The influence of seasonal temperature variation on embryonic development in two species of spider crabs (Majoidea).
The aim of this study was to analyze the ecological influence of seasonal temperature variations on embryonic development in two species of Majoidea. Leurocyclus tuberculosus and Libinia spinosa. These species inhabit stable populations in the San José Gulf (42°25'41″S, 64°08'27″O, Patagonia-Argentina) in a wide depth range and seasonal temperature variations from 8 °C to 18 °C. The influence of seasonal temperatures on embryonic development was examined in ovigerous females of both species, through a bioassay in laboratory conditions at 8 °C, 14 °C, and 18 °C from gastrula to hatching. Additionally, monthly female samplings were conducted for one year, characterizing their spatial depth distribution associated with the seawater temperature in the study area and their ovigerous/non ovigerous condition. Laboratory experimental results showed that duration of incubation increased 67 % in L. tuberculosus and 55% in L. spinosa by a decline in temperature from 18 °C to 8 °C with one diapause period. The embryonic development for the 3 assayed temperatures was divided in five periods. The assayed temperatures did not affect the morphology of the embryo, and its growth during each period did not present significant differences among the different temperatures. Field analysis showed significant differences in the spatial distribution of ovigerous females which were associated to the assessed temperatures along the year. This distribution might modulate the development of embryos leading to two spawnings synchronized with the phyto- and zooplankton peaks in the San José gulf. Finally, ecological and potential impact of ocean warming in these species was also addressed.


The impact of practice environment on laparoscopic colectomy utilization following colorectal residency: a survey of the ASCRS Young Surgeons.
It is often thought that practice patterns are different in private (PP) vs university hospital (UH) settings. We aimed to describe the impact of practice environment on the type of laparoscopic colectomy procedures performed by graduating colorectal surgeons. A review was carried out of prospectively gathered self-reported questionnaire data. Graduates of American Society of Colon and Rectal Surgeons' (ASCRS)-approved colorectal residencies from 2004 to 2008 underwent an on-line survey, developed by the ASCRS Young Surgeons' Committee. About 177 (52%) of 342 graduates surveyed responded. Practice setting data were available for 157 (89%) surgeons. Gender, geographical location and age were similar in both cohorts. PP surgeons utilized a laparoscopic approach more often for rectal cancer (37% vs 19%; P=0.003). There was no significant difference in the rate of laparoscopic surgery in colon cancer, diverticular disease, inflammatory bowel disease, Clostridium difficile or emergency surgery. PP surgeons operated more often with a partner (43% vs 8%) or surgical assistant (13% vs 4%; both P<0.001), while UH surgeons had a colorectal resident (10% vs 21%) or general surgery resident (15% vs 55%; both P<0.001). Impediments to performing laparoscopic surgery for PP surgeons included a perceived lack of hospital equipment (33% vs 20%) and support (29% vs 17%; both P<0.05). Perception of personal experience, access to trained assistants, financial reimbursement, length of surgery and patient availability were equivalent in both groups. While differences such as type of assistant and impediments to laparoscopic utilization exist between PP- and UH-based practices, early laparoscopic practice patterns remain similar. PP surgeons more frequently perform laparoscopic resection for rectal cancer and with hand-assistance. Despite differences, newly trained colorectal surgeons in both settings utilize and require laparoscopic skills.


A comparison of humoral responses to Schistosoma haematobium in areas with low and high levels of infection.
Antibody responses to Schistosoma haematobium of 280 Zimbabweans were studied in two areas of differing infection levels. 133 of the subjects came from a low infection area with a prevalence of 33.8% and geometric mean infection intensity of 0.8 eggs per 10ml of urine, while 147 of the subjects came from a high infection area with a prevalence of 62.7% and geometric mean intensity of 3.2 eggs per 10 ml of urine. Both the age-prevalence and age-intensity curves exhibited a peak shift. IgA, IgE, IgG, IgG1, IgG2, IgG3, IgG4, and IgM antibody levels against soluble egg antigen (SEA) and whole worm homogenate (WWH) were assayed by ELISA. Females produced significantly more anti-SEA IgG1, IgG4, IgM, anti-WWH IgE and IgG1. People from the high infection area produced significantly more anti-SEA IgE, IgG3 and anti-WWH IgG3 and significantly lower levels of anti-SEA IgA, IgM and anti-WWH IgM when the effects of infection intensity, sex and age had been allowed for. The age profiles of anti-SEA IgA, IgG and anti-WWH IgA and IgM reflected current levels of infection while anti-WWH IgG1, IgG2 and anti-SEA IgG1 evolved more slowly with age, and anti-WWH IgE rose with age in both areas. Some antibody responses, anti-SEA/WWH IgM, anti-SEA IgG1 and possibly anti-SEA/ WWH IgA showed different age profiles in the two areas, with changes in antibody levels occurring at a younger age in the high infection area suggesting that immune responses are evolving more rapidly in residents of this area. This result clearly demonstrates that antibody levels are not a function of age alone.


Thiolated and S-protected hydrophobically modified cross-linked poly(acrylic acid)--a new generation of multifunctional polymers.
The aim of this study was to create a novel multifunctional polymer by covalent attachment of l-cysteine to the polymeric backbone of hydrophobically modified cross-linked poly(acrylic acid) (AC1030). Secondly, the free thiol groups of the resulting thiomer were activated using 2-mercaptonicotinic acid (2-MNA) to provide full reactivity and stability. Within this study, 1167.36 μmol cysteine and 865.72 μmol 2-MNA could be coupled per gram polymer. Studies evaluating mucoadhesive properties revealed a 4-fold extended adherence time to native small intestinal mucosa for the thiomer (AC1030-cysteine) as well as an 18-fold prolonged adhesion for the preactivated thiomer (AC1030-Cyst-2-MNA) compared to the unmodified polymer. Modification of the polymer led to a higher tablet stability concerning the thiomer and the S-protected thiomer, but a decelerated water uptake could be observed only for the preactivated thiomer. Neither the novel conjugates nor the unmodified polymer showed severe toxicity on Caco-2 cells. Evaluation of emulsification capacity proofed the ability to incorporate lipophilic compounds like medium chain triglycerides and the preservation of the emulsifying properties after the modifications. According to these results thiolated AC1030 as well as the S-protected thiolated polymer might provide a promising tool for solid and semisolid formulations in pharmaceutical development.


Complete chloroplast genome of Toona sinensis (Meliaceae), a goluptious 'tree vegetables'.
Toona sinensis, also known as Xiangchun in Chinese, is a popular 'tree vegetables' and famous medicinal plant with good economic value. In our study, we sequenced the complete chloroplast (cp) genome of T. sinensis using the llumina sequencing platform. The cp genome of T. sinensis is a characteristic four-party structure with a length of 157,228 bp, which contains two 26,994 bp inverted repeats (IRs), an 85,971 bp large single copy (LSC), and a 17,269 bp small single copy (SSC). We identified a total of 126 genes, of which clouding 82 protein-coding genes, 36 tRNA genes, and eight rRNA genes. The phylogenetic analysis showed that T. sinensis was closely related to the congeneric T. ciliata.


Antimycin A increases bronchopulmonary C-fiber excitability via protein kinase C alpha.
Inflammation can increase the excitability of bronchopulmonary C-fibers leading to excessive sensations and reflexes (e.g. wheeze and cough). We have previously shown modulation of peripheral nerve terminal mitochondria by antimycin A causes hyperexcitability in TRPV1-expressing bronchopulmonary C-fibers through the activation of protein kinase C (PKC). Here, we have investigated the PKC isoform responsible for this signaling. We found PKCβ1, PKCδ and PKCε were expressed by many vagal neurons, with PKCα and PKCβ2 expressed by subsets of vagal neurons. In dissociated vagal neurons, antimycin A caused translocation of PKCα but not the other isoforms, and only in TRPV1-lineage neurons. In bronchopulmonary C-fiber recordings, antimycin A increased the number of action potentials evoked by α,β-methylene ATP. Selective inhibition of PKCα, PKCβ1 and PKCβ2 with 50 nM bisindolylmaleimide I prevented the antimycin-induced bronchopulmonary C-fiber hyperexcitability, whereas selective inhibition of only PKCβ1 and PKCβ2 with 50 nM LY333531 had no effect. We therefore conclude that PKCα is required for antimycin-induced increases in bronchopulmonary C-fiber excitability.


Relations of dissolved-oxygen variability, selected field constituents, and metabolism estimates to land use and nutrients in high-gradient Boston Mountain streams, Arkansas.
Continuous monitoring data can be extremely useful for assessing water-quality conditions particularly for variables, such as dissolved oxygen, that exhibit dynamic diel swings. As a means of evaluating stream dissolved oxygen criteria used by the Arkansas Department of Environmental Quality (ADEQ), we compared continuous dissolved oxygen (DO) data collected at five small- to moderate-sized (watersheds 10-100 mi2), high-gradient streams in the Boston Mountains distributed across a land-use and nutrient condition gradient. The sampled streams exhibit a general pattern established for other aquatic systems (e.g., larger streams, low-gradient streams, and lakes) where increasing land-use intensity results in increased nutrient concentrations, stream eutrophication, and increased DO variability. DO concentrations were < 6 mg/L for fewer than 4% of measurements at the two sites identified "a priori" as least disturbed by nutrient and land-use indices, while concentrations at the three sites identified as moderately and most disturbed were < 6 mg/L for 20 to 33% of measurements. These findings demonstrate that the current criterion (10% of the DO measurements are < 6 mg/L) employed by ADEQ was effective at identifying various degrees of DO impairment in Boston Mountain streams. Our analysis also demonstrated that continuous pH and specific conductance data and estimates of stream metabolism were helpful for attributing DO variability to anthropogenic or natural origins. Considerations that were useful for examining these relationships and evaluating ADEQ's DO criterion should be applicable to DO studies in other locations where stream and geologic characteristics are similar to those of the Boston Mountains.


