmentation of GG EMG while on CPAP. The CT scan showed the airway to be narrowed while the patient was awake off CPAP. It returned to a normal caliber when CPAP was applied, despite sleep. These results are interpreted to suggest three potential mechanisms of action for nasal CPAP in OSAS: 1) reduced upper airway resistance due to prevention of sleep-induced collapse of the airway; 2) reduced upper airway resistance due to dilatation of the airway by nasal CPAP beyond its dimension in the awake state; and 3) possible stimulation of mechanoreceptors leading to an increase in airway tone while CPAP is applied.


Effect of Plum pox virus on chemical composition and fruit quality of plum.
The quality of fruit from PPV (Plum pox virus)-infected plum (Prunus domestica L.) trees was investigated during the last 3 weeks of ripening using healthy tree (T3), tree with short-term infection (T2), and tree with long-term infection (T1). The pomological variables (presence of necrosis on fruit, color of fruit, color of flesh, firmness, soluble solids content, and fruit weight) and composition of nutritive compounds (sugars and organic acids) and bioactive compounds (phenolics: anthocyanins, flavonols, and hydroxycinnamic acids) were evaluated. The results indicated that the PPV infection modified the ripening process (the most in T1) and the composition of nutritive and bioactive compounds in the healthy-looking part of the fruit. Long-term infected tree (T1) yielded fruit with the poorest pomological traits and with the most modified composition of nutritive and phenolic compounds. The short-term PPV infected tree also produced fruit with significantly altered phytochemicals composition, although the pomological traits had not changed significantly.


Is mid-head resection a durable conservative option in the presence of poor femoral bone quality and distorted anatomy?
High medium-term survivorship of hip resurfacing arthroplasty in young patients has led to its increased usage. To achieve high survival rates, selecting patients with appropriate proximal femoral morphology and bone quality is important. For patients with poor bone quality or abnormal morphology, the mid-head resection technique is an alternative, bone-conserving procedure but whether this technique results in acceptable complications and survival is unknown. We therefore assessed (1) implant survivorship of a mid-head resection device during short- and medium-term followup, (2) hip function, (3) adverse radiographic features emphasizing proximal stress shielding, and (4) complications. We retrospectively reviewed 164 patients (171 hips) who underwent reconstruction with the Birmingham Mid-Head Resection device (Smith and Nephew Orthopaedics Ltd, Warwick, UK) between 2003 and 2008. Patients were reviewed with hip outcome questionnaires, clinical examination, and radiographs. We report findings in 156 of these 171 hips with a minimum followup of 2 years (mean, 3.5 years, range, 2-7.5 years). They include three successive iterations based on the same design rationale. There were four revisions during this period, including two femoral failures, giving 3.5-year survivorships of 97.4% and 98.7% with revision or reoperation for any reason and femoral failure as the end points, respectively. No patient is currently awaiting revision. Average hip function was 98%, as assessed by Oxford hip score. Five of the 87 intermediate-iteration (V1) stems showed proximal femoral stress shielding, a phenomenon not observed in the other two iterations. Four patients had asymptomatic below-knee deep venous thrombosis and one had nonfatal pulmonary embolism, all of which resolved uneventfully. The mid-head resection technique can circumvent the need for a more invasive procedure such as standard THA in patients who would benefit from a conservative arthroplasty but do not possess good femoral head bone quality or morphology.


Spatial regulation of the spindle assembly checkpoint and anaphase-promoting complex in Aspergillus nidulans.
The spindle assembly checkpoint (SAC) plays a critical role in preventing mitotic errors by inhibiting anaphase until all kinetochores are correctly attached to spindle microtubules. In spite of the economic and medical importance of filamentous fungi, relatively little is known about the behavior of SAC proteins in these organisms. In our efforts to understand the role of γ-tubulin in cell cycle regulation, we have created functional fluorescent protein fusions of four SAC proteins in Aspergillus nidulans, the homologs of Mad2, Mps1, Bub1/BubR1 and Bub3. Time-lapse imaging reveals that SAC proteins are in distinct compartments of the cell until early mitosis when they co-localize at the spindle pole body. SAC activity is, thus, spatially regulated in A. nidulans. Likewise, Cdc20, an activator of the anaphase-promoting complex/cyclosome, is excluded from interphase nuclei, but enters nuclei at mitotic onset and accumulates to a higher level in mitotic nuclei than in the surrounding nucleoplasm before leaving in anaphase/telophase. The activity of this critical cell cycle regulatory complex is likely regulated by the location of Cdc20. Finally, the γ-tubulin mutation mipAD159 causes a nuclear-specific failure of nuclear localization of Mps1 and Bub1/R1 but not of Cdc20, Bub3 or Mad2.


Walnut protein hydrolysates ameliorate alcohol-induced cognitive impairment (AICI) by alleviating oxidative stress and inflammation in the brain and improving hippocampal synaptic plasticity in Sprague-Dawley rats.
Alcohol-induced cognitive impairment (AICI) has become a public health concern and thus effective intervention is urgently needed. The present study aims to assess the amelioration effect of walnut protein hydrolysate (WPH) in AICI rats and elucidate the associated mechanism. The Morris water maze task verified the significant amelioration effect of WPH against learning and memory deficits. Moreover, a reduction of oxidative stress and inflammation in brain tissues was observed and the significant enhancement of brain-derived neurotrophic factor (BDNF), postsynaptic density protein (PSD95) and cAMP-response element binding protein (p-CREB) expression (P < 0.05) indicated the rescue of damaged hippocampal synaptic plasticity. In addition, after WPH administration, disorders of ERK and caspase-3 signal pathways, abnormality in the release of the neurotransmitters acetylcholine (ACh) and gamma-aminobutyric acid (GABA), and histopathological impairment in the hippocampus of AICI rats were ameliorated in a dose-dependent manner. Overall, the amelioration of AICI by WPH might result from the alleviation of oxidative stress and inflammation in brain tissue and the improvement of hippocampal synaptic plasticity.


Lung or Heart-Lung Transplant in Pulmonary Arterial Hypertension: What Is the Impact of Systemic Sclerosis?
Little is known about recipient characteristics and outcomes of patients with pulmonary arterial hypertension undergoing lung transplant, particularly those with systemic sclerosis-associated disease. Here, we describe the characteristics and outcomes of patients with pulmonary arterial hypertension undergoing lung transplant, focusing on systemic sclerosis-associated disease. This retrospective study included pulmonary arterial hypertension patients undergoing lung or heart-lung transplant between July 1992 and August 2013 at a single center. We evaluated 51 patients with pulmonary arterial hypertension (37.3% males; mean age of 45.3 ± 11.9 y). Of 51 patients, 9 (17.6%) had systemic sclerosis-associated pulmonary arterial hypertension. Pulmonary arterial hypertension patients without systemic sclerosis-associated disease had higher mean pulmonary arterial pressure (P = .002), higher pulmonary vascular resistance (P = .008), and were more likely to have severe right ventricular systolic dysfunction (P = .006) than individuals with the disease. Mean hospital stay posttransplant was similar in the 2 groups (42.2 ± 43.3 vs 43.1 ± 19.4 d; P = .20). Higher pretransplant creatinine clearance (P = .0005), forced vital capacity (P = .01), and absence of vasopressor/inotrope use (P = .03) were associated with shorter hospital stay. Mortality for pulmonary arterial hypertension patients with versus without systemic sclerosis-associated disease was 0% versus 13% at 1 year, 29% versus 24% at 2 years, and 86% versus 53% at 5 years. Female sex (hazard ratio, 0.23; 95% confidence interval, 0.08-0.68) and less severe tricuspid regurgitation (hazard ratio, 0.31; 95% confidence interval, 0.11-0.89) were independently associated with long-term survival. Pulmonary arterial hypertension patients with versus without systemic sclerosis-associated disease have comparable short-term and 2-year outcomes after lung or heart-lung transplant. Female sex and less severe tricuspid regurgitation were independently associated with better long-term survival. These outcomes did not vary when adjusted for the year of transplant.


Superloading of tin ligands into rhodium and iridium carbonyl cluster complexes.
The reactions of Rh4(CO)12 and Ir4(CO)12 with Ph3SnH have yielded the new Rh-Sn and Ir-Sn cluster complexes M3(CO)6(mu-SnPh2)3(SnPh3)3, 1 (M=Rh) and 2 (M=Ir). Both compounds contain triangular M3 clusters with three bridging SnPh2 and three terminal SnPh3 ligands. The M-M bonds are unusually long. Molecular orbital calculations indicate that this is due to the importance of M-Sn bonding and weak direct M-M interactions. Reaction of 1 with Ph3SnH at reflux in 1,2-dichlorobenzene solvent yielded the complex Rh3(CO)3(SnPh3)3(mu-SnPh2)3(mu3-SnPh)2, 3, which contains eight tin ligands: three terminal SnPh3, three edge-bridging SnPh2, and two triply bridging SnPh ligands.


Effect of testosterone propionate on the ultrastructure of the preputial gland in the rat.
Testosterone propionate accelerates the maturation of acinar cells in the preputial gland of female rats. The weight of the preputial gland was increased significantly and the gland contained a large amount of secretory material. Various stages of maturation of acinar cells were observed. In an early stage, cells contained predominantly rough endoplasmic reticulum. In a second stage, lipid accumulated in association with focal areas of smooth endoplasmic reticulum. Membrane-bound dense bodies similar to lysosomes and secondary lysosomes predominated in a late stage. In the final stage, acini fused with a duct, thereby liberating the cells into the ductal lumen. Cell structure then became unrecognizable.


Transplantation of blood-derived progenitor cells after recanalization of chronic coronary artery occlusion: first randomized and placebo-controlled study.
Transplantation of blood-derived circulating progenitor cells (CPC) has been shown to improve myocardial regeneration after myocardial infarction. It remains unclear whether CPC transplantation exerts beneficial effects also in patients with chronic myocardial ischemia. We initiated a randomized, double-blind, placebo-controlled study evaluating the impact of intracoronary infusion of CPCs on coronary vasomotion and left ventricular (LV) function in patients after recanalization of chronic coronary total occlusion (CTO). After recanalization of CTO, 26 patients (age, 63+/-2 years; LV ejection fraction, 53+/-2%) were randomly assigned to the treatment (intracoronary transplantation of CPCs) or control group. Coronary flow reserve in response to adenosine (2.4 mg/min) was measured in the target vessel at the beginning of the study and after 3 months. LV function and infarct size were assessed by MRI and metabolism by 18F deoxyglucose positron emission tomography. CPC application resulted in an increase in coronary flow reserve by 43% from 2.3+/-0.3 to 3.3+/-0.5 (P<0.05 versus beginning and control). At 3 months, the number of hibernating segments in the target region (from 2.9+/-0.6 to 2.0+/-0.6 segments, P<0.05 versus beginning and control) had declined in the treatment group, whereas no significant changes were observed in the control group. MRI revealed a reduction in infarct size by 16% and an increase in LV ejection fraction by 14% in the treatment group (from 51.7+/-3.7 to 58.9+/-3.2%; P<0.05 versus beginning and control) because of an augmented wall motion in the target region. Hence, intracoronary transplantation of CPCs after recanalization of CTO results in an improvement of macro- and microvascular function and contributes to the recruitment of hibernating myocardium.