Endoscopic removal of entirely embedded esophagus-penetrating foreign bodies (with video).
Traditionally, surgery is the only choice for esophageal foreign bodies (FBs) penetrating into the mediastinum or cervical para-esophageal space. Recent progress in endoscopic techniques and devices has made it possible to perform endoscopic procedures in the mediastinum. Here, we describe a novel method to remove the entirely embedded esophagus-penetrating FBs through an endoscopic approach. Patients who underwent endoscopic removal of entirely embedded esophagus-penetrating FBs were prospectively enrolled between December 2018 and June 2020. All procedures were performed by using five major steps: localization of the FB; mucosal incision; wound debridement, myotomy, and FB exposure; FB extraction; and closure of the esophageal wound. A total of five cases of entirely embedded esophagus-penetrating FBs were evaluated, two in children and three in adults. All FBs were successfully removed and extracted using a therapeutic endoscope and a hook knife or a hybrid knife and a grasping forceps as accessories. The average procedure time was 19.0 ± 12.4 min (range 10-40 min). The major surgical procedure was avoided in all patients. The average length of hospital stay was 3.8 ± 2.5 days (range 2-8 days). There were no severe short-term adverse events after all procedures. During the 1 month and 3 months follow-up, no patient developed long-term adverse events including stenosis of the esophagus and fistula formation. Endoscopic approach was a safe and effective way to remove entirely embedded esophagus-penetrating FBs.


Upregulation of erythropoietin in rat peripheral nervous system with experimental autoimmune neuritis.
The glycoprotein erythropoietin (EPO) is a multifunctional cytokine involved in erythropoiesis. Recent data have suggested that EPO and EPO receptors are expressed in the central nervous system, where EPO exerts neuroprotective effects. However, peripheral nervous system (PNS) EPO and EPO receptor expression has not been widely studied. EPO and EPO receptor expression was examined in the PNS in an experimental autoimmune neuritis (EAN) rat model in the present study to elucidate EPO/EPO-receptor binding pathway involvement in injured PNS tissue. Western blot analysis demonstrated that EPO was significantly increased in the PNS at the paralytic stage on day 14 post-immunization (PI); levels were significantly decreased at day 30 PI. EPO was identified in PNS-derived vascular endothelial cells, Schwann cells, and axons in normal control rats. Most inflammatory cells in EAN lesions were EPO immunopositive at day 14 PI. In addition, the intensity of EPO immunoreactivity in both Schwann and vascular endothelial cells was greater than that of normal controls at this stage; intensity declined at day 30 PI. These findings suggest that EPO is transiently upregulated in EAN lesions and that the EPO/EPO-receptor binding pathway is associated with neuroprotection in EAN-affected PNS tissues.


The influence of the adsorption of metoclopramide on the surface ionization of fumed silica.
The effect of adsorbed metoclopramide on the surface ionization of fumed silica was studied using potentiometric titration. Adsorption isotherms of metoclopramide to unionized and negatively-charged silica surfaces were generated and compared to the titration data. The adsorption of metoclopramide caused the silica surface charge to become more negative with increasing pH that was independent of ionic strength which suggested that specific adsorbate-surface interactions were occurring. Adsorption studies showed that metoclopramide adsorbs to the unionized silica surface. Ionization caused drug adsorption to increase which was consistent with at least two distinct surface adsorption sites. The ratio of the additional amount of metoclopramide adsorbed to the surface ionized group density determined from the titration curves was approximately unity which showed conclusively that the negatively-charged silanols constitute one of the surface adsorption sites. Potentiometric titration has been shown to be a useful technique for determining the number and types of adsorption sites on the silica surface.


Isolation and expression of a cDNA for human brain fatty acid-binding protein (B-FABP).
We have isolated and sequenced a novel 754-bp human fetal brain cDNA encoding a fatty acid-binding protein (FABP). The cDNA contains an open reading frame of 396 nucleotides (132 amino acids). Northern analysis revealed small amounts of a 1.2-kb transcript in adult human brain and a shorter transcript in skeletal muscle, but no message was detected in other tissues examined. On the other hand, it was abundantly expressed in fetal brain but not in fetal lung, liver or kidney tissues. The elevated level of transcript at immature stages and its subsequent decline In adult brain indicate that the encoded protein may be essential for development of the human brain.


Critical period exists in the effects of isolation rearing on sensorimotor gating function but not locomotor activity in rat.
Isolation-reared (IR) rats exhibit various cognitive and behavioral abnormalities in adulthood of which locomotor hyperactivity and impaired prepulse inhibition (PPI) of an acoustic startle reflex are the two cardinal characteristics. Using an amended social deprivation-resocialization paradigm, the present study examined the role of the developmental specificity of the effects of IR and its interaction with the non-competitive NMDA receptor antagonist, MK-801. Locomotor activity and PPI were measured in three groups of adult rats: social control, IR throughout life, and IR for the first two weeks after weaning followed by social housing. MK-801 was injected intraperitoneally (i.p.) 30 min prior to testing at doses of 0, 0.02, 0.1, and 0.2 mg/kg. The results revealed that locomotor activity increased only in rats in the IR throughout life group but not in the other two groups. The impairment of PPI was seen in rats in the IR for the first two weeks and the IR throughout life groups. Furthermore, the effect of MK-801 on PPI was bidirectional in rats of the IR for the first two weeks and IR throughout life groups but not in the social control group. These results suggest that the IR-induced behavioral effects are developed distinctively in terms of the critical period hypothesis, which strengthens the developmental hypothesis of schizophrenic-like dysfunctions.


Acoustic projectors make covert bioacoustic chirplet signals discoverable.
To disguise man-made communications as natural signals, underwater transceivers have the option to pre-record animal vocalizations, and play them back in a way that carries meaningful information for a trained receiver. This operation, known as biomimicking, has been used to perform covert communications and to emit broadband signals for localization, either by playing pre-recorded animal sounds back into the environment, or by designing artificial waveforms whose spectrum is close to that of bioacoustic sounds.However, organic sound-emitting body structures in animals have very different trans-characteristics with respect to electro-acoustic transducers used in underwater acoustic transceivers. In this paper, we observe the distortion induced by transmitting pre-recorded animal vocalization through a transducer's front-end, and argue that such distortion can be detected via appropriate entropy metrics. We test ten different metrics for this purpose, both via emulated transmission and in two field experiments. Our result indicate which signals and entropy metrics lead to the highest probability of detecting transducer-originated distortions, thus exposing ongoing covert communications. Our research emphasizes the limitations that man-made equipment incurs when reproducing bioacoustic sounds, and prompts for the choice of biomimicking signals that are possibly suboptimal for communications or localization, but help avoid exposing disguised transmissions.


[Sarcoidosis : Dermatological view of a rare multisystem disease].
Sarcoidosis is a rare multisystem inflammatory disease of largely unknown etiology. While pulmonary sarcoidosis is the most abundant organ manifestation, involvement of the skin that occurs in up to 30% of patients is the most common extrapulmonary presentation of the disease. Dermatologists therefore play an important role not only for establishing the diagnosis and delineating it from potential differential diagnoses but also for the interdisciplinary care of the patient. The clinical presentation of skin sarcoidosis is manifold, which occasionally aggravates making the final diagnosis. Specific skin lesions (with granulomas) and nonspecific skin manifestations (without granulomas) can be differentiated. Since a variety of organ systems can be affected, multidisciplinary cooperation is mandatory. Therapy of sarcoidosis is difficult; evidence-based studies and therapy guidelines are widely lacking. Our review intends to outline the characteristic clinical presentations of cutaneous sarcoidosis, describe the diagnostic approach and how to assure or exclude extracutaneous manifestations of sarcoidosis, and suggest a therapy algorithm for the treatment of skin sarcoidosis.


The frequency of the second mesiobuccal canal in maxillary first molars among a sample of the Kurdistan Region-Iraq population - A retrospective cone-beam computed tomography evaluation.
One of the most complexes in root and canal anatomy is the maxillary first permanent molar. This study aimed to analyze the frequency of mesiobuccal (MB2) canal and its apical portals of exit, in patients belonging to different gender-age groups and determine the possible relation with sex and age. A CBCT scan images were accessed from a documented database of 343 patients (178 male, 165 female), who had an oral and maxillofacial examination. The age of the patients ranging from 12 to 63 years. The frequency of the MB2 canal and its portals of exit apically were observed. Age and gender correlation were calculated using the χ2 test. P < 0.05 was considered significant. A total of 634 maxillary first molars (335 male, 299 female) were included. The MB2 canal was found in 53.78% of the cases. A significantly higher incidence of the MB2 canal was detected in males than in females. No correlation in the presence and/or absence of the MB2 canal in terms of age. When MB2 canal present, a single apical foramen was observed in 66.28% of the cases, two apical foramina were present in 33.72% of the cases. MB2 canals may be present in approximately half of the cases, from which one third of the cases have their own apical portal of exit.


[Investigations on suckling piglets castrated under automated isoflurane anesthesia].
Investigation of defensive reactions, piglet losses, post-bleeding and recovery time of suckling piglets castrated under automated isoflurane anesthesia as well as measurements of isoflurane concentrations in ambient air and estimation of the cleaning and disinfection success of anesthesia masks. A total of 955 suckling piglets (age: 4.0 ± 1.2 days; weight: 2.0 ± 0.5 kg) were castrated under automated isoflurane anesthesia (PorcAnest 3000®) after the administration of a non-steroidal anti-inflammatory drug. Reactions during the procedure were assessed before castration using the interdigital claw reflex and during castration by defensive movements and vocal response. The piglets' recovery time was evaluated in the stable corridor (pass 1) and the farrowing pen (passes 4-5). In 73 animals, the spermatic cord was cut with a scalpel and the post-operative bleeding visually evaluated. In addition, exposure measurements of isoflurane were performed and anesthetic masks were examined for total bacterial contamination and indicator bacteria before and after the anesthetic procedure and following their disinfection. Following insufflation of isoflurane for 90 seconds 94.3 % of the piglets and after prior testing of the interdigital claw reflex and possible extension of the anesthetic supply 95.3 % of the piglets showed no or minimal defensive movements during castration. An anesthetic incident occurred in 0.9 % of the piglets, but no animal died. The recovery time lasted 7.3 ± 4.7 minutes (pass 1) and 6.2 ± 3.3 minutes (passes 4-5). Cutting the spermatic cord with a scalpel led to a higher post-bleeding score (p < 0.001) compared to use of the emasculator. Isoflurane concentrations in ambient air ranged between 4.5 und 28.1 mg/m3. Masks disinfection reduced the total germ count by 99.8 %. Contaminations with Escherichia coli and MRSA were no longer detectable in 4 of 6 cases after disinfection. Isoflurane anesthesia led in over 94 % of the piglets to no or minimal defensive reactions during castration. Anesthetic incidents occurred rarely and no piglet losses were recorded. Therefore, automated isoflurane anesthesia is associated with a low risk for suckling piglets. Measurements of isoflurane concentrations on persons involved were below the internationally lowest limit value. Disinfection of the anesthesia masks may prevent germ transmission between animal groups via this potential vector.


Intravenously administered cloxacillin-induced neutropenia with eosinophilia in a patient with infective endocarditis: a case report.
Bacteremia following Staphylococcus aureus is a serious clinical condition which is often associated with distant metastatic infections. One of the most dreaded complications of Staphylococcus aureus bacteremia is infective endocarditis. Cloxacillin is a common antibiotic prescribed for suspected staphylococcal infections and confirmed methicillin-sensitive Staphylococcus aureus infections. Prolonged use of cloxacillin may lead to neutropenia. A 38-year-old Sinhalese man presented to Teaching Hospital Kurunegala, Sri Lanka, complaining of a 3-week history of fever; he was found to have a pansystolic murmur over the apex of his heart. He had leukocytosis with predominant neutrocytosis. His C-reactive protein was 231 mg/l and erythrocyte sedimentation rate was 100 mm/first hour. Transthoracic two-dimensional echocardiography revealed prolapsed mitral valve with 7 × 13 mm vegetation over the posterior mitral valve. On the following day, three blood cultures became positive and were subsequently identified as Staphylococcus aureus. Intravenously administered cloxacillin 3 g 6 hourly was started. Following day 24 of intravenously administered cloxacillin, our patient developed high spike fever. His total white blood cells were: 990/mm3 with 34% neutrophils and 22% eosinophils. His hemoglobin concentration was 9.5 g/dL and platelet count remained normal (202 × 106/mm3). His C-reactive protein was 78 mg/l, erythrocyte sedimentation rate was 95 mm/first hour, and he was otherwise comfortable, showing no signs of sepsis beside the high grade fever. His serum was negative for filarial and Toxoplasma antibodies while stool was negative for oocytes and amoebic cysts. Further, his serum was negative for dengue virus, Epstein-Barr virus, cytomegalovirus, and hepatitis B antibodies. He was clinically well on day 6 after stopping cloxacillin with 44% neutrophils and 18% eosinophils. His C-reactive protein and erythrocyte sedimentation rate became normal, and there was no further plan for cardiothoracic intervention or administration of antimicrobials. He was discharged from hospital and remained well 6 months later. This case report signifies the potential fatal adverse effect of cloxacillin in methicillin-sensitive Staphylococcus aureus infections. Leukopenia is associated with prolonged use of high doses of cloxacillin. In addition to transthoracic two-dimensional echocardiography and inflammatory markers, sequential white blood cells and differential counts would help clinicians to assess the prognosis of patients with infective endocarditis.


Lack of association between microRNA-137 SNP rs1625579 and schizophrenia in a replication study of Han Chinese.
Schizophrenia (SCZ) is a common, complex and severe psychiatric disorder associated with many different genetic and environmental risk factors. A recent genome-wide association study identified a single-nucleotide polymorphism (SNP, rs1625579) in microRNA-137 (miR-137) as a possible susceptibility locus for SCZ. Hoping to validate this finding, we conducted a case-control study of the Han Chinese population, with 506 SCZ cases and 522 healthy controls, using the Ligase detection reaction-polymerase chain reaction method to genotype the polymorphism rs1625579 in the miR-137 gene. However, we found no significant difference (P > 0.05) in either allele or genotype frequency in this SNP between patients and controls. In addition, a meta-analysis indicated that the 'T' allele of SNP rs1625579 was not associated with susceptibility to SCZ in Han Chinese populations (pooled OR 1.087, 95 % CI 0.847-1.396, P = 0.512). Thus, these results do not support the previous finding suggesting further replication studies using a large-scale association analysis that should be warranted in Han Chinese populations.


Lead inhibits the basal and stimulated responses of a rat osteoblast-like cell line ROS 17/2.8 to 1 alpha,25-dihydroxyvitamin D3 and IGF-I.
Low-level exposure to lead impairs longitudinal growth in children and in experimental animals. The proposed mechanisms include decreased osteocalcin secretion in response to 1 alpha,25-(OH)2 vitamin D3 and decreased response to insulin-like growth factor-I. The interaction of lead, 1 alpha,25-(OH)2 vitamin D3, and insulin-like growth factor-I was investigated in an osteoblast-like cell line from rat osteosarcoma, ROS 17/2.8. Cells were cultured 24 hr in a serum-free medium with lead, 1 alpha,25-(OH)2 vitamin D3, and insulin-like growth factor-I. 1 alpha,25-(OH)2 vitamin D3 (10 nM) evoked a 4-5 X increase in osteocalcin secretion and a 100% increase in cellular alkaline phosphatase activity but no increase in DNA/cell layer. Insulin-like growth factor-I (92.5 ng/ml) evoked a 100% increase of osteocalcin secretion and a 20% increase in cellular DNA contents but no change in cellular alkaline phosphatase activity. Basal and stimulated cellular osteocalcin secretion, cellular alkaline phosphatase activity, and DNA contents were significantly inhibited by addition of 1-10 microM lead. The data are consistent with a toxic effect of lead on osteoblastic function and the cellular responses to 1 alpha,25-(OH)2 vitamin D3 and insulin-like growth factor-I. This interaction may be relevant to impaired childhood growth at low levels of lead exposure.


Genome sequence of the plant growth-promoting rhizobacterium Pseudomonas putida S11.
Here we report the genome sequence of a plant growth-promoting rhizobacterium, Pseudomonas putida S11. The length of the draft genome sequence is approximately 5,970,799 bp, with a G+C content of 62.4%. The genome contains 6,076 protein-coding sequences.


Clinical study of central taste disorders and discussion of the central gustatory pathway.
The aim of this work is to examine the clinical findings of patients with taste disorders due to central lesions and also to study the central gustatory pathway in humans. We conducted a retrospective review of 13 patients with central taste disorders that visited Nihon University Itabashi Hospital. An additional 25 cases with central taste disorders previously reported in the literature were assessed in the study. We examined 38 patients with taste disorders due to central lesions. The sites of the central lesions and their frequencies, the laterality of taste disorders relative to the central lesions, and prognosis of taste disorders were studied. We identified the following taste-related regions in the central nervous system: the medulla, pons, midbrain, thalamus, internal capsule, putamen, corona radiata, and cerebral cortex. As for the laterality of the taste disorders, we observed more ipsilateral cases for lesions located from the medulla to the pons. We observed ipsilateral, contralateral, and bilateral cases for lesions located above the midbrain, but bilateral cases were more frequently detected. Taste disorders of 80% of the patients improved by 24 weeks. The prognoses of central taste disorders appeared to be good. We identified eight central regions supposed to be relate to taste disorders. From the laterality of the taste disorders relative to the central lesions, it was suggested that the central gustatory pathway ascends ipsilaterally from the medulla to the pons, branches at the upper pons, and then ascends bilaterally from the midbrain to the cerebral cortex.


New anti-platelet agents: the end of resistance?
Despite improved clinical outcomes from dual anti-platelet therapy with aspirin plus the CYP12 ADP receptor antagonist clopidogrel in patients undergoing coronary revascularisation, ex-vivo platelet function testing consistently reveals a proportion of patients with apparent resistance or non-response to clopidogrel loading and maintenance therapy who are at increased risk of coronary thrombosis. Treatment regimens using the newer CYP12 antagonists prasugrel and ticagrelor demonstrate improved ex-vivo platelet inhibition and superior clinical efficacy in large-scale clinical trials-even in patients demonstrating clopidogrel resistance. However, improved efficacy comes at the cost of an increased overall risk of bleeding for both drugs. Further analysis of the outcomes from large scale clinical studies suggests that individual patient sub-groups differ both in their liklehood of bleeding with newer anti-platelet agents and with regard to efficacy outcomes. Therefore when deciding anti-platelet regimens in suspected acute coronary syndrome, particular consideration must be given to patient's risk of thrombosis (STEMI, previous stent thrombosis), the procedure (complex PCI, thrombus in-situ, strategy of pre-treatment), and factors affecting safety (patient age, patient weight, previous stroke, liklehood of surgical revascularisation). Placing the focus on individualised patient risk-benefit assessment with appropriate use of platelet function testing when indicated, in combination with the ongoing assessment of prasugrel and ticagrelor in larger numbers of patients should be the key strategies governing use of dual anti-platelet therapy.