Green Propolis: Thirteen Constituents of Polar Extract and Total Flavonoids Evaluated During Six Years through RP-HPLC.
In order to verify the chemical qualities of polar extract of Green Propolis produced in the State of Minas Gerais, Brazil, was analyzed by means of RP-HPLC, the concentration of eleven flavonoids, Artepillin C and p-coumaric acid were analyzed by means of RP-HPLC. Samples were collected in the months of February, March, May, July, September, and October, during a period of six years (2008 to 2013) and the results compared with purchased standards. Artepillin C was the main constituent (80-90%) found in all samples. Lower concentrations of p-coumaric acid, chrysin and kaempferide were observed in March, and of ricin and galangin in September. Respectively, these months correspond to the end of Summer and Spring period in Brazil. The variation in concentration of the analyzed constituents always occurred in the same month, during the entire six years of evaluation period. All thirteen constituents of Green Propolis were detected throughout the study period, and the average concentration of each one was similar in relation to the respective monthly collection period of each year. Due to similarities among chemical constituents of Green Propolis with those present in B. dracuncufolia, this plant was identified as being the principal source of Green Propolis.


[The hand : review of the main pathologies for the primary care physician].
The general practitioner is often the first person to have to assess and treat a patient complaining about his hand, especially in areas far away from an emergency health center. The hand is the largest sensitive area of our cortex. It is the most used part of our body and is therefore prone to traumas, cuts, infections, tendinous inflammation and compressive nerve disorders. This article summarises the main pathologies a primary care physician has to deal with.


Total synthesis of (+)-stachyflin: a potential anti-influenza A virus agent.
The first enantioselective total synthesis of (+)-stachyflin, a potential anti-influenza A virus agent, was achieved; the method features a BF(3).Et(2)O-induced domino epoxide-opening/rearrangement/cyclization reaction to stereoselectively form the requisite pentacyclic ring system in one step.


Adult-onset hypophosphatemic osteomalacia associated with Sjogren syndrome: Clinical case report.
Hypophosphatemic osteomalacia (HO) is a metabolic bone disease, exhibiting different etiologies such as genetic mutation, tumor induction, dysimmunity, or renal disease. Sjogren's syndrome (SS) is a connective tissue disorder commonly involving exocrine glands; however kidney involvement is also encountered, leading to abnormal phosphorus metabolism, even HO. A 47-year-old female patient presented progressively worsening pain in the chest wall, back and bilateral lower extremities as well as muscle weakness was referred to our department. Due to the laboratory test results, radiographic findings and pathologic results, she was diagnosed with adult-onset HO associated with SS. She was then treated with alkalinization, steroids, neutral phosphate, calcium supplements together with activated vitamin D. So far, she recovered uneventfully with relieved pain and increased serum phosphorus level. HO may be secondary to renal tubular acidosis of SS patients, and it might be a diagnostic challenge when the kidney involvement in SS is latent and precede the typical sicca symptoms.


Genomic characterization of Streptococcus equi subspecies zooepidemicus from a 2021 outbreak in Indiana with increased sow mortality.
Streptococcus equi subspecies zooepidemicus (S. zooepidemicus) was reported to cause epizootic outbreaks in swine, resulting in significant economic losses in Asia in the 1970s and in North America in 2019. In February 2021, another outbreak due to S. zooepidemicus occurred in 2-year-old adult sows in a production system in Indiana. Whole-genome sequencing analysis of three outbreak isolates from Indiana revealed that all were genetically distant from the isolates of a strain that caused high mortality events in Ohio and Tennessee in 2019, as well as from the ATCC 35246 strain that caused outbreaks in China in the 1970s. The Indiana outbreak isolates were also distantly related to outbreak-unrelated swine isolate AZ-45470 from Arizona but closely related to an S. zooepidemicus equine isolate from Iowa. Comparative genomic analysis revealed that one genomic island, GI-13, was unique to the genome of a representative Indiana outbreak isolate, IN-6992. The genomic islands GI-1, GI-3, and GI-10 were also present in IN-6992 but absent from the Ohio and Tennessee outbreak isolates. In addition, the ATCC 35246-type szM gene and the Fic domain-containing protein gene (bifA) were absent from IN-6992, while present in all isolates from the Ohio and Tennessee outbreaks. Our findings have significant implications for understanding, monitoring, and developing control measures against diseases caused by S. zooepidemicus.IMPORTANCEThis study highlights a Streptococcus equi subspecies zooepidemicus (S. zooepidemicus) strain isolated from an outbreak in Indiana, which resulted in mortality events among a swine herd in 2021. The Indiana outbreak strain was found to be genetically and phylogenetically distant to a strain isolated from the 2019 outbreaks in Ohio and Tennessee, which caused high swine mortality. We also discovered multiple unique genetic features in the Indiana outbreak strain, including distinct S. zooepidemicus genomic islands, and notable S. zooepidemicus virulence genes-many of which could serve as biomarkers for the diagnosis of this strain. These findings provide significant insights into monitoring and potentially preventing severe outbreaks caused by the Indiana outbreak strain in the future.


The History of the Department of Cardiovascular and Thoracic Surgery at Rush.
The Rush Department of Cardiovascular and Thoracic Surgery received certification by the American Board of Thoracic Surgery (ABTS) to train thoracic surgical residents in 1962. The outstanding clinical faculty, with nationally recognized technical expertise, was eager to provide resident education. The hallmark of the program has been clinical excellence, dedication to patient care, and outstanding results in complex cardiac, vascular, and general thoracic surgical procedures. A strong commitment to resident education has been carried to the present time. Development of the sternotomy incision, thoracic and abdominal aneurysm repair, carotid endarterectomy, along with valve replacement, have been the hallmark of the section of cardiovascular surgery. Innovation in bronchoplastic lung resection, aggressive approach to thoracic malignancy, and segmental resection for lung cancer identify the section of general thoracic surgery. A total of 131 thoracic residents have been trained by the Rush Thoracic Surgery program, and many achieved their vascular certificate, as well. Their training has been vigorous and, at times, difficult. They carry the Rush thoracic surgical commitment of excellence in clinical surgery and patient care throughout the country, both in practice groups and academic centers.


Fat Necrosis Mimicking Local Recurrence With Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Positivity After Partial Nephrectomy for Renal Cell Carcinoma.
We report a case of fat necrosis with positive results on fluorodeoxyglucose positron emission tomography (FDG-PET)-CT imaging after partial nephrectomy. A 77-year-old man underwent a partial nephrectomy for a right renal mass. The histopathological results showed clear cell renal cell carcinoma, G1>G2, pT1a. Four and a half years after surgery, a nodule appeared in the retroperitoneal space on CT. FDG-PET CT showed increased uptake in the nodule, indicating local recurrence of carcinoma. A right nephrectomy was performed. The histopathological diagnosis was fat necrosis.


Investigation of the SH3BP2 gene mutation in cherubism.
Cherubism is a rare developmental lesion of the jaw that is generally inherited as an autosomal dominant trait. Recent studies have revealed point mutations in the SH3BP2 gene in cherubism patients. In this study, we examined a 6-year-old Korean boy and his family. We found a Pro418Arg mutation in the SH3BP2 gene of the patient and his mother. A father and his 30-month-old younger brother had no mutations. Immunohistochemically, the multinucleated giant cells proved positive for CD68 and tartrate-resistant acid phosphatase (TRAP). Numerous spindle-shaped stromal cells expressed a ligand for receptor activator of nuclear factor kB (RANKL), but not in multinucleated giant cells. These results provide evidence that RANKL plays a critical role in the differentiation of osteoclast precursor cells to multinucleated giant cells in cherubism. Additionally, genetic analysis may be a useful method for differentiation of cherubism.


[Comparative study between cardiac catheterization intervention therapy and transthoracic small incision surgery for closure of congenital atrial septal defect by domestic occluder with echocardiographic monitoring].
To evaluate the safety of cardiac catheterization intervention therapy and transthoracic small incision surgery in the occlusion bydomestic occluder under echocardiography guiding in patients with atrial septal defect (ASD). Methods: A total of 1 080 patients with ASD in the occlusion by domestic occluder were analyzed retrospectively, and the interventional treatment were performed in 734 cases through cardiac catheterization intervention therapy and 346 cases through transthoracic small incision surgery. The patients undergone cardiac catheterization intervention therapy were guided under the digital substraction angiography (DSA) and were monitored by transthoracic echocardiography (TTE) in the whole interventional process, and the efficacy was evaluated with TTE. The occlusion of transthoracic small incision surgery was guided under the transesophageal echocardiography (TEE), which was used to monitor the position of occluder and evaluate the efficacy immediately. Results: Two kinds of intervention in the occlusion by domestic occluder had achieved satisfactory results in patients with ASD. There was no statistically difference in the longest size of ASD between the 2 intervention methods, while there were statistically differences in the ratio between ASD longest diameter and atrial septal length, and the size of the occlusion, and the disparity between the size of the occluder and ASD longest diameter (D value), respectively (all P<0.05). When the size of arithmetic mean of the ASD was <30 mm, the success rate of the 2 methods was both 100%. When the size of arithmetic mean of the ASD was ≥30 mm, the success rate was 100% in the transthoracic small incision surgery and 50% in the cardiac catheterization intervention therapy. Conclusion: Domestic occluder is safe. Compared with the imported one, its cost is lower. When the size of the defects is same, the occlusion is smaller in the transthoracic small incision surgery compared with that in the cardiac catheterization intervention therapy. When the size of arithmetic mean of the ASD is ≥30 mm, the success rate of the transthoracic small incision surgery is higher compared with the cardiac catheterization intervention therapy. When the cardiac catheterization intervention therapy fails, the transthoracic small incision surgery may be a better choice.