Lecithin liposomes and microemulsions as new chromatographic phases.
Lecithins are phospholipidic mixtures that can be part of microemulsions and liposomes. In this work, ready-to-use preparations of lecithin have been tested as pseudostationary and mobile phases in EKC and LC, respectively. The selectivity of two EKC systems, one based on lecithin microemulsions (LMEEKC) and another on liposomes (LLEKC), and of a LC system based on lecithin microemulsions (MELC) has been evaluated through the solvation parameter model. In all cases, solute volume and hydrogen-bond basicity are the main descriptors that drive the partition process. While solute volume favors the retention of solutes, hydrogen-bond basicity has the contrary effect. In lecithin-based EKC systems the hydrogen-bond acidity of the solute leads to a higher retention while in the lecithin-based LC system a minor retention is produced. The three lecithin systems have been compared through the solvation parameter model to other chromatographic systems, most of them containing phospholipids. Principal component analysis reveals that lecithin systems cluster together with the other EKC systems based on phospholipids, with an immobilized artificial membrane (IAM) LC system, with the octanol/water reference partition system, and with a SDS-based microemulsion. Thus, they all show similar selectivity. However, the great advantage of using the ready-to use lecithin systems is that the laborious liposome preparation is avoided, and that their commercial availability makes them more affordable than IAM LC columns. Finally, taking into account that lecithin has a high semblance to the mammalian cell membranes composition, the ability of the three lecithin systems to mimic the pass of the solutes through the membranes has been evaluated. Experimental determinations have demonstrated that the skin partition of neutral solutes can be easily emulated, especially using the lecithin-microemulsion EKC method. The model is robust and shows good prediction ability.


Comorbidity of depression and anxiety leads to a poor prognosis following angina pectoris patients: a prospective study.
Depression and anxiety are two common mood problems among patients with cardiovascular disease (CVD) and are associated with poor cardiac prognoses. The comorbidity of depression and anxiety is considered to be a more severe psychological status than non-comorbid mood disorders. However, little is known about the relationship between depression or anxiety and noncardiac readmission. We conducted a prospective study on the prognostic impact of depression, anxiety, and the comorbidity of the two among angina pectoris (AP) patients. In this prospective study, 443 patients with AP were included in the analysis. Follow-up assessments were performed 1 year, and 2 years after patient discharges. Clinical outcomes of interest included noncardiac readmission, major adverse cardiovascular events (MACEs), and composite events. Depression and anxiety symptom scores derived from the patient health questionnaire-9 (PHQ-9) and generalised anxiety disorder-7 (GAD-7) questionnaire were used to assess mood symptoms at baseline. Participants with symptom scores of ≥10 on both the depression and anxiety questionnaires formed the clinical comorbidity subgroup. We used multivariable Cox proportional hazards models to evaluate the impact of individual mood symptom and comorbidity on clinical outcomes. Among all the AP patients, 172 (38. 9%) were determined to have depression symptoms, 127 (28.7%) patients had anxiety symptoms and 71 (16.0%) patients suffered from their comorbidity. After controlling covariates, we found that patients who endured clinical depression (hazard ratio [HR] = 2.38, 95% confidence interval [CI] 1.06-5.33, p = 0.035) and anxiety ([HR] 2.85, 95% [CI] 1.10-7.45, p = 0.032) had a high risk of noncardiac readmission. Compared to participants with no mood symptoms, those with clinical comorbidity of depression and anxiety presented a greater risk of noncardiac readmission ([HR] 2.91, 95% [CI] 1.03-8.18, p = 0.043) MACEs ([HR] 2.38, 95% [CI] 1.11-5.10, p = 0.025) and composite event ([HR] 2.52, 95% [CI] 1.35-4.69, p = 0.004). Depression and anxiety were found to have predictive value for noncardiac readmission among patients with AP. Furthermore, prognoses were found to be worse for patients with comorbidity of depression and anxiety than those with single mood symptom. Additional attention needs to be focused on the initial identification and long-term monitoring of mood symptom comorbidity.


Optimizing dosimetry with high-dose intracoronary gamma radiation (21 Gy) for patients with diffuse in-stent restenosis.
The efficacy of intracoronary gamma radiation (IRT-gamma) in reducing recurrent in-stent restenosis (ISR) is well established using doses of 14-18 Gy. We sought to examine whether an escalation in dose to 21 Gy is safe and confers additional benefit in reducing repeat revascularization and major adverse cardiac events (MACE) in patients with diffuse ISR. Forty-seven patients with diffuse ISR (lesion length 20-80 mm) in native coronary arteries (n=25) and saphenous vein grafts (n=22) underwent percutaneous transluminal coronary angioplasty and/or additional stents followed by IRT-gamma using the Checkmate system (Cordis) with a dose of 21 Gy. All patients were discharged with clopidogrel for 12 months and aspirin indefinitely. Six-month angiographic and 12-month clinical outcomes of these patients were compared to 120 patients treated with 18 Gy using the same system. At baseline, patients in the 21-Gy group had more multivessel, vein graft disease and history of prior myocardial infarctions and coronary artery bypass grafts (P<.001). The use of debulking devices and stents was less in this group (P<.001). Procedural and in-hospital complications were similar. Follow-up at 6 months revealed nonsignificant but lower late loss (in-stent, 0.33+/-0.7 mm; in-lesion, 0.41+/-0.6 mm) in the 21-Gy group compared to the 18-Gy group; follow-up at 12 months revealed a trend toward less overall myocardial infarction, although repeat revascularization and MACE rates were similar. IRT-gamma therapy for diffuse ISR lesions with a 21-Gy dose is clinically safe and feasible with marked reduction in late loss but does not confer additional benefit with regard to repeat revascularization and MACE when compared to a dose of 18 Gy.


Ethanolic Hwaeumjeon induces mitochondrial dependent apoptosis partly via PI3K/AKT/HSP27/ERK pathways and inhibits PSA and AR in LNCaP cells.
Hwaeumjeon is a classical prescription that has been traditionally used for treatment of urogenital diseases with no scientific evidences until now. Thus, the present study was performed to evaluate antitumor mechanism of ethanolic Hwaeumjeon (EHEJ). 2-Dimensional electrophoresis (2-DE) proteomic analysis, cell culture study, and Western blotting on apoptosis and prostate-specific antigen (PSA) related proteins were carried out in LNCaP prostate cancer cells. Eight spots with significant increased or decreased expression revealed by 2-DE based comparative proteomic analysis were identified as an increased protein ENC-1AS, four decreased proteins such as RAB34, SFRS1, heat shock 27, and proteasome activator, and three novel proteins such as Rho GDP dissociation inhibitor alpha, cytoplasmic antiproteinase, and EIF3EIP protein in EHEJ-treated LNCaP cells. In addition, EHEJ selectively inhibited the growth of LNCaP prostate cancer cells compared to normal human umbilical vein endothelial cells. Furthermore, EHEJ inhibited PSA and androgen receptor (AR) expression in androgen sensitive LNCaP prostate cancer cells at nontoxic concentrations. Also, EHEJ increased sub-G1 apoptotic portion, activated caspase-9 and -3, cleaved poly (ADP-ribose) polymerase (PARP) and increased the ratio of Bax to Bcl-2. Interestingly, EHEJ also attenuated phosphatidylinositol-3 kinase (PI3K) expression and suppressed the phosphorylation of survival gene AKT, ERK, and HSP27 in LNCaP cells. Consistently, PI3K and ERK inhibitors potentiated EHEJ-induced cytotoxicity and overexpression of Bcl-2 attenuated EHEJ-mediated apoptosis in LNCaP cells. These findings suggest that EHEJ induces mitochondrial dependent apoptosis partly via PI3K/AKT/HSP27/ERK pathways and inhibits PSA and AR in LNCaP cells as a prostate cancer chemopreventive candidate.


Potential impact of physical distancing on physical and mental health: a rapid narrative umbrella review of meta-analyses on the link between social connection and health.
The imperative for physical distancing (mostly referred to as social distancing) during COVID-19 pandemic may deteriorate physical and mental health. We aimed at summarising the strength of evidence in the published literature on the association of physical and mental health with social connection via social isolation, living alone and loneliness. We conducted a systematic search in April 2020 to identify meta-analyses using the Medline, PsycINFO and Web of Science databases. The search strategy included terms of social isolation, loneliness, living alone and meta-analysis. Eligible meta-analyses needed to report any sort of association between an indicator of social connection and any physical or mental health outcome. The findings were summarised in a narrative synthesis. Twenty-five meta-analyses met our criteria, of which 10 focused on physical health and 15 on mental health outcomes. The results suggest that lack of social connection is associated with chronic physical symptoms, frailty, coronary heart disease, malnutrition, hospital readmission, reduced vaccine uptake, early mortality, depression, social anxiety, psychosis, cognitive impairment in later life and suicidal ideation. The existing evidence clearly indicates that social connection is associated with a range of poor physical and mental health outcomes. A potential negative impact on these outcomes needs to be considered in future decisions on physical distancing measures.


Sterile subperiosteal fluid collections accompanying orbital wall infarction in sickle-cell disease.
Infarction of the orbital wall is an uncommon manifestation of sickle cell disease (SCD) that may mimic an infectious process. We report a patient with two separate orbital infarctions with different presenting symptoms involving different bones. Radiologic-guided sampling of a periosteal fluid collection in the first episode showed likely sterile inflammatory exudates. This case highlights the range of findings in orbital wall infarction in SCD as well as helpful clinical and imaging entities that may differentiate infarction from infection, allowing early diagnosis and appropriate management.


Selection for Cheaper Amino Acids Drives Nucleotide Usage at the Start of Translation in Eukaryotic Genes.
Coding regions have complex interactions among multiple selective forces, which are manifested as biases in nucleotide composition. Previous studies have revealed a decreasing GC gradient from the 5'-end to 3'-end of coding regions in various organisms. We confirmed that this gradient is universal in eukaryotic genes, but the decrease only starts from the ∼ 25th codon. This trend is mostly found in nonsynonymous (ns) sites at which the GC gradient is universal across the eukaryotic genome. Increased GC contents at ns sites result in cheaper amino acids, indicating a universal selection for energy efficiency toward the N-termini of encoded proteins. Within a genome, the decreasing GC gradient is intensified from lowly to highly expressed genes (more and more protein products), further supporting this hypothesis. This reveals a conserved selective constraint for cheaper amino acids at the translation start that drives the increased GC contents at ns sites. Elevated GC contents can facilitate transcription but result in a more stable local secondary structure around the start codon and subsequently impede translation initiation. Conversely, the GC gradients at four-fold and two-fold synonymous sites vary across species. They could decrease or increase, suggesting different constraints acting at the GC contents of different codon sites in different species. This study reveals that the overall GC contents at the translation start are consequences of complex interactions among several major biological processes that shape the nucleotide sequences, especially efficient energy usage.


FoxO1-mediated inhibition of STAT1 alleviates tubulointerstitial fibrosis and tubule apoptosis in diabetic kidney disease.
Tubulointerstitial fibrosis (TIF) plays an important role in the progression of diabetic kidney disease (DKD). Forkhead box O1 (FoxO1) is involved in the regulation of metabolism and cell apoptosis, but its function in renal TIF induced by DKD is less well understood. Human kidney biopsies with DKD and normal controls were used to detect apoptosis and TIF induced by diabetes. A mouse model with kidney-specific overexpression of Pax2-3aFoxO1 was established to further investigate the functions of FoxO1 in vivo. The in vitro roles of FoxO1 were analyzed in HK-2 cells with 3aFoxO1-knockin (3aFoxO1-KI) or FoxO1-knockdown (FoxO1-KD) via CRISPR/Cas9. Western blot, immunohistochemistry, and chromatin immunoprecipitation were used to explore the underlying mechanisms. In this study, DKD patients had increased renal TIF and apoptosis. In vivo study showed that kidney-specific overexpression of Pax2-3aFoxO1 significantly reduced the expression of p-STAT1 with resultant renal functional impairment, retarding renal TIF and apoptosis in diabetic mice. Meanwhile, We observed that FoxO1-KD in HK-2 cells aggravated the expression of p-STAT1, leading to activation of epithelial-to-mesenchymal transition (EMT) and intrinsic apoptotic pathway. Conversely, EMT and apoptosis were significantly attenuated in HK-2 cells with 3aFoxO1-KI under hyperglycemic conditions. Taken together, these data suggest that the protection role of FoxO1 against renal TIF and apoptosis in DKD is likely in part to target STAT1 signaling, which may be a promising strategy for long-term treatment of DKD. FUND: This work was supported by grants from the National Natural Science Foundation of China (grant numbers: 81570746 and 81770812).


Benthic marine litter in the coastal zone of Bejaia (Algeria) as indicators of anthropogenic pollution.
We studied the abundance of seafloor litter in the bay of Bejaia, Algeria, in order to better understand its sources and distribution and provide scientists with the technical basis for further monitoring and reduction measures. Data were collected during trawl surveys dedicated to fishing activity, between 40 and 200m. After each trawl, litter items were manually sorted and analyzed. The highest concentration of 58,998 items/ha was recorded to the east of the bay. Overall, plastic was the dominant component of the litter with 88% of the total amount, in weight. Most of the waste was of terrestrial origin, with rivers and beaches being the main sources due to population density, highly developed tourism during the summer season, and inadequate waste management. Overall, the results provide relevant benchmarks for future monitoring and are discussed in terms of poor waste management, a critical issue in the region.


Effects of physical training on ventilatory equivalent and respiratory exchange ratio during weight supported, steady-state exercise.
Thirty-three college men participated in a 9-week endurance training program. An equal number of subjects served as controls. Pre- and post-test metabolic measurements were made during 10 min of submaximal exercise (1080 kpm/min at 60 rpm) and 15 min of recovery. Measurements included oxygen consumption, CO2 production, ventilatory equivalent (Ve/VO2 ratio) and respiratory exchange ratio (R). A three factor design variance analysis was used to analyze the effects of training on min-by-min exercise and recovery Ve/VO2 ratio and R. For the experimental group training resulted in a significant improvement in ventilatory efficiency during exercise, as well as a significant decrease in R. During recovery, Ve/VO2 and R decreased significantly for both groups although the magnitude of change was greater for the group that trained. Apparently, there was a significant habituation effect due to test procedures for the control group. The results are discussed in terms of lactate production and substrate utilization during exercise.


Twelve different enzyme assays on dried-blood filter paper samples for detection of patients with selected inherited lysosomal storage diseases.
Diagnoses of inherited lysosomal storage diseases are based on specific enzymatic assays performed on plasma, leukocytes, fibroblasts, and lately, dried-blood filter paper samples. We evaluated feasibility of detecting of patients with several inherited lysosomal storage diseases using dried-blood filter paper samples for appropriate enzyme assays. Fluorometric methods were used to evaluate the activities of arylsulfatase B, alpha-N-acetylglucosaminidase, chitotriosidase, alpha and beta-galactosidases, beta-glucosidase, beta-glucuronidase, total hexosaminidases, hexosaminidase A, alpha-iduronidase, and iduronate-2-sulfatase. A radiometric method was used for sphyngomyelinase determination. Single 3.0-mm diameter disks containing dried-blood samples were incubated at 37 degrees C with appropriate dilution buffers and artificial substrates, and the fluorescence or radioactivity was measured. Our results showed a statistically significant difference of the enzyme activity between affected individuals and controls, in all the assays performed. In contrast, we have not obtained a complete differentiation between heterozygotes and controls with these assays. Enzyme assay on dried-blood filter paper is a suitable method to screen for several lysosomal storage diseases. Despite the low individual incidence of these pathologies, the incorporation of individual enzyme assays in neonatal screening programs could be justified to screen for diseases with relatively high local frequency and therapeutic measures available.


The sustainability of rice-crayfish coculture systems: a mini review of evidence from Jianghan plain in China.
Rice-crayfish coculture (RC) uses 10% of the paddy field area for crayfish ditches, with rice cultivated in the remaining area, providing staple carbohydrates alongside fish rich in protein and essential oils. These systems rely on complex interactions, involving nutrient cycling, fish feeding, soil physicochemical modification, and insect-pest predation, and have important socio-economic effects. Past studies have considered only one or a few of these aspects pertinent to food system sustainability, and there remains a need for an integrated assessment of RC systems. In this mini-review, we collate data from two field experiments and three field surveys published across eight papers to synthesize the overall sustainability of RC systems in Jianghan Plain in China. In deep groundwater fields, the RC rice yield was 30-55% lower than for typical rice-rapeseed (RR) rotations, while CH4 emission and pesticide use were 41-96% and 50% lower, respectively. In shallow groundwater fields, RC rice yield was similar to typical rice monoculture (RM) cultivation, while CH4 emission and pesticide use were 28-41% and 17% lower for RC cultivation. Field survey data indicated that RC can improve soil nutrient and organic matter content significantly compared with RM cultivation, and also increase the diversity of fauna and flora in the paddy field whilst reducing the incidence of chilo suppressalis (a major rice pest). Feed inputs to RC systems increased crayfish yield by 31-71% and reduced the fraction of N inputs lost to the environment from 71% to 41%. We conclude that RC systems with feed inputs in areas with shallow groundwater can deliver improved food security, sustainability, and resilience through ecological intensification. © 2020 Society of Chemical Industry.


Long-term stability of subtypes in schizophrenic disorders: a comparison of four diagnostic systems.
The long-term stability of subtypes of schizophrenic disorders in 148 narrowly defined schizophrenic patients according to four diagnostic systems was compared. The patients were investigated longitudinally for 23 years on average (range 10-50 years). Patients who experienced only one episode and those who were permanently hospitalised were excluded on methodological grounds. Of the remaining 100 patients, a total of 461 episodes were classified into various subtypes according to the criteria of DSM-III-R, ICD-10, the positive/negative dichotomy, and Schneider's first-rank symptoms. It was found that long-term stability of subtype in schizophrenic disorder was not the rule but the exception. The frequency of stable course was found to be depend on the type of the initial episode. In most cases a subtype change occurred within the first few years of the illness with no clear direction. In later stages of the illness the relative frequency of episodes predominated by negative symptomatology increased. The findings were similar for DSM-III-R, ICD-10 and positive/negative dichotomy. Only in patients beginning without first-rank symptoms were more stable than non-stable courses found. The results of this study do not support the assumption that stable subtypes are nosological or etiopathogenetic subentities of schizophrenic disorders.


Prevalence and correlates of depressive symptoms in Chinese older adults: a population-based study.
In China, the rapid socioeconomic transition and the consequential traditional culture change had significant influences on Chinese older-adult depression. In the present study, the prevalence, the potential risk, and the protective factors of depression in the Chinese older population were investigated. A cross-sectional survey was conducted with a nationwide representative Chinese sample of 4945 older adults; the Center for Epidemiologic Studies Depression Scale (CES-D) was used as the measurement tool for depressive symptoms. Demographic and other self-reported related factors were taken into consideration. The prevalence of self-reported depressive symptoms (CES-D ≥ 16) in the total study population was 39.86% (pre-old: 39.95%, young-old: 39.84%, old-old: 39.65%, oldest-old: 45.19%); CES-D score was significantly higher in the oldest-old group than in the three younger groups. Furthermore, multiple regression analysis indicated that age itself was not an effective predictor for depressive symptoms, whereas family support and health status explained most of the variation. The present study found a higher prevalence of depression in the Chinese older population compared with those reported two decades ago. Family support and health status were the most significant protective factors for depression in Chinese older adults. Traditional Chinese culture, which values family significantly and contributed to the previously reported lower prevalence rate, changed dramatically, which may explain the current higher prevalence. In addition to the deterioration of family support, the worsening of health status is another significant factor.