Characterizing the microbiota of instrumentation in ophthalmology clinics during and beyond the COVID-19 pandemic.
Increased ophthalmology-specific risk of novel coronavirus 2019 (SARS-CoV-2) transmission is well-established, increasing the fear of infection and causing associated decreased rates of procedures known to save vision. However, the potential transmission from exposure to clinic instrumentation is unknown, including which additional pathogens may be spreading in this context. This study seeks to fill this gap by characterizing the microbiota of instrumentation in ophthalmology clinics during the COVID-19 pandemic and identifying potential sources of pathogenic spread encountered by patients and healthcare workers. Thirty-three samples were captured using standard cultures and media. Ten positive and negative controls were used to confirm proper technique. Descriptive statistics were calculated for all samples. Samples were collected from the retina (N = 17), glaucoma (N = 6), cornea (N = 6), and resident (N = 4) clinics with rigorous disinfection standards at a tertiary academic medical center. Standard media cultures and/or polymerase chain reaction (PCR) was performed for each sample. From 33 samples, more than half (17/33, 51.5%) yielded bacterial growth. Using two different molecular methods, three samples (3/33, 9%) tested positive for SARS-CoV-2 (cycle thresholds 36.48, 37.14, and 37.83). There was no significant difference in bacterial growth (95% confidence interval [95% CI]: - 0.644-0.358, p = 0.076) among different clinics (retina, glaucoma, cornea, resident). Staphylococcus (S.) epidermidis grew most frequently (12/35, 34%), followed by S. capitis (7/35, 20%), Micrococcus luteus (2/35, 5.7%), Corynebacterium tuberculostearicum (2/35, 5.7%), and Cutibacterium ([C.], Propionibacterium) acnes (2/35, 5.7%). C. acnes growth was more frequent with imaging device forehead rests (2/7, 28.6%) than other surfaces (0/26, 0%, 95% CI: 0.019-0.619, p = 0.040). No samples isolated fungus or adenovirus. Most samples across subspecialty clinic instrumentation grew bacteria, and several tested positive for SARS-CoV-2. Many isolated pathogens have been implicated in causing infections such as endophthalmitis, conjunctivitis, uveitis, and keratitis. The clinical implications of the ophthalmology microbiome for transmitting nosocomial infections warrant optimization of disinfection practices, strategies for mitigating spread, and additional study beyond the pandemic.


DFT and experimental exploration of intramolecular [2 + 2 + 2] cycloaddition of oxanorbornadienedicarboxylates and analogues.
The facile intramolecular [2 + 2 + 2] homo-Diels-Alder cycloadditions of oxanorbornadienedicarboxylates and analogues have been investigated by theoretical calculations using B3LYP and M06-2X density functional methods and experimental confirmation. The oxanorbornadienedicarboxylates formed from furans and but-2-ynedioates undergo the resulting intramolecular [2 + 2 + 2] cycloaddition in a concerted but asynchronous fashion, requiring energy barriers of about 30 kcal/mol to construct five- and three-membered rings simultaneously. Bridgehead substitutents have little influence on the regioselectivity, whereas 5-substitutents involving steric hindrance or electron-acceptor groups are predicted to attenuate the cycloaddition at the substituted side. Furthermore, the linker length, unsaturated bonds, and bridge-ring size are very sensitive to the cyclization rate. Additionally, aza- and norbornadienedicarboxylates demonstrate less reactivity, while thionorbornadienedicarboxylates show more reactivity with the challenge of their synthesis. The intermolecular version was also evaluated in comparison with the intramolecular version. Finally, our experimental tests verified the calculational prediction of the regioselectivity and reactivity.


Antibodies Capable of Enhancing SARS-CoV-2 Infection Can Circulate in Patients with Severe COVID-19.
Antibody-dependent enhancement (ADE) has been shown previously for SARS-CoV-1, MERS-CoV, and SARS-CoV-2 infection in vitro. In this study, the first monoclonal antibody (mAb) that causes ADE in a SARS-CoV-2 in vivo model was identified. mAb RS2 against the SARS-CoV-2 S-protein was developed using hybridoma technology. mAb RS2 demonstrated sub-nanomolar affinity and ability to neutralize SARS-CoV-2 infection in vitro with IC50 360 ng/mL. In an animal model of SARS-CoV-2 infection, the dose-dependent protective efficacy of mAb RS2 was revealed. However, in post-exposure prophylaxis, the administration of mAb RS2 led to an increase in the viral load in the respiratory tract of animals. Three groups of blood plasma were examined for antibodies competing with mAb RS2: (1) plasmas from vaccinated donors without COVID-19; (2) plasmas from volunteers with mild symptoms of COVID-19; (3) plasmas from patients with severe COVID-19. It was demonstrated that antibodies competing with mAb RS2 were significantly more often recorded in sera from volunteers with severe COVID-19. The results demonstrated for the first time that in animals, SARS-CoV-2 can induce antibody/antibodies that can elicit ADE. Moreover, in the sera of patients with severe COVID-19, there are antibodies competing for the binding of an epitope that is recognized by the ADE-eliciting mAb.


[Five-year analysis of microbial landscape of transplantation and dialysis center (20112015)].
Treatment of bacterial infections is pressing and difficult task of modern transplantology. To analyze the spectrum of bacterial microflora and bacterial sensitivity to antibiotics in patients of the transplantation and dialysis center. The study analyzed the results of bacteriological tests performed in 534 patients with chronic kidney disease stage 5 in 2011-2015. Biomaterials for the examination included urine, blood, wound discharge and sputum. Gram-positive bacteria, Gram-negative bacteria, fungi and mixed flora were found in 42%, 39%, 4% and 15%, respectively. Among observed associations 51% were presented by a combination of Gram-positive and Gram-negative bacteria and the others were different combinations of fungi. The most often detected bacteria were Enterococcus spp. (37%), Klebsiella pneumoniae (25%), Staphylococcus spp. (19%), E. coli (13%), Streptococcus spp. (6%), P. aeruginosa (5%). Fungi of the genus Candida were isolated from 11% of all cultures. Enterococci and Klebsiella had pronounced resistance to most antibiotics. All gram-positive bacteria were highly sensitive to vancomycin and linezolid. The findings suggest that the percentage of Gram-negative bacteria that are resistant to antibiotics is increasing. Significant changes in the microbial landscape and the growing antibiotic resistance dictate the need for periodic analysis of the bacterial flora in the transplantation and dialysis center.


Anemia is associated with cognitive impairment in adolescent girls: A cross-sectional survey.
Anemia is associated with impairment in oxygen transport, affecting an individual's physical and mental wellbeing, and work performance. The aim of this study was to examine the prevalence of anemia and its possible association with serum antibody titers to Hsp27 (as an indicator of cellular stress), cognitive function, measures of emotion, and sleep patterns in adolescent girls. A total of 940 adolescent girls were assessed to evaluate neuropsychological function with validated questionnaires. A complete blood count was determined as part of the assessment of hematological parameters. Serum anti-Hsp27 was measured for each subject. Among the total of 940 participants, 99 girls (10.5%) were anemic [hemoglobin <12(g/dL)]. Serum anti-HSP27 was significantly higher in anemic compared to healthy girls (p < 0.05). There was no significant differences in depression, aggression, insomnia, daytime sleepiness and sleep apnea score between two groups. However, the total cognitive abilities score was significantly lower in the anemic girls (76.8 ± 2.1 vs. 85.7 ± 2.5, p = 0.002). Logistic regression analysis showed that anemic girls were 1.73 times more likely than nonanemic girls to have cognitive impairment (95% confidence interval [CI] = 1.07-2.78; P = 0.025). Anemia was associated with elevated levels of anti-HSP27 and supports the hypothesis that cellular stress may be associated with anemia. Anemia was adversely associated with an assessment of cognitive abilities and was an independent risk factor for cognitive impairment in this group.


An 18-year comparison of hybrid total hip replacement and Birmingham hip resurfacing in active young patients.
To compare the long-term clinical and radiological results of metal-on-polyethylene hybrid total hip replacement (THA) with metal-on-metal Birmingham hip resurfacing (BHR) in young, active patients. From the 1st consecutive 63 hips in young, active patients who underwent BHR by the senior author, 54 (51 patients) were matched to patients who had undergone THA with regard to age, gender, body mass index and preoperative levels of activity. Radiologically, all hips were assessed for migration and osteolysis, THAs for polyethylene wear and BHRs for a pedestal sign. Patient-reported outcomes, mortality and revision rates were compared. The mean follow-up of the patients with a hybrid THR was 19.9 years and for those with a BHR, 17.6 years. 13 patients with a hybrid THR and 5 with a BHR had died. 1 hybrid THR and 3 BHRs were lost to follow-up. The revision rate of the hybrid THRs was 14/54 and of the BHRs 6/54. Log rank comparison of Kaplan-Meier survival estimates demonstrated a significantly lower mortality in the BHR group (p = 0.039; hazard ratio [HR] = 0.37 [95% CI, 0.15-0.95]) but a non-significant difference in revision rates (p = 0.067; HR = 0.43 [95% CI, 0.18-1.06]). The BHRs recorded superior OHS (p = 0.03), UCLA (p = 0.0096), and EuroQol visual analogue scores (p = 0.03). Significantly more BHRs had run, played sport and undertaken heavy manual labour in the month preceding follow-up. After 18 years, patients with BHRs remained more active with a lower mortality rate but demonstrated no significant difference in revision rates. Both groups demonstrated progressive radiological changes at long-term follow-up.


Spliceosome-mediated RNA trans-splicing.
RNA repair or reprogramming is a new avenue for human gene therapy. Unlike conventional gene therapy, in which exogenous cDNAs are introduced into cells, RNA repair approaches, which are based on spliceosome-mediated pre-mRNA trans-splicing, trans-splicing ribozymes, and tRNA-splicing endonuclease, allow the correction of endogenous RNA species. Recently published accounts that in vivo phenotypic correction of a variety of inherited diseases can be achieved by RNA repair are encouraging. Nevertheless, the science of RNA repair for treatment of human diseases is just beginning and faces several scientific and technical challenges that must be addressed and surmounted. In this review, we summarize recent advances in spliceosome-mediated pre-mRNA trans-splicing. We also provide an update on the progress of this emerging technology toward the development of molecular therapy and diagnosis for human diseases and discuss the outstanding issues and challenges confronting RNA therapeutics.