Correlation of MR changes with Doppler US measurements of blood flow in exercising normal muscle.
Muscle data from phosphorus-31 magnetic resonance (MR) spectroscopy and hydrogen-1 MR imaging and popliteal artery data from duplex Doppler ultrasound were compared during an exercise test of the anterior compartment of the leg, in nine healthy volunteers. Significant variations (mean +/- standard deviation) were observed at the end of exercise versus rest in intracellular pH (pHi) (6.32 +/- 0.02 vs 7.02 +/- 0.04, P < .001), T2 (38.2 msec +/- 2.3 vs 29.5 msec +/- 1.1, P < .001), and popliteal output (652 mL/min +/- 232 vs 149 mL/min +/- 65, P < .001). These variables showed the following significant correlations at the end of exercise: T2 and pHi (r = -.784, P < .01), T2 and popliteal output (r = .737, P < .03), and pHi and popliteal output (r = -.902, P < .001). However, during recovery, the T2 curve was significantly different from those of pHi and popliteal output. This suggests that even if circulatory conditions play a role in the maximum T2 variation during exercise, they do not directly explain T2 changes. Furthermore, the correlations involving pHi suggest the role of the metabolism of exercising muscle in transcapillary fluid movement.


Impact of Bleeding on Myocardial Infarction, Stroke, and Death During 12 Months Dual Antiplatelet Therapy After Acute Coronary Syndrome.
Bleeding remains a complication during dual antiplatelet therapy (DAPT) for acute coronary syndrome (ACS). Some data suggest a link between bleeding and worsened vascular outcomes. However, this association is unclear, due to omitting of minor bleedings when applying conservative scales. In contrast, the Platelet Inhibition and Outcomes (PLATO) trial classification used broad realistic capturing of all bleedings. Access was gained to the Food and Drug Administration-issued adjudication data set on which post hoc analyses of bleeding, myocardial infarction (MI), stroke, and death were conducted. Bleeding was defined as minimal, minor, major, and life-threatening or fatal (LTOF) as per the original PLATO scale. Among 18,624 enrollees, 10,705 adjudicated events occurred across 7171 patients. There were 618 minimal, 1412 minor, 1216 major, and 536 LTOF bleedings for the total of 3782 events reported in 3387 patients. There were 938 deaths, 2751 MIs and 359 strokes. The overall bleeding was 20.3%, exhibited in 19.2% patients. Total bleeds were associated with less deaths (odds ratio [OR]: 0.55, 95% confidence interval [CI]: 0.47-0.63) and MI (OR: 0.47, 95% CI: 0.41-0.54; P < .001 for both). There were no differences in deaths (OR: 1.11, 95% CI: 0.93-1.34; P = .24), but less MIs (OR: 0.72. 95% CI: 0.59-0.86; P < .001), and more strokes (OR: 2.17, 95% CI: 1.64-2.88; P < .001) after LTOF. Major, minor, and minimal bleeds were associated with less deaths and MI but not strokes. These large uniformly adjudicated data reveal that within 12 months of dual antiplatelet therapy, 1 out of 5 patients experiences bleeding. Overall, bleeding was associated with diminished incidence of death and MI but not strokes.


Quiet eye and the Bereitschaftspotential: visuomotor mechanisms of expert motor performance.
Concurrent exploration of the Bereitschaftspotential (BP) and quiet eye period (QE) was implemented to assess potential mechanisms underlying psychomotor skills that differentiate expert and near-expert performers. Twenty golfers were classified by their USGA handicap rating as either a high handicap (HH; near-expert) or low handicap (LH; expert) to permit skill-based inferences. Participants completed 90 trials during which QE duration, BP activity, and putting performance were recorded. The application of single-subject analyses illustrated that LH golfers were more accurate and less variable in their performance than the HH group. Systematic differences in QE duration and BP were also observed, with experts exhibiting a prolonged quiet eye period and greater cortical activation in the right-central region compared with non-experts. A significant association between cortical activation and QE duration was also noted. The results of this investigation lend support to the motor programming/preparation function of the QE period. Practical and theoretical implications are presented and suggestions for future empirical work provided.


Development and Validation of a Simple-to-Use Nomogram for Predicting the Upgrade of Atypical Ductal Hyperplasia on Core Needle Biopsy in Ultrasound-Detected Breast Lesions.
The rate of carcinoma upgrade for atypical ductal hyperplasia (ADH) diagnosed on core needle biopsy (CNB) is variable on open excision. The purpose of the present study was to develop and validate a simple-to-use nomogram for predicting the upgrade of ADH diagnosed with ultrasound (US)-guided core needle biopsy in patients with US-detected breast lesions. Two retrospective sets, the training set (n = 401) and the validation set (n = 186), from Fudan University Shanghai Cancer Center between January 2014 and December 2019 were retrospectively analyzed. Clinicopathological and US features were selected using univariate and multivariable logistic regression, and the significant features were incorporated to build a nomogram model. Model discrimination and calibration were assessed in the training set and validation set. Of the 587 ADH biopsies, 67.7% (training set: 267/401, 66.6%; validation set: 128/186, 68.8%) were upgraded to cancers. In the multivariable analysis, the risk factors were age [odds ratio (OR) 2.739, 95% confidence interval (CI): 1.525-5.672], mass palpation (OR 3.008, 95% CI: 1.624-5.672), calcifications on US (OR 4.752, 95% CI: 2.569-9.276), ADH extent (OR 3.150, 95% CI: 1.951-5.155), and suspected malignancy (OR 4.162, CI: 2.289-7.980). The model showed good discrimination, with an area under curve (AUC) of 0.783 (95% CI: 0.736-0.831), and good calibration (p = 0.543). The application of the nomogram in the validation set still had good discrimination (AUC = 0.753, 95% CI: 0.666-0.841) and calibration (p = 0.565). Instead of surgical excision of all ADHs, if those categorized with the model to be at low risk for upgrade were surveillanced and the remainder were excised, then 63.7% (37/58) of surgeries of benign lesions could have been avoided and 78.1% (100/128) malignant lesions could be treated in time. This study developed a simple-to-use nomogram by incorporating clinicopathological and US features with the overarching goal of predicting the probability of upgrade in women with ADH. The nomogram could be expected to decrease unnecessary surgery by nearly two-third and to identify most of the malignant lesions, helping guide clinical decision making with regard to surveillance versus surgical excision of ADH lesions.


Predictive models of hypertensive disorders in pregnancy based on support vector machine algorithm.
The risk factors of hypertensive disorders in pregnancy (HDP) could be summarized into three categories: clinical epidemiological factors, hemodynamic factors and biochemical factors. To establish models for early prediction and intervention of HDP. This study used the three types of risk factors and support vector machine (SVM) to establish prediction models of HDP at different gestational weeks. The average accuracy of the model was gradually increased when the pregnancy progressed, especially in the late pregnancy 28-34 weeks and ⩾ 35 weeks, it reached more than 92%. Multi-risk factors combined with dynamic gestational weeks' prediction of HDP based on machine learning was superior to static and single-class conventional prediction methods. Multiple continuous tests could be performed from early pregnancy to late pregnancy.


Nitrative DNA damage in inflammation and its possible role in carcinogenesis.
Chronic inflammation has long been recognized as a risk factor for human cancer at various sites. Examples include Helicobacter pylori-induced gastritis for gastric cancer, inflammatory bowel disease (ulcerative colitis and Crohn's disease) for colorectal cancer and chronic viral hepatitis for liver cancer. Here we review the role in carcinogenesis of nitrative damage to nucleic acids, DNA and RNA, which occurs during inflammation through the generation of reactive nitrogen species, such as peroxynitrite, nitroxyl, and nitrogen dioxide. Enhanced formation of 8-nitroguanine, representative of nitrative damage to nucleobases, has been detected in various inflammatory conditions. The biochemical nature of DNA damage mediated by reactive nitrogen species is discussed in relation to its possible involvement in mutations, genetic instability, and cell death. Better understanding of the mechanisms and role of such nitrative damage in chronic inflammation-associated human cancer is a necessary basis to develop new strategies for cancer prevention by modulating the process of inflammation.


Urantide alleviates monocrotaline induced pulmonary arterial hypertension in Wistar rats.
Pulmonary arterial hypertension (PAH) is a serious disorder with poor prognosis. Urotensin II (UII) has been confirmed to be powerful vasoconstrictor than endothelin-1, which may play an important role in PAH development. The aim of this study is to observe the effects of urantide, a UII receptor antagonist, on monocrotaline (MCT) induced PAH in rats. 60 male Wistar rats were divided into six groups. For early treatment experiment, rats were divided into normal control group, MCT(4w) model group (MCT + saline × 3 wks from the 8th day of MCT injection) and urantide early treatment group (MCT + urantide 10 μg/kg/d × 3 wks, 1 week after MCT injection once). For late treatment experiment, rats were divided as controls, MCT(6w) model group (MCT + saline × 2 wks, 4 weeks after MCT injection once) and urantide late treatment group (MCT + urantide 10 μg/kg/d × 2 wks, 4 weeks after MCT injection once). At the end of experiments, mean pulmonary arterial pressures (mPAP) and mean blood pressure (MBP) of rats in each group were measured by catheterization. Right ventricular weight ratio was also weighed. Relaxation effects of urantide on intralobar pulmonary arterial rings of normal control and MCT(4w) model rats were investigated. Pulmonary artery remodeling was detected by hematoxylin and eosin (HE) staining and immunohistochemistry analysis. Serum nitric oxide (NO) levels in all six groups were assayed by ELISA kits. Urantide markedly reduced the mPAP levels of MCT induced PAH in both early and late treatment groups. It didn't change the MBP. Urantide dose-dependently relaxed the pulmonary arterial rings of normal control and MCT(4w) model rats. Moreover, N(G)-Nitro-l-arginine Methyl Ester (l-NAME) blocked the dilation response induced by urantide. In addition, urantide inhibited the pulmonary vascular remodeling remarkably. Serum NO level elevated in both early and late treatment rats with urantide infusion. These results suggest that urantide effectively alleviated MCT induced rats PAH may through relaxing pulmonary arteries and inhibiting pulmonary vascular remodeling. NO pathway might be one of the mechanisms in urantide induced pulmonary artery dilation. Thus, it is expected that urantide may be a novel therapy for PAH.