Thermal vaporization-vacuum ultraviolet laser ionization time-of-flight mass spectrometry of single aerosol particles.
Single aerosol particles of ethylene glycol and oleic acid are vaporized on a heater at temperatures between 500 and 700 K, and the resulting vapor plume is ionized by a 10.5-eV vacuum ultraviolet (VUV) laser. The mass spectra are compared to those obtained by CO2 laser vaporization followed by VUV laser ionization. The relative intensities of the parent and fragment ion peaks are remarkably similar for the two modes of vaporization. A Maxwell-Boltzmann distribution of speeds accurately describes the dependence of the signal as a function of the VUV laser pulse timing. The signal levels obtained with this design are sufficient to obtain good-quality mass spectra.


Abnormal Brain Activation During Theory of Mind Tasks in Schizophrenia: A Meta-Analysis.
Social cognition abilities are severely impaired in schizophrenia (SZ). The current meta-analysis used foci of 21 individual studies on functional abnormalities in the schizophrenic brain in order to identify regions that reveal convergent under- or over-activation during theory of mind (TOM) tasks. Studies were included in the analyses when contrasting tasks that require the processing of mental states with tasks which did not. Only studies that investigated patients with an ICD or DSM diagnosis were included. Quantitative voxel-based meta-analyses were done using Seed-based d Mapping software. Common TOM regions like medial-prefrontal cortex and temporo-parietal junction revealed abnormal activation in schizophrenic patients: Under-activation was identified in the medial prefrontal cortex, left orbito-frontal cortex, and in a small section of the left posterior temporo-parietal junction. Remarkably, robust over-activation was identified in a more dorsal, bilateral section of the temporo-parietal junction. Further abnormal activation was identified in medial occipito-parietal cortex, right premotor areas, left cingulate gyrus, and lingual gyrus. The findings of this study suggest that SZ patients simultaneously show over- and under-activation in TOM-related regions. Especially interesting, temporo-parietal junction reveals diverging activation patterns with an under-activating left posterior and an over-activating bilateral dorsal section. In conclusion, SZ patients show less specialized brain activation in regions linked to TOM and increased activation in attention-related networks suggesting compensatory effects.


Determinants of vascular permeability in the kidney glomerulus.
The human kidneys filter 70 liters of blood plasma every day. The hallmark of almost all kidney diseases, whether acquired or genetic, is the leakage of plasma proteins into the urine because of alterations in the glomerular filtration unit of the kidney. In this regard, the human mutations in nephrin, podocin, alpha-actinin-4, COL4A3, and COL4A5 genes expressed in the glomeruli have been implicated to cause alterations in glomerular filtration apparatus. Nevertheless, the expression of these proteins in relation to each other in mouse models for glomerular vascular leak is unknown. Additionally, within the glomerulus, the central question of whether the primary filtration barrier is the basement membrane or the epithelial slit diaphragm remains ambiguous. Therefore, in this study, we examined the localization and expression of glomerular epithelial slit diaphragm and glomerular basement membrane proteins implicated in glomerular vascular leak using mice deficient in either the alpha3 chain of type IV collagen, the major constituent of glomerular basement membrane, or LMX1B transcription factor, which regulates the expression of key glomerular type IV collagen genes COL4A3 and COL4A4 or nephrin, a glomerular epithelial slit diaphragm-associated protein. This study demonstrates that decreased expression of slit diaphragm protein, nephrin, correlates with a loss of glomerular filter integrity. Additionally, we demonstrate that defects induced by proteins of glomerular basement membrane lead to an insidious plasma protein leak, whereas the defects induced by proteins in the glomerular epithelial slit diaphragms lead to a precipitous plasma protein leak.


Spiroxys contorta (Nematoda: spirurida) in gastric granulomas of Apalone spinifera pallida (Reptilia: testudines).
Non-caseating granulomas containing larval spirurid nematodes (Spiroxys contorta) were observed in the gastric submucosa and muscularis externa of two pallid spiny softshells (Apalone spinifera pallida) from northcentral Texas (USA). In early granulomas, nematodes were not surrounded by a fibrous capsule but in older, mature granulomas, a fibrous capsule was present. Granulomas without nematodes also were present.


Assessing the Feasibility of Replacing Standard-Dose Bacillus Calmette-Guérin Immunotherapy with Other Intravesical Instillation Therapies in Bladder Cancer Patients: A Network Meta-Analysis.
Bacillus Calmette-Guérin (BCG) immunotherapy plays a key role in patients with bladder cancer. The shortage of intravesical BCG has motivated researchers to seek alternatives with equivalent efficacy If other alternative intravesical agents have equivalent efficacy compared to BCG, then it may be feasible to replace standard BCG with alternative options. We searched all relevant evidence in multiple sources and key data was extracted from included studies. Conventional and network meta-analysis were conducted so that pooled odds ratios (ORs) for the event of tumor recurrence and progression can be computed. The relative efficacy of different intravesical instillation procedures was computed by pooled odds ratios and their 95% confidence or creditable intervals. Besides, several key model assumptions were evaluated in our analysis. Three intravesical instillation procedures have the potential for preventing tumor recurrence: standard-dose BCG (BCG_SD), Epirubicin (EPI) and Mitomycin C (MMC) (ORs < 1). Patients with BCG SD also exhibited a decreased risk of tumor recurrence and progression compared to those with EPI. No significant difference in the risk of tumor recurrence or progression was detected between patients treated with BCG_ SD and those with low-dose BCG (BCG_LD). Results of SUCRA indicated that BCG_EPI, BCG_ MMC and BCG SD had higher rankings with respect to tumor recurrence and progression. BCG SD, EPI and MMC exhibited established efficacy for preventing tumor recurrence in postoperative BC patients. The efficacy of BCG may not be significantly reduced if standard dose was reduced to a lower level. However, there is no consensus suggesting that intravesical BCG with standard dose can be replaced by alternating or sequentially combined intravesical instillation therapies.


Gum hypertrophy - an unusual presenting feature in a case of precursor T-cell acute lymphoblastic leukemia.
Acute lymphoblastic leukemia/lymphoma, the malignant transformation of T-cell or B-cell precursors, is the most common diagnosis in pediatric oncology. Precursor T-cell acute lymphoblastic leukemia/lymphoma commonly affects adolescents, and is associated with mediastinal mass in over half of the cases, with early dissemination to bone marrow, gonads and the central nervous system. We present a rare case of precursor T-cell acute lymphoblastic leukemia/lymphoma with initial oral manifestation, presenting with the unusual features of gum hypertrophy and involvement of upper jaw and palate in a 10-year-old boy. This report discusses the clinical presentation, histopathologic and immunologic features, and diagnosis of this malignancy.


[Cardiac transplant and artificial heart. Historical data].
After mentioning the importance of implementing these techniques, frecuently used both in USA and Spain, he refers to his experience on 70 dogs since the end of the 50's in the last century. Not only does he refer to the heterotopic transplant, on the neck, undertaken to test the importance of the denervation, maintenance of the viability of the organ using hypothermia, and the anatomopathologic study of the inmunologic rejection, but also to the orthotopic transplant, this is the replacement of one heart by other, using extracorporeal circulation. He refers to the first transplant practiced by Hardy, on the 23rd of January 1964, in which he unsuccessfully used the heart of a chimpanzee and to the one performed by Barnard the 3rd of December 1967, with a survival span of 18 days. He mentions current techniques to preserve the replacement heart, using POPS, as well as the procedures to avoid the rejection and the clinical experience in Spain until now, including the obtained results. Thereafter, he makes a detailed description of the Liotta's artificial heart, the Jarvik 7 (Symbyon, CardioWest), which provided a survival period of 112 days. Also he refers to the Jarvik 2000, the model of DeBakey, the Novacor, the AbioCor, explaining the experience achieved with them, ending with the description with the model proposed by Schenk, in Cleveland, the MagScrew TAH.


Bis-cycloheptyl-fused bis(imino)pyridine-cobalt catalysts for PE wax formation: positive effects of fluoride substitution on catalytic performance and thermal stability.
The α,α'-bis(imino)-2,3:5,6-bis(pentamethylene)pyridyl-cobalt(ii) chlorides, [2,3:5,6-{C4H8C(N(2-R1-4-R3-6-R2C6H2))}2C5HN] CoCl2 (R1 = Me, R2 = R3 = CH(p-FPh)2Co1; R1 = Et, R2 = R3 = CH(p-FPh)2Co2; R1 = i-Pr, R2 = R3 = CH(p-FPh)2Co3; R1 = Cl, R2 = R3 = CH(p-FPh)2Co4; R1 = F, R2 = R3 = CH(p-FPh)2Co5; R1 = F, R2 = R3 = CHPh2Co5'', R1 = R2 = Me, R3 = CH(p-FPh)2Co6; R1 = R3 = Me, R2 = CH(p-FPh)2Co7), have been synthesized by a one-pot template reaction of α,α'-dioxo-2,3:5,6-bis(pentamethylene)pyridine, cobalt(ii) chloride and the respective aniline in n-butanol. By contrast, the mixed cobalt(ii) chloride/acetate complex, [2,3:5,6-{C4H8C(N(2-F-4,6-(CH(p-FPh)2)2C6H2))}2C5HN]CoCl(OAc) (Co5'), was isolated when the corresponding template reaction was carried out in acetic acid. Structural characterization of Co4, Co5 and Co5'' revealed distorted square pyramidal geometries while six-coordinate Co5', incorporating a chelating acetate ligand, exhibited a distorted octahedral geometry. On activation with either MAO or MMAO, 2-fluoride-4,6-bis{di(p-fluorophenyl)methyl}-substituted Co5 showed maximum catalytic activity for ethylene polymerization at a high operating temperature of 60 °C (up to 2.1 × 107 g (PE) mol-1 (Co) h-1), producing highly linear (Tms > 121 °C), low molecular weight polyethylene waxes (Mw range: 1.5-5.0 kg mol-1) with narrow dispersity (Mw/Mn range: 1.7-2.9). End-group analysis of the waxes reveals β-H elimination as the dominant chain transfer process.