Design and Development of the First Peptide-Chelating Bisphosphane Bioconjugate from a Novel Functionalized Phosphorus(III) Hydride Synthon.
Remarkable oxidative stability is shown by the carboxylate-functionalized primary bisphosphane 1. Compound 1 can be used in conjugation reactions with biomolecules for functionalization through the COOH group without prior protection of PH2 groups. A novel water-soluble bisphosphane was obtained by reaction of the PH2 groups of 1 with formaldehyde under mild conditions.


Early infant prefrontal gray matter volume is associated with concurrent and future infant emotionality.
High levels of infant negative emotionality (NE) are associated with emotional and behavioral problems later in childhood. Identifying neural markers of high NE as well as low positive emotionality (PE) in infancy can provide neural markers to aid early identification of vulnerability, and inform interventions to help delay or even prevent psychiatric disorders before the manifestation of symptoms. Prefrontal cortical (PFC) subregions support the regulation of NE and PE, with each PFC subregion differentially specializing in distinct emotional regulation processes. Gray matter (GM) volume measures show good test-retest reliability, and thus have potential use as neural markers of NE and PE. Yet, while studies showed PFC GM structural abnormalities in adolescents and young adults with affective disorders, few studies examined how PFC subregional GM measures are associated with NE and PE in infancy. We aimed to identify relationships among GM in prefrontal cortical subregions at 3 months and caregiver report of infant NE and PE, covarying for infant age and gender and caregiver sociodemographic and clinical variables, in two independent samples at 3 months (Primary: n = 75; Replication sample: n = 40) and at 9 months (Primary: n = 44; Replication sample: n = 40). In the primary sample, greater 3-month medial superior frontal cortical volume was associated with higher infant 3-month NE (p < 0.05); greater 3-month ventrolateral prefrontal cortical volume predicted lower infant 9-month PE (p < 0.05), even after controlling for 3-month NE and PE. GM volume in other PFC subregions also predicted infant 3- and 9-month NE and PE, together with infant demographic factors, caregiver age, and/or caregiver affective instability and anxiety. These findings were replicated in the independent sample. To our knowledge, this is the first study to determine in primary and replication samples associations among infant PFC GM volumes and concurrent and prospective NE and PE, and identify promising, early markers of future psychopathology risk.


Lipoleiomyosarcoma (well-differentiated liposarcoma with leiomyosarcomatous differentiation): a clinicopathologic study of nine cases including one with dedifferentiation.
Leiomyosarcomatous (LMS) differentiation is a rare event in liposarcoma (LPS) and may consist of either well-differentiated liposarcoma (WDL) with an intrinsic smooth muscle component, so-called "lipoleiomyosarcoma," (L-LMS) or dedifferentiated liposarcoma having smooth muscle differentiation in the dedifferentiated zones. The latter are high-grade sarcomas, whereas the behavior of the former group is uncertain. Specifically, it is not clear whether the presence of LMS negatively affects the prognosis. We present our experience with nine cases, the largest to date. The patients (seven male, two female) ranged in age from 42 to 65 years (mean 54 years). The tumors were usually large (2 to >40 cm [mean 17 cm]) tumors in the retroperitoneum (two cases), paratesticular-inguinal region (three cases), mediastinum (one case), lung (one case), abdomen (one case), and popliteal fossa (one case). The nine cases qualified as L-LMS and showed typical WDL with a multifocal, gradual transition into smooth muscle areas. The latter areas accounted for a variable portion of the lesions (range 5-90%) and were of low cellularity, mild to moderate nuclear atypia, and low mitotic activity. These areas seemed to arise from or blend with the smooth muscle in the walls of large vessels within the tumor. One case showed areas of dedifferentiation consisting of actin and desmin-negative, high-grade sarcoma. Follow-up in seven cases (range 26-312 months; mean 119 months) showed multiple local recurrences in seven patients and no metastases. Three patients are currently without evidence of disease (follow-up duration 26-312 months; mean 144 months) and four patients are alive with progressive disease (follow-up duration 60-132 months; mean 99 months). Our study suggests that L-LMS is a dual lineage sarcoma as evidenced by the fact that the smooth muscle component is often multifocal, not necessarily found in close association with the atypical changes in fat, and seemingly originates from atypical ("in situ") changes in the vessel wall. The LMS component, which is typically low grade, does not adversely affect the overall behavior of the tumor, which is similar to that of conventional WDL. LMS in L-LMS should not be misconstrued as evidence of low-grade dedifferentiation, a phenomenon that identifies a more unstable and potentially metastasizing lesion.


The association between biomass fuel use for cooking and linear growth in young children in Bhaktapur, Nepal.
There are still many people in the world who prepare their meals on open fires or stoves using solid fuels from biomass, especially in low-and middle-income countries. Although biomass cooking fuels have been associated with adverse health impacts and diseases, the association with child linear growth remains unclear. In a cohort design, we aimed to describe the association between the use of biomass cooking fuels and linear growth in children aged 18-23 months living in the urban and peri-urban community of Bhaktapur, situated in the Kathmandu valley in Nepal. Caretakers of 600 marginally stunted children aged 6-11 months were interviewed about their source of cooking fuel and other socio-demographic characteristics at enrolment into a randomized controlled trial. Children's body length was measured when children were 18-23 months old. In linear regression models, we estimated the association between the use of biomass fuel and length-for-age Z-scores (LAZ), adjusted for relevant confounders. We repeated these analyses in pre-defined sub-groups and different percentiles of LAZ using quantile regression models. Among study participants, 101 (18%) used biomass as cooking fuel. The association between biomass fuel and LAZ was not statistically significant in the full sample (adjusted regression coefficient: -0.14, 95% CI: -0.28, 0.00). The association was stronger in some of the sub-groups and in the lower tail of the LAZ distribution (those who are stunted), but neither reached statistical significance. Children from households in poor, urban neighborhoods in Nepal which used biomass fuel for cooking were on average slightly shorter than other children, although the association only approached statistical significance. As this was an observational study, residual confounding cannot be excluded. Further studies are needed to confirm these associations, in particular those seen in certain sub-groups.


DNA hypermethylation of PTPN22 gene promoter in children and adolescents with Hashimoto thyroiditis.
Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is an inhibitor of T-cell activation, regulating intracellular signal transduction and thereby being implicated in the pathogenesis of autoimmune thyroid disease (AITD). The exact molecular mechanisms have not been fully elucidated. The aim of the present study was to quantitate DNA methylation within the PTPN22 gene promoter in children and adolescents with AITD and healthy controls. 60 Patients with Hashimoto thyroiditis (HT), 25 patients with HT and type 1 diabetes (HT + T1D), 9 patients with Graves' disease (GD) and 55 healthy controls without any individual or family history of autoimmune disease were enrolled. Whole blood DNA extraction, DNA modification using sodium bisulfate and quantification of DNA methylation in the PTPN22 gene promoter, based on melting curve analysis of the selected DNA fragment using a Real-Time PCR assay, were implemented. DNA methylation in the PTPN22 gene promoter was found to be significantly higher in HT patients (39.9 ± 3.1%) in comparison with other study groups (20.3 ± 2.4% for HT + T1D, 32.6 ± 7.8% for GD, 27.1 ± 2.4% for controls, p < 0.001). PTPN22 gene promoter DNA methylation was also associated marginally with thyroid autoimmunity in general (p = 0.059), as well as considerably with thyroid volume (p = 0.004) and the presence of goiter (p = 0.001) but not thyroid function tests. This study demonstrates for the first time that a relationship between autoimmune thyroiditis and PTPN22 gene promoter DNA methylation state is present, thus proposing another possible etiological association between thyroiditis and abnormalities of PTPN22 function. Further expression studies are required to confirm these findings.


Prediction of degree of residual stenosis in coronary thrombolysis.
In order to predict the residual stenosis in coronary thrombolysis, the factors easily obtained from clinical history--age, gender, history of angina before acute myocardial infarction (AMI), family history, hypertension, diabetes, hypercholesterolemia, smoking, and interval between onset of AMI and recanalization--were observed in 114 patients with successful coronary thrombolysis. In 55 patients with angina before AMI, 29 patients had residual stenosis greater than or equal to 75% and 26 patients had residual stenosis less than 75%. In 59 patients without angina before AMI, 15 patients had residual stenosis greater than or equal to 75%, and 44 patients had residual stenosis less than 75%. The presence or absence of angina before AMI was the main variable that discriminated the groups of residual stenosis of more or less than 75%, which was the only significant independent variable to predict the residual stenosis. These data suggest that the presence of angina pectoris before AMI is likely to be associated with a significant degree of residual stenosis after thrombolysis.


Surviving cancer treatment: an investigation of the experience of fear about, and monitoring for, recurrence in patients following treatment for colorectal cancer.
It is known that many individuals worry about their cancer recurring after colorectal cancer treatment but the significance and specific manifestations of this problem require exploration. This paper reports upon the research findings of a qualitative study to explain how fears of recurrence can affect individuals recovering from curative colorectal cancer surgery. A longitudinal, grounded theory study was conducted. Sixteen participants who had received curative treatment for colorectal cancer were interviewed on up to four occasions during the 12 months following their surgery, 62 interviews were conducted in total. Many participants expressed anxiety about if and when their cancer might return, despite the knowledge that they had had successful treatment for early-stage colorectal cancer. This fear led some to adopt new behaviours in a desire to achieve a more dependable and controllable body. Heightened monitoring and management of the body characterised a state of 'guarding' - a concept developed from the data. By contrast, other participants did not perceive the risk of cancer recurrence to be as personally threatening or were able to assume strategies to manage any such concerns and find a sense of resolution to their recovery. The nature of an individual's response to fears of recurrence and consequent impact on their recovery warrants greater clinical consideration. Providing opportunities to openly discuss the possibility of cancer recurrence, assessing individual fears and offering suggestions on possible coping strategies to lessen the associated distress, are essential supportive activities enabling transition to life beyond cancer.


Absence of lymphatic vessels in the developing human sclera.
The adult sclera is free of lymphatic vessels, but contains a net of blood vessels. Whether and when this selectively lymphangiogenic privilege is achieved during embryologic development is not known yet. Therefore, we investigated the developing human sclera for blood- and lymphatic vessels in 34 abortions/stillborns (12-38 weeks of gestation). The probes were subdivided into three groups (group 1: 12-18 weeks of gestation, n = 10; group 2: 19-23 weeks of gestation, n = 13; group 3: 24-38 weeks of gestation, n = 11), and prepared for paraffin sections followed by immunohistochemistry against CD31 to detect blood vessels, and against lymphatic vessel endothelial hyaluronan receptor-1 (LYVE1)/podoplanin to detect lymphatic vessels. We could show, that in the human episclera distinct CD31 + blood vessels are present as early as week of gestation 13. Their amount increased during pregnancy, whereas stromal CD31 + blood vessels were elevated in early pregnancy and regressed with ongoing pregnancy. In the lamina fusca CD31 + blood vessels were absent at any time point investigated. Single LYVE1 + cells were identified primarily in the episclera; their amount decreased significantly with increasing gestational ages (group 1 compared to group 3: p < 0.01). However, LYVE1+/podoplanin + lymphatic vessels were not detectable in the sclera at any gestational ages analyzed. In contrast to the conjunctiva where LYVE1+/podoplanin + lymphatic vessels were detectable as early as week 17, the amount of LYVE1 + cells in the sclera was highest in early pregnancy (group 1), with a significant decrease during continuing pregnancy (p < 0.001). These findings are the first evidence for a fetal lymphangiogenic privilege of the sclera and show, that the fetal human sclera contains CD31 + blood vessels, but is primarily alymphatic. Our findings suggest a strong expression of selectively antilymphangiogenic factors, making the developing sclera a potential model to discern antilymphangiogenic mechanisms.


Expanding applications of the 12-lead ECG in suspected acute infarction.
In the setting of acute myocardial infarction, the importance of the 12-lead electrocardiogram has increased tremendously. In addition to facilitating diagnosis of acute ischemic syndromes, including acute myocardial infarction, the 12-lead electrocardiogram may provide invaluable assistance in determining which patients are most suitable for thrombolytic therapy, and it may provide information that is useful in prognostic stratification.


Air permeability of compost as related to bulk density and volumetric air content.
Compost air permeability controls air flow through compost during composting or when using compost as biofilter material. Air permeability is therefore an important characteristic of compost. The relationships between air permeability (k(a)) in compost and compost dry bulk density (rho b), gravimetric water content (omega), and volumetric air content (epsilon) was investigated for two types of composts. The composts used were produced from a digested sewage sludge-straw mixture and from garden waste and measurements were conducted on sieved and repacked 100 cm3 compost samples. Results showed a linear relation between log(k(a)) and rho b at constant values of omega for both composts, indicating an exponential relationship between k(a) and rho b. The slopes of these relationships generally became more negative with increasing rho b. The results further showed a linear relationship between log(k(a)) and log(epsilon) for both composts as also often observed for soils. It was observed that the log(k(a)) and log(epsilon) relationships for the garden waste compost all intercepted at the same location despite having very different slopes. This means that it is possible to predict the entire k(a)-epsilon relationship using only one measurement of corresponding (k(a), epsilon) for garden waste. It was not possible to determine whether this was also the case for the sewage sludge compost due to difficulties in sample preparation at low and high water content.


Successful Management of Late Sinus Graft Infection via Functional Endoscopic Sinus Surgery and Press-Fit Block Bone Graft: A Case Report.
The purpose of this case report is to feature an interesting case where a staged approach was used to manage a failed implant site that led to a late sinus graft infection and sinusitis with an oroantral fistula (OAF), by using functional endoscopic sinus surgery (FESS) and an intraoral press-fit block bone graft technique. Sixteen years ago, a 60-year-old female patient underwent maxillary sinus augmentation (MSA) with 3 implants placed simultaneously in the right atrophic ridge. However, No. 3 and 4 implants were removed due to advanced peri-implantitis. The patient later developed purulent discharge from the site, headache, and complained of air leakage due to an OAF. The patient was referred to an otolaryngologist for FESS to treat the sinusitis. Two months after FESS, the sinus was re-entered. Residual inflammatory tissues and necrotic graft particles in the OAF site were removed. A block bone harvested from the maxillary tuberosity was press-fitted to the OAF site and grafted. After 4 months of grafting, the grafted bone was well incorporated with the surrounding native bone. Two implants were successfully placed in the grafted site with good initial stability. The prosthesis was delivered 6 months after implant placement. After the 2 years of follow-up, patient was functioning well without sinus complications. Within limitation of this case report, the staged approach via FESS and intraoral press-fit block bone graft is an effective method that can be used to successfully manage OAF and vertical defects at the implant site.


Fluorescence of native single-Trp mutants in the lactose permease from Escherichia coli: structural properties and evidence for a substrate-induced conformational change.
Six single-Trp mutants were engineered by individually reintroducing each of the native Trp residues into a functional lactose permease mutant devoid of Trp (Trp-less permease; Menezes ME, Roepe PD, Kaback HR, 1990, Proc Natl Acad Sci USA 87:1638-1642), and fluorescent properties were studied with respect to solvent accessibility, as well as alterations produced by ligand binding. The emission of Trp 33, Trp 78, Trp 171, and Trp 233 is strongly quenched by both acrylamide and iodide, whereas Trp 151 and Trp 10 display a decrease in fluorescence in the presence of acrylamide only and no quenching by iodide. Of the six single-Trp mutants, only Trp 33 exhibits a significant change in fluorescence (ca. 30% enhancement) in the presence of the substrate analog beta,D-galactopyranosyl 1-thio-beta,D-galactopyranoside (TDG). This effect was further characterized by site-directed fluorescent studies with purified single-Cys W33-->C permease labeled with 2-(4'-maleimidylanilino)-naphthalene-6-sulfonic acid (MIANS). Titration of the change in the fluorescence spectrum reveals a 30% enhancement accompanied with a 5-nm blue shift in the emission maximum, and single exponential behavior with an apparent KD of 71 microM. The effect of substrate binding on the rate of MIANS labeling of single-Cys 33 permease was measured in addition to iodide and acrylamide quenching of the MIANS-labeled protein. Complete blockade of labeling is observed in the presence of TDG, as well as a 30% decrease in accessibility to iodide with no change in acrylamide quenching. Overall, the findings are consistent with the proposal (Wu J, Frillingos S, Kaback HR, 1995a, Biochemistry 34:8257-8263) that ligand binding induces a conformational change at the C-terminus of helix I such that Pro 28 and Pro 31, which are on one face, become more accessible to solvent, whereas Trp 33, which is on the opposite face, becomes less accessible to the aqueous phase. The findings regarding accessibility to collisional quenchers are also consistent with the predicted topology of the six native Trp residues in the permease.


Time of day is an inaccurate surrogate marker for sleep-wake state in an epilepsy monitoring unit.
To assess the correlation between time of day and sleep-wake state prior to seizure onset for seizures recorded in an inpatient epilepsy monitoring unit. We prospectively enrolled a consecutive series of patients undergoing inpatient epilepsy monitoring. For each epileptic seizure recorded, continuous EEG data preceding seizure onset was reviewed and scored as W, N1-3, or REM in ten 30-second epochs. Time of day was divided into four 6-h phases (0600-1159, 1200-1759, 1800-2359, 0000-0559). The preictal sleep-wake state was then correlated to nocturnal (0000-0559) versus diurnal (0600-2359) times of day. A total of 102 seizures from 42 patients met enrollment criteria over a period of 19 months. Eighty-five seizures occurred during the diurnal phase, and 17 seizures occurred during the nocturnal phase. Thirty-six percent of all seizures (n = 37) were preceded by at least 1 epoch of sleep. The proportion of patients sleeping prior to a seizure within each 6-h phase varied significantly from the overall distribution only during nocturnal phase. Seventy-six percent of nocturnal seizures and 28 % of diurnal seizures were preceded by sleep. Therefore, the nocturnal time window from 0000-0559 had a sensitivity of 0.65 (95 % confidence interval 0.48-0.78), a specificity of 0.06 (0.02-0.15), a positive predictive value of 0.28 (0.20-0.39), and a negative predictive value of 0.24 (0.10-0.39) in association with sleep-onset seizures. The time of day is an inaccurate surrogate for preictal sleep-wake state in the epilepsy monitoring unit despite a correlation between nocturnal period and sleep. Diurnal sleep is a common phenomenon in the inpatient unit.


Preparation of chitosan nanofibers from completely deacetylated chitosan powder by a downsizing process.
Chitosan nanofibers were easily prepared from fully deacetylated chitosan dry powder using a high-pressure waterjet system. From SEM observation, after 10 cycles of treatment, most of the chitosan had been reduced to homogeneous nanofibers measuring tens of nanometers. On the other hand, further mechanical treatment did not show a significant change. Relative crystallinity of chitosan nanofibers gradually decreased as the number of passes increased since high-pressure waterjet treatment damaged