Functional magnetic resonance imaging (fMRI) changes and saliva production associated with acupuncture at LI-2 acupuncture point: a randomized controlled study.
Clinical studies suggest that acupuncture can stimulate saliva production and reduce xerostomia (dry mouth). We were interested in exploring the neuronal substrates involved in such responses. In a randomized, sham acupuncture controlled, subject blinded trial, twenty healthy volunteers received true and sham acupuncture in random order. Cortical regions that were activated or deactivated during the interventions were evaluated by functional magnetic resonance imaging (fMRI). Saliva production was also measured. Unilateral manual acupuncture stimulation at LI-2, a point commonly used in clinical practice to treat xerostomia, was associated with bilateral activation of the insula and adjacent operculum. Sham acupuncture at an adjacent site induced neither activation nor deactivation. True acupuncture induced more saliva production than sham acupuncture. Acupuncture at LI-2 was associated with neuronal activations absent during sham acupuncture stimulation. Neuroimaging signal changes appear correlated to saliva production.


The potential for BACE1 inhibitors in the treatment of Alzheimer's disease.
Alzheimer's disease (AD) is a debilitating neurodegenerative disease of the elderly characterized by the loss of memory and other cognitive functions. Currently marketed drugs for the treatment of this disease only offer symptomatic relief, and, consequently, there is a large unmet clinical need for disease-modifying therapies for the treatment of AD. Substantial research efforts are focused on inhibiting the proteases involved in the generation of the amyloidogenic beta-amyloid (A beta) peptide. One of these key proteases, beta-secretase, was identified as a novel transmembrane aspartic protease and named BACE1. Due to its pivotal role in A beta production, many pharmaceutical companies are actively pursuing the challenging task of developing BACE1 inhibitors for evaluation in the clinic.


[Selecting the optimal treatment for depression taking into account the psychotropic and somatotropic effects of the antidepressant].
Based on a clinical case, the authors consider the problem of the optimal choice of an antidepressant, taking into account not only the psychopathological structure of depression, the severity and characteristics of its triad, but also the presence of somatic symptoms. This determines the need for a comprehensive analysis of the pharmacological profile of prescribed antidepressants, their psychotropic and somatotropic effects. The switch of the patient to brintellix, which has polymodal neuroreceptor activity, at a dose of 20 mg per day, made it possible to achieve remission and reduce adverse reactions caused by SSRIs.


Executive Resources and Item-Context Binding: Exploring the Influence of Concurrent Inhibition, Updating, and Shifting Tasks on Context Memory.
Previous research has demonstrated that context memory performance decreases as a result of cognitive load. However, the role of specific executive resources availability has not been specified yet. In a dual-task experiment, participants performed three kinds of concurrent task engaging: inhibition, updating, or shifting operations. In comparison with a no-load single-task condition, a significant decrease in item and context memory was observed, regardless of the kind of executive task. When executive load conditions were compared with non-specific cognitive load conditions, a significant interference effect was observed in the case of the inhibition task. The inhibition process appears to be an aspect of executive control, which relies on the same resource as item-context binding does, especially when binding refers to associations retrieved from long-term memory.


A new model for dura mater healing: human dural fibroblast culture.
Dura mater healing is crucial to prevent cerebrospinal fluid (CSF) leaks after neurosurgical procedures. Biological mechanisms leading to dural closure are only partially understood and have been studied in animals exclusively. We studied an in vitro model of dural closure which uses human cells. We used human dura intended for disposal after surgery. Explant primary cultures were performed. Cells were characterized through common staining and immunohistochemistry. A cell growth curve was elaborated and the effect of dexamethasone on cell count was assessed. Spongostan®, oxidized regenerated cellulose and autologous plastic materials were also evaluated for their effect on cellular growth. All specimens showed growth in fusiform cells, which project pseudopods and fuse into spindles. Cells showed desmin and vimentin positivity, and were negative for all the other stains, behaving phenotypically like fibroblasts. No collagen base was necessary for cell growth. Dexamethasone decreased cell count in the primary culture as well as in the explant, and reduced the cell proliferation marker Ki-67. Spongostan® was successfully used as a graft, and fibroblast cultures were additionally developed with muscle, pericranium, galea, and fascia. Oxidized cellulose induced cell death by lowering the pH of the solution. According to the findings, unlike mini-pigs and rabbits, in humans, dural fibroblast sensitivity to collagen seems to be lower. Dexamethasone inhibits fibroblast invasion, which is the biological base of wound dehiscence in cranial surgery. Although Spongostan is useful, Surgicel® can lower the media pH, thereby inhibiting cellular growth.


Data collection strategies for accessing adolescent women's worlds.
A two-year study was initiated in 1999 to investigate adolescent women's health concerns pertaining to their relationships. Data were obtained from four groups of girls (ages 14-19; N = 31) that met for approximately 18 weeks each. To help equalize power in the groups and facilitate a respectful and caring environment, we encouraged each group to use a variety of strategies, including those based on feminist principles. Data collection procedures based on feminist values can enable researchers to gain rich descriptions on the lived experience of adolescent women. Such procedures can help create an environment in which individuals can articulate their concerns and collectively co-construct the meanings of life events in health-promoting and consciousness-raising ways.


Ruxolitinib in addition to standard of care for the treatment of patients admitted to hospital with COVID-19 (RUXCOVID): a randomised, double-blind, placebo-controlled, phase 3 trial.
COVID-19 is associated with acute respiratory distress and cytokine release syndrome. The Janus kinase (JAK)1/JAK2 inhibitor ruxolitinib reduces inflammatory cytokine concentrations in disorders characterised by cytokine dysregulation, including graft-versus-host disease, myelofibrosis, and secondary hemophagocytic lymphohistiocytosis. We assessed whether treatment with the JAK1/JAK2 inhibitor ruxolitinib would be beneficial in patients with COVID-19 admitted to hospital. RUXCOVID was an international, randomised, double-blind, phase 3 trial of ruxolitinib plus standard of care versus placebo plus standard of care in patients with COVID-19. Patients who were hospitalised but not on mechanical ventilation or in the intensive care unit [ICU] were randomly assigned (2:1) to oral ruxolitinib 5 mg twice per day or placebo for 14 days (14 additional days were allowed if no improvement). The primary endpoint was a composite of death, respiratory failure (invasive ventilation), or ICU care by day 29, analysed by logistic regression including region, treatment, baseline clinical status, age, and sex as covariates. This trial is registered with ClinicalTrials.gov, NCT04362137. Between May 4 and Sept 19, 2020, 432 patients were randomly assigned to ruxolitinib (n=287) or placebo (n=145) plus standard of care; the mean age was 56·5 years (SD 13·3), 197 (46%) were female, and 235 (54%) were male. The primary objective was not met: the composite endpoint occurred in 34 (12%) of 284 ruxolitinib-treated patients versus 17 (12%) of 144 placebo-treated patients (odds ratio 0·91, 95% CI 0·48-1·73; p=0·77). By day 29, nine (3%) of 286 ruxolitinib-treated patients had died compared with three (2%) of 145 placebo-treated patients; 22 (8%) of 286 ruxolitinib-treated patients had received invasive ventilation compared with ten (7%) of 145 placebo-treated patients; and 30 (11%) of 284 ruxolitinib-treated patients had received ICU care compared with 17 (12%) of 144 placebo-treated patients. In an exploratory analysis, median time to recovery was 1 day faster with ruxolitinib versus placebo (8 days vs 9 days; hazard ratio 1·10, 95% CI 0·89-1·36). Adverse events included headache (23 [8%] of 281 on ruxolitinib vs 11 [8%] of 143 on placebo) and diarrhoea (21 [7%] vs 12 [8%]). Ruxolitinib 5 mg twice per day showed no benefit in the overall study population. A larger sample is required to determine the clinical importance of trends for increased efficacy in patient subgroups. Novartis and Incyte.


A highly unusual right atrial mass presented in two women.
Intravenous leiomyomatosis is a rare, benign neoplasm of the uterine, affecting adult women. We report two cases in whom intravenous leiomyomatosis extended through the inferior vena cava into the right heart chambers and the pulmonary artery. Both patients underwent staged operation with excision of the cardiac and primary tumour. The differential diagnosis of a right atrial mass in middle-aged women should include intravenous leiomyomatosis.


Whipple's disease. Report of a case with clinical immunological studies.
A case of Whipple's disease is described in which humoral and cellular immunity were tested. Histologic ultrastructural and immunocytochemical study were performed, before, during and after treatment. Cutaneous anergy was the main immunological dysfunction observed. During active Whipple's disease the patient had consistently negative skin tests for all antigens tested. This abnormality of delayed hypersensitivity regressed during treatment together with clinical remission of the disease. These findings are considered as secondary to Whipple's disease.


Basic polycations activate the insulin receptor kinase and a tightly associated serine kinase.
The effects of cationic polyamino acids on phosphorylation of the insulin and insulin-like growth factor 1 receptor kinases were studied and the following observations were made. (a) Polylysine stimulated both tyrosine and serine phosphorylation of the insulin receptor and of additional proteins present in lectin-purified membrane preparations from rat liver. (b) Polylysine synergized with insulin to enhance phosphorylation of the insulin receptor and of additional proteins (pp40 and pp110). (c) Polylysine effects were more pronounced upon increasing the polylysine chain length. (d) The effect of polylysine was biphasic with an optimum at 100 micrograms/ml. (e) Polylysine was found ineffective in stimulating the phosphorylation of immobilized insulin receptors. Taken together, these findings support the notion that the action of polylysine involves conformational changes and presumably aggregation of soluble receptors. The same effects of polylysine were obtained with highly purified insulin receptor preparations. Under these conditions polylysine enhanced both serine and tyrosine phosphorylation of the insulin receptor, suggesting that polylysine stimulates the activity of the insulin receptor kinase, and of a serine kinase that is tightly associated with the insulin receptor.


Temporal relationships critical to progesterone-induced acceleration of ovum transport.
Previous investigators have demonstrated that 2.5 mg fo progesterone, administered intramuscularly to rabbits on the day of ovulation and the 2 preceding days (Days -2, -1, and 0) significantly and consistently accelerates ovum transport. In contrast, when given on the day of ovulation and the 2 following days (Days 0, +1, and +2), progesterone does not accelerate ovum transport. The experiments reported were designed to define more precisely the temporal relationships critical to progesterone-induced acceleration of tubal ovum transport. Our observations suggest 3 important conclusions: 1) Progesterone, when given at least 1 day, and not more than 2 days, prior to ovulation does induce accelerated ovum transport. 2) The progesterone responsive mechanism is dose dependent. 3) The acceleration is partially antagonized if progesterone treatment is begun 3 days prior to ovulation.


Fabrication of low-cost thermo-optic variable wave plate based on waveguides patterned on di-ureasil hybrids.
An integrated variable wave plate device based on a thermo-optic (TO) effect was fabricated by patterning a waveguide channel through direct UV laser writing on the surface of sol-gel derived organic-inorganic hybrid (di-ureasil) films. The di-ureasil layer is stable up to 250 °C and has a high TO coefficient calculated as -(4.9 ± 0.5) × 10(-4) °C(-1) at 1550 nm. The waveguide temperature was tuned, inducing optical phase retardation between the transverse electric and transverse magnetic modes, resulting in a controllable wave plate. A maximum phase retardation of 77 ° was achieved for a waveguide induced temperature increase of 5 °C above room temperature, with a power consumption of 0.4 W. The thermal linear retardation coefficient was calculated to be 19 ± 1 °/ °C.


Identification of diarylsulfone sulfonamides as secreted frizzled related protein-1 (sFRP-1) inhibitors.
Inhibitor of secreted frizzled related protein-1 (sFRP-1) would be a novel potential osteogenic agent, since loss of sFRP-1 affects osteoblast proliferation, differentiation, and activity, resulting in improved bone mineral density, quality, and strength. We have identified small molecule diarylsulfone sulfonamide derivatives as sFRP-1 inhibitors. Structure-activity relationship generated for various regions of the scaffold was utilized to improve the biochemical profile, resulting in the identification of potent selective analogues, such as 16 with desirable pharmaceutical profile.


Acute rheumatic fever in Los Angeles County.
There was a general downward trend in the reported incidence of acute rheumatic fever in Los Angeles County during the years 1954-1963. A survey of hospital records in five large hospitals in 1962 revealed 100 cases diagnosed, 39 of which were reported. Diagnoses in the charts reviewed conformed to the Modified Jones Criteria. Most of the patients were born in Los Angeles County. Mortality rates for acute rheumatic fever during the same period were greatly in excess of those expected from the reported morbidity. The mean crude mortality rate for the period concerned was higher than for New York City, although not as high as for Boston.Acute rheumatic fever appears to constitute a health problem in need of review in Los Angeles County.


Multiple chemical sensitivity syndrome: a clinical perspective. II. Evaluation, diagnostic testing, treatment, and social considerations.
Multiple chemical sensitivity syndrome (MCS) does not appear to fit established principles of toxicology. Social, political, and economic forces are demanding that MCS be defined medically, even though scientific studies have failed as yet to identify pathogenic mechanisms for the condition or any objective diagnostic criteria. Consequently, a working definition of MCS can only rely on a person's subjective symptoms of distress and attribution to environmental exposures rather than currently measurable objective evidence of disease. Nevertheless, patients labeled with MCS are clearly distressed and many are functionally disabled. Without reconciling the different theories of etiology of MCS discussed in Part I of this report, and recognizing that the cause of the syndrome may be multifactorial, strategies are proposed for clinical evaluation and management of patients with MCS using a biopsychosocial model of illness. The social implications of this illness are also discussed.


Efficacy of a single dose of mebendazole on prevalence and intensity of soil-transmitted nematodes in Zanzibar.
The efficacy of a single-dose of mebendazole to treat intestinal helminths was studied in Pemba Island, Zanzibar, with the view of incorporating it in future control programmes. A single Kato-Katz stool examination was performed on 2,269 individuals from all age groups. 1,883 individuals were treated with 500 mg of mebendazole (250 mg for children below two years) and re-examined one month and four months after therapy. A total of 466 presented themselves for all three surveys and the data has been reported in this study. The overall cure rate for ascariasis was 93.2% and reduction of egg load after treatment was 89.8% in persistent positive cases. Although the cure rates were lower in trichuriasis (25.6%) and hookworm (17.8%) infections, egg reduction was more evident with 47% for Trichuris trichiura and 51.9% for hookworms. A single dose of mebendazole results not only in a high cure rate for ascariasis but also in a decrease in intensity of ascariasis, trichuriasis and hookworm infections, thereby contributing to its incorporation into low-budget control programmes in developing countries.


Crystal structure of yeast nitronate monooxygenase from Cyberlindnera saturnus.
Nitronate monooxygenase (NMO) is an FMN-dependent enzyme that oxidizes the neurotoxin propionate 3-nitronate (P3N) and represents the best-known system for P3N detoxification in different organisms. The crystal structure of the first eukaryotic Class I NMO from Cyberlindnera saturnus (CsNMO) has been solved at 1.65 Å resolution and refined to an R-factor of 14.0%. The three-dimensional structures of yeast CsNMO and bacterial PaNMO are highly conserved with the exception of three additional loops on the surface in the CsNMO enzyme and differences in four active sites residues. A PEG molecule was identified in the structure and formed extensive interactions with CsNMO, suggesting a specific binding site; however, 8% PEG showed no significant effect on the enzyme activity. This new crystal structure of a eukaryotic NMO provides insight into the function of this class of enzymes.


Improved synthesis of (3E,7Z)-3,7-tetradecadienyl acetate, the major sex pheromone constituent of the potato pest Symmetrischema tangolias (Gyen).
An efficient six-step synthesis of (3E,7Z)-3,7-tetradecadienyl acetate, the major component of the sex pheromone of the potato pest Symmetrischema tangolias (Gyen), is described, starting from the commercially available dihydropyran. The stereoselective formation of the 7Z double bond is accomplished by a Wittig reaction, while the 3E double bond is formed by a modified Knoevenagel condensation. The overall yield of the synthesis is 28%, giving the final product in high stereochemical purity (95%). The simplicity and the low cost of the herein reported synthesis suggest the potential practical use of the above pheromone in integrated management programs, for this serious insect pest.


Stress, anxiety, and cognitive interference: reactions to tests.
The nature of test anxiety and its relationships to performance and cognitive interference are analyzed from the standpoint of attentional processes. A new instrument to assess dimensions of reactions to tests is presented, and its psychometric properties are described. The scales of the Reactions to Tests questionnaire (Worry, Tension, Test-Irrelevant Thinking, Bodily Symptoms) were compared with regard to intellective performance and cognitive interference. The results were consistent with the idea that the problem of anxiety is, to a significant extent, a problem of intrusive thoughts that interfere with task-focused thinking. In the last of the three studies reported, it was shown that self- preoccupying intrusive thinking can be reduced by means of a task-focusing experimental condition. The studies suggest that the Reactions to Tests questionnaire may be useful in defining anxiety more sharply and improving understanding of how it relates to performance.


[Effects of climate change on Public Health 2015-2020. A systematic review.]
Anthropogenic climate change is a phenomenon that is becoming increasingly important in many areas such as economics and politics, but it also has great scientific relevance due to the important effects it has on people's health, the relationship between climate change and Health has caused an increase in the production of scientific knowledge about this topic and therefore the objective of this article was to provide an updated review of the open access scientific evidence, in the last five years, related to the effects of anthropogenic climate change in Public Health. A systematic review was conducted, in Spanish and English, in four non-subscription databases; using online thesaurus terms, the inclusion and exclusion criteria, an evaluation with the STROBE checklist were applied. Finally, 18 publications were analyzed. These showed: the relationship between extreme events, such as heat and cold waves, with the increase in mortality from various causes, especially from heart attacks; the alteration of the rainy and drought periods as a determinant of various infectious diseases; air pollution from emissions derived from the use of fossil fuels with the reduction of 2.9 years in world life expectancy. In addition, other authors reported predictions from climate alterations in health risks; and perceptions of the population, and decision-makers about the impacts of climate change on Public Health. The studies, regardless of the region or country, showing the relationships and impacts, local and global, of climatic variations on the health of populations.


Carcinoid tumors of the appendix. Our experience in a university hospital.
To present our experience of carcinoid tumors of the appendix managed at a university teaching hospital. Complex symptomatology, varied biochemical affections and different surgical therapeutic modalities are discussed. The medical records of all the patients who underwent consecutive appendectomies at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia from 1994 to 1999 were retrospectively analyzed. The data of patients identified to have histological evidence of carcinoid tumors of the appendix were further reviewed for the demographic details, indications for surgery, surgical procedure, tumor localization in the appendix and size; concomitant appendicitis and further surgical procedures were considered. During the study period, 1547 appendectomies were performed and, out of these, 9 (0.6%) cases were reported to have carcinoid tumors of the appendix. There were 4 male and 5 female patients, age range 17-51 years (median 29.8 years). Seven subjects had a clinical evidence of appendicitis while 2 presented with chronic abdominal pain. There were 6 open and 3 laparoscopic appendectomies. Six carcinoid tumors were encountered at the appendiceal apex, 2 at the midportion, and one at the base with a mean diameter of 9.5 mm (range, 4-19 mm). One patient had histologically confirmed residual tumor, which necessitated a right hemicolectomy 3 weeks later. All patients remained disease-free during a mean follow up of 7 years (range, 4-10 years). Carcinoid tumors of the appendix are extremely rare and invariably remain asymptomatic. Simple appendectomy offers adequate relief while the need for further extensive surgery depends on tumor characteristics and dissemination. Despite an excellent prognosis, all reported patients should be followed up with urinary 5-hydroxyindoleacetic acid and abdominal ultrasonography.


Shear alignment and realignment of sphere-forming and cylinder-forming block-copolymer thin films.
In common with many other structured fluids, block copolymers can be effectively oriented by shear. This susceptibility to shear alignment has previously been shown to hold even in thin films, containing as few as two layers of spherical microdomains, or even a single layer of cylindrical microdomains. A phenomenological model has been proposed [M. W. Wu, R. A. Register, and P. M. Chaikin, Phys. Rev. E 74, 040801(R) (2006)] to describe the alignment of such block-copolymer films, yielding the microdomain lattice order parameter as a function of shearing temperature, stress, and time. Here we directly test the central idea of that model, that the grains which are most misaligned with the shear direction are selectively destroyed, to reform in a direction more closely aligned with the shear. Films are first shear aligned from a polygrain state into a monodomain orientation and are then subjected to a second shear, at a variable stress (sigma) and misorientation angle (deltatheta) relative to the monodomain director, allowing the effects of sigma and deltatheta to be independently and systematically probed. For both cylinder-forming and sphere-forming block copolymers, these experiments confirm the basic premise of the model, as the stress required for realignment increases monotonically as deltatheta becomes smaller. For a cylinder-forming block copolymer, we find that the characteristic stress sigma(c) required to realign cylinders from one monodomain orientation to another is indistinguishable from that required to generate a monodomain orientation from the polygrain state. By contrast, the hexagonal lattice of spheres requires a value of sigma(c) more than 3 times as high for reorientation than for generation of the initial monodomain orientation.


Alterations of red blood cell proteolysis in favism.
Damaged RBC drawn from favic patients during acute hemolysis showed marked alterations in their two major proteolytic systems. Cytosolic procalpain (i.e., the proenzyme species of Ca2+-activated neutral proteinase, or calpain) had considerably lower activity than in matched RBC from asymptomatic G6PD-deficient subjects. The total RBC activity of the three acid endopeptidases that are normally membrane-bound was not reduced in favism, but its subcellular distribution was mostly cytosolic, suggesting quantitative release from membranes. Changes in procalpain activity are the result of both autoxidation of divicine and of the intracellular elevation of Ca2+ that is found in favism. Changes in acid endopeptidase activity are the consequence of perturbed Ca2+ homeostasis. Overall, the picture shows a marked impairment of the RBC proteolytic machinery that in turn may worsen cellular damage.


Current treatment of lacrimal gland carcinoma.
The traditional treatment for lacrimal gland carcinoma is orbital exenteration followed by radiation therapy. However, orbital exenteration does not prevent distant relapse and death, and some patients experience local-regional recurrence after exenteration. More recently, eye-sparing surgery and adjuvant radiation therapy and chemotherapy have gained popularity in the treatment of lacrimal gland carcinoma. Preliminary studies show that these approaches are associated with reasonable local control rates and ocular toxicity profiles. In this review, we discuss recent studies of treatment of lacrimal gland carcinoma, including studies of potential molecular treatment targets. Recent studies suggest promising results for neoadjuvant intra-arterial chemotherapy followed by orbital exenteration and adjuvant intravenous chemotherapy, but only in patients with an 'intact lacrimal artery'. Recent studies of globe-sparing surgery followed by adjuvant proton radiation therapy or concurrent chemoradiation suggest good local control, reasonable rates of eye preservation, and low risk of serious ocular toxic effects. Larger tumor size and predominant basaloid histology seem to be associated with higher risk of local-regional recurrence and distant metastasis. One study showed oncogenic mutations in more than half of cases of lacrimal gland adenoid cystic carcinoma, with KRAS mutations in 10 of 24 patients, suggesting potential benefit of treatments targeting the EGFR-RAS-RAF cascade. In selected patients with lacrimal gland carcinoma, eye-sparing surgery with eye-sparing radiation therapy offers preservation of visual function with good local control and minimal radiation-induced ocular toxic effects. In patients with recurrent or metastatic disease, a search for actionable cancer-associated mutations may be prudent.


Irreversible ototoxicity associated with difluoromethylornithine.
Difluoromethylornithine (DFMO) is a potent, irreversible inhibitor of ornithine decarboxylase, the rate-limiting enzyme in the synthesis of polyamines that promote cellular proliferation. DFMO has been tested as a potential cancer therapeutic and chemopreventive agent in clinical trials. Reversible hearing loss is a recognized toxicity of DFMO that usually occurs at doses above 2 g/m(2)/d, and generally when the cumulative dose exceeds 250 g/m(2). In a recently completed Barrett's esophagus chemoprevention trial, a participant developed a 15-dB decrease in hearing at frequencies of 250, 2,000, and 3,000 Hz in the right ear and a > or =20-dB decrease in hearing at 4,000 to 6,000 Hz in the left ear after taking 0.5 g/m(2)/d DFMO for approximately 13 weeks (cumulative dose of 45 g/m(2)). The threshold shifts persisted 7 months after DFMO was discontinued. There was no obvious impact on the participant's clinical hearing, but these findings were consistent with irreversible hearing loss. This is the first case reported of irreversible ototoxicity in a clinical trial participant receiving DFMO and, thus, trial participants should be made aware of this small but important risk.


13-Year-Old Female With New Onset Multifocal Pulmonary Ground-Glass Opacities.
A 13-year-old female who recently emigrated from Honduras presented to an emergency department in Texas with a 2-month history of weight loss, fatigue, cough, and progressive shortness of breath. Her symptoms started with a nonproductive cough, and she later developed dyspnea on exertion and orthopnea. On physical examination, she was tachycardic and tachypneic. She had a thin, emaciated body habitus. She was visibly in respiratory distress with nasal flaring, tracheal tugging, and intercostal and subcostal retractions. She had diminished breath sounds at the bases and bibasilar crackles. A computed tomography scan of the chest revealed multifocal ground-glass opacities throughout all lobes of both lungs with small bilateral pleural effusions and prominent bilateral hilar lymph nodes. We will discuss the approach to the initial evaluation and subsequent diagnosis.


Population Pharmacokinetic Analyses for Plazomicin Using Pooled Data from Phase 1, 2, and 3 Clinical Studies.
Plazomicin is an aminoglycoside with activity against multidrug-resistant Enterobacteriaceae Plazomicin is dosed on a milligram-per-kilogram-of-body-weight basis and administered by a 30-min intravenous infusion every 24 h, with dose adjustments being made for renal impairment and a body weight (BW) of ≥125% of ideal BW. A population pharmacokinetic analysis was performed to identify patient factors that account for variability in pharmacokinetics and to determine if dose adjustments are warranted based on covariates. The analysis included 143 healthy adults and 421 adults with complicated urinary tract infection (cUTI), acute pyelonephritis, bloodstream infection, or hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia (HABP/VABP) from seven studies (phases 1 to 3). A three-compartment structural pharmacokinetic model with a zero-order rate constant for the intravenous infusion and linear first-order elimination kinetics best described the plasma concentration-time profiles. The base structural model included creatinine clearance (CLCR) as a time-varying covariate for clearance. The covariates included age, BW, height, body surface area, body mass index, sex, race, and disease-related factors. The ranges of the α-, β-, and γ-phase half-lives for the analysis population were 0.328 to 1.58, 2.77 to 5.38, and 25.8 to 36.5 h, respectively. Total and renal clearances in a typical cUTI or HABP/VABP patient were 4.57 and 4.08 liters/h, respectively. Starting dose adjustments for CLCR are sufficient for minimizing the variation in plasma exposure across patient populations; adjustments based on other covariates are not warranted. The results support initial dosing on a milligram-per-kilogram basis with adjustments for CLCR and BW. Subsequent adjustments based on therapeutic drug management are recommended in certain subsets of patients, including the critically ill and renally impaired.


Residual infestation and recolonization during urban Triatoma infestans Bug Control Campaign, Peru.
Chagas disease vector control campaigns are being conducted in Latin America, but little is known about medium-term or long-term effectiveness of these efforts, especially in urban areas. After analyzing entomologic data for 56,491 households during the treatment phase of a Triatoma infestans bug control campaign in Arequipa, Peru, during 2003-2011, we estimated that 97.1% of residual infestations are attributable to untreated households. Multivariate models for the surveillance phase of the campaign obtained during 2009-2012 confirm that nonparticipation in the initial treatment phase is a major risk factor (odds ratio [OR] 21.5, 95% CI 3.35-138). Infestation during surveillance also increased over time (OR 1.55, 95% CI 1.15-2.09 per year). In addition, we observed a negative interaction between nonparticipation and time (OR 0.73, 95% CI 0.53-0.99), suggesting that recolonization by vectors progressively dilutes risk associated with nonparticipation. Although the treatment phase was effective, recolonization in untreated households threatens the long-term success of vector control.


[Status of the microcirculatory bed of the bulbar conjunctiva in various forms of vestibular dysfunction].
Using biomicroscopy of the eye conjunctiva, blood microcirculation was investigated in 200 patients with vestibular dysfunction (cervical osteochondrosis, Ménière's disease, neurocirculatory dystonia). All the patients showed microcirculation changes such as arteriolar spasms, reduced number of functioning capillaries, congestion and convolution of venules of medium and small caliber, and red blood cell aggregation. Capillary blood flow was intermittent: dash-dotted or bead-like. The arteriovenular coefficient decreased. Blood microcirculation changes were detected on the normal and affected sides of patients with cervical osteochondrosis, mostly on the affected side of patients with Ménière's disease, and on both sides of patients with neurocirculatory dystonia. Short-term changes in blood flow of vertebral arteries caused by head movements led to reflex responses of blood microcirculation of the conjunctiva. These reactions were most distinct in patients with cervical osteochondrosis and Mérière's disease. Eye conjunctiva biomicroscopy carried out during provocative tests with head movements may be used as a diagnostic test for identifying the type of vascular changes (vasoparetic or vasospastic) in vestibular dysfunction.


Effects of fluid and dobutamine treatment on renal function during partial superior mesenteric artery occlusion and reperfusion.
We compared the effects of dobutamine, fluid resuscitation and their combination on renal function during experimental intestinal ischaemia and reperfusion. Superior mesenteric artery (SMA) blood flow was reduced to 30% from the baseline for 120 minutes in 24 anaesthetized pigs (ischaemic group); 24 pigs (sham group) served as non-ischaemic controls. The animals were further assigned into four treatment arms. In the control arms, the animals were given only basic fluid therapy. In the fluid therapy arms, pulmonary capillary wedge pressure (PCWP) was maintained at 10 mmHg with intravenous fluids. In the dobutamine treatment arm, dobutamine hydrochloride was infused at a dose of 10 microg/min/kg. In the combined dobutamine-fluid therapy arms, dobutamine at 10 microg/min/kg was given and PCWP was maintained at 10 mmHg with fluids. At 120 minutes, the occluder was released in all study groups and the animals were followed for an additional 60 minutes. Renal function was evaluated by means of serum and urine creatinine. urine volume and creatinine clearance. Systemic and regional haemodynamics as well as intramucosal pH, intramucosal-arterial pCO2 gradient, and portal venous-arterial lactate gradient were measured. In the ischaemic groups, diuresis increased and serum and urine creatinine decreased significantly in fluid (p < 0.01, p < 0.01 and p < 0.05, respectively) and dobutamine-fluid (p < 0.01, p < 0.001 and p < 0.001, respectively) treated groups during SMA ischaemia. After SMA reperfusion, diuresis decreased in control group (p < 0.05) and in animals treated with dobutamine alone (p < 0.01). In addition, urine creatinine increased in dobutamine treated group (p < 0.05), and creatinine clearance decreased in control group (p < 0.01). Renal function and diuresis during the SMA occlusion and reperfusion did not differ between ischaemic and sham groups. All fluid treated groups had lower serum creatinine during SMA occlusion than control groups (p < 0.001). Intestinal ischaemia caused by partial SMA occlusion did not influence renal function. On the contrary, SMA reperfusion resulted in a significant impairment of renal function both in ischaemic and sham operated animals. The impairment was most obvious in control groups and in animals treated with dobutamine alone.


Mutated barley (1,3)-beta-D-glucan endohydrolases synthesize crystalline (1,3)-beta-D-glucans.
Barley (1,3)-beta-D-glucan endohydrolases (EC ), inactivated by site-directed mutagenesis of their catalytic nucleophiles, show autocondensation glucosynthetic activity with alpha-laminaribiosyl fluoride and heterocondensation glycosynthetic activity with alpha-laminaribiosyl fluoride and 4'-nitrophenyl beta-D-glucopyranoside. The native enzyme is a retaining endohydrolase of the family 17 group and catalyzes glycosyl transfer reactions at high substrate concentrations. Catalytic efficiencies (k(cat) K(m)(-1)) of mutants E231G, E231S, and E231A as glycosynthases are 28.9, 0.9, and 0.5 x 10(-4) m(-1) s(-1), respectively. Glycosynthase reactions appear to be processive and proceed with pH optima of 6-8 and yields of up to 75%. Insoluble products formed during the glycosynthase reaction appear as lamellar, hexagonal crystals when observed by electron microscopy. Methylation, NMR, and matrix-assisted laser desorption ionization time-of-flight analyses show that the reaction products are linear (1,3)-beta-D-glucans with a degree of polymerization of 30-34, whereas electron and x-ray diffraction patterns indicate that these (1,3)-beta-D-glucan chains adopt a parallel, triple helical conformation. The (1,3)-beta-D-glucan triple helices are orientated perpendicularly to the plane of the lamellar crystals. The barley (1,3)-beta-D-glucan glycosynthases have considerable potential for tailored and high efficiency synthesis of (1,3)-beta-D-linked oligo- and polysaccharides, some of which could have immunomodulating activity, or for the coupling of (1,3)-beta-D-linked glucosyl residues onto other oligosaccharides or glycoproteins.


In vitro synthesis of antimycobacterial antibodies with different specificities in various tissues of leprosy patients.
For the detection of the synthesis in vitro of anti-Mycobacterium leprae antibodies in various tissues of leprosy patients, biopsy specimens of skin lesions, nasal mucosa, larynx, lymph nodes, and bone marrow were cultured in a medium containing 14C-labeled lysine and isoleucine. The culture fluids were analyzed by crossed immunoelectrophoresis with intermediate gel and autoradiography. The results show that synthesis of anti-M. leprae antibodies occurs at the investigated sites of leprosy patients and that the specificities of the synthesized antibodies differ between sites in individual patients. It is conceivable that these antibodies play a role in the local defense against M. leprae.


Attitudes of Washington State physicians toward health care reform.
Attitudes of Washington State physicians about health care reform and about specific elements of managed competition and single-payer proposals were evaluated. Opinions about President Clinton's reform plan were also assessed. Washington physicians (n = 1,000) were surveyed from October to November 1993, and responses were collected through January 1994; responses were anonymous. The response rate was 80%. Practice characteristics of respondents did not differ from other physicians in the state. Of physicians responding, 80% favored substantial change in the current system, 43% favored managed competition, and 40% preferred a single-payer system. Of physicians responding, 64% thought President Clinton's proposal would not adequately address current problems. Reduced administrative burden, a central element of single-payer plans, was identified by 89% of respondents as likely to improve the current system. Other elements of reform plans enjoyed less support. More procedure-oriented specialists than primary care physicians favored leaving the current system unchanged (28% versus 8%, P < .001). While physicians favor health care reform, there is no consensus on any single plan. It seems unlikely that physicians will be able to speak with a single voice during the current debates on health care reform.


Compositional studies on succinoglycan-like extracellular water-soluble Rhizobium polysaccharides.
This study reports structural information on extracellular, water-soluble polysaccharides from 5 different strains of Rhizobium, viz. R. trifolii J60, R. meliloti J1017, 202, 204 and 207. All the 5 polysaccharides had glucose and galactose in approximate molar ratio of 7:1. Methylation analysis revealed that the polysaccharides contained (1 leads to 3), (1 leads to 6), (1 leads to 4), (1 leads to 4, 1 leads to 6)-linked D-glucose residues, (1 leads to 3)-linked D-galactose and non-reducing terminal D-glucose attached to pyruvate. This structure was found to be exactly the same as that of succinoglycan, a succinic acid containing water-soluble polysaccharide elaborated by Alcaligenes faecalis var. myxogenes 10C3. The similarity of the structure of polysaccharides of two different Rhizobium species and also to the polysaccharide produced by Alcaligenes are discussed in terms of host specificity.


Temporal requirement of Hoxa2 in cranial neural crest skeletal morphogenesis.
Little is known about the spatiotemporal requirement of Hox gene patterning activity in vertebrates. In Hoxa2 mouse mutants, the hyoid skeleton is replaced by a duplicated set of mandibular and middle ear structures. Here, we show that Hoxa2 is selectively required in cranial neural crest cells (NCCs). Moreover, we used a Cre-ERT2 recombinase system to induce a temporally controlled Hoxa2 deletion in the mouse. Hoxa2 inactivation after cranial NCC migration into branchial arches resulted in homeotic transformation of hyoid into mandibular arch skeletal derivatives, reproducing the conventional Hoxa2 knockout phenotype, and induced rapid changes in Alx4, Bapx1, Six2 and Msx1 expression patterns. Thus, hyoid NCCs retain a remarkable degree of plasticity even after their migration in the arch, and require Hoxa2 as an integral component of their morphogenetic program. Moreover, subpopulations of postmigratory NCCs required Hoxa2 at discrete time points to pattern distinct derivatives. This study provides the first temporal inactivation of a vertebrate Hox gene and illustrates Hox requirement during late morphogenetic processes.


Genetic evidence that cellulose synthase activity influences microtubule cortical array organization.
To identify factors that influence cytoskeletal organization we screened for Arabidopsis (Arabidopsis thaliana) mutants that show hypersensitivity to the microtubule destabilizing drug oryzalin. We cloned the genes corresponding to two of the 131 mutant lines obtained. The genes encoded mutant alleles of PROCUSTE1 and KORRIGAN, which both encode proteins that have previously been implicated in cellulose synthesis. Analysis of microtubules in the mutants revealed that both mutants have altered orientation of root cortical microtubules. Similarly, isoxaben, an inhibitor of cellulose synthesis, also altered the orientation of cortical microtubules while exogenous cellulose degradation did not. Thus, our results substantiate that proteins involved in cell wall biosynthesis influence cytoskeletal organization and indicate that this influence on cortical microtubule stability and orientation is correlated with cellulose synthesis rather than the integrity of the cell wall.


The Antimicrobial Effect of Melissa officinalis L. Essential Oil on Vibrio parahaemolyticus: Insights Based on the Cell Membrane and External Structure.
The study was to evaluate the antimicrobial impacts on Melissa officinalis L. essential oil (MOEO) against Vibrio parahaemolyticus. The minimum inhibitory concentration (MIC) of MOEO on Vibrio parahaemolyticus was 1 μL⋅mL-1. The kill-time curve exhibited that MOEO had good antimicrobial activity. The analysis of cellular ingredients leakage and cell viability illustrated that MOEO has destruction to the morphology of the cell membrane. The damage to the membrane integrity by MOEO has been confirmed by transmission and scanning electron microscopy, obvious morphological and ultrastructural changes were observed in the treated bacterial cells. The MOEO at 0.5 μL⋅mL-1 can inhibit the biofilm formation, biofilm motility, and extracellular polysaccharide production. Meanwhile, the qPCR results exhibited MOEO inhibited the expression of virulence genes. The findings showed that MOEO exerted its antimicrobial effect mainly by destroying the membrane, which indicated its potential as a natural food preservative.


The Effect of Modification on the Properties of Polyetherimide and Its Carbon-Filled Composite.
The effect of oligophenylene sulfone (OPSU) and polycarbonate (PC) on the rheological, mechanical and thermal properties of polyetherimide (PEI) and a carbon-filled composite based on it was studied. It is shown that the introduction of OPSU and PC leads to a decrease in the melt viscosity of PEI and a carbon-filled composite based on it with the preservation of their mechanical properties and heat resistance at a sufficiently high level. It was found that composites with OPSU have higher mechanical and thermal properties compared with composites with PC. Samples from modified carbon-filled PEI were printed by the fused deposit modeling (FDM) method. Three-dimensionally printed samples from carbon-filled PEI modified by OPSU showed significantly higher mechanical properties than composites with PC.


Groundnut Bud Necrosis Virus Modulates the Expression of Innate Immune, Endocytosis, and Cuticle Development-Associated Genes to Circulate and Propagate in Its Vector, Thrips palmi.
Thrips palmi (Thysanoptera: Thripidae) is the predominant tospovirus vector in Asia-Pacific region. It transmits economically damaging groundnut bud necrosis virus (GBNV, family Tospoviridae) in a persistent propagative manner. Thrips serve as the alternate host, and virus reservoirs making tospovirus management very challenging. Insecticides and host plant resistance remain ineffective in managing thrips-tospoviruses. Recent genomic approaches have led to understanding the molecular interactions of thrips-tospoviruses and identifying novel genetic targets. However, most of the studies are limited to Frankliniella species and tomato spotted wilt virus (TSWV). Amidst the limited information available on T. palmi-tospovirus relationships, the present study is the first report of the transcriptome-wide response of T. palmi associated with GBNV infection. The differential expression analyses of the triplicate transcriptome of viruliferous vs. nonviruliferous adult T. palmi identified a total of 2,363 (1,383 upregulated and 980 downregulated) significant transcripts. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed the abundance of differentially expressed genes (DEGs) involved in innate immune response, endocytosis, cuticle development, and receptor binding and signaling that mediate the virus invasion and multiplication in the vector system. Also, the gene regulatory network (GRN) of most significant DEGs showed the genes like ABC transporter, cytochrome P450, endocuticle structural glycoprotein, gamma-aminobutyric acid (GABA) receptor, heat shock protein 70, larval and pupal cuticle proteins, nephrin, proline-rich protein, sperm-associated antigen, UHRF1-binding protein, serpin, tyrosine-protein kinase receptor, etc., were enriched with higher degrees of interactions. Further, the expression of the candidate genes in response to GBNV infection was validated in reverse transcriptase-quantitative real-time PCR (RT-qPCR). This study leads to an understanding of molecular interactions between T. palmi and GBNV and suggests potential genetic targets for generic pest control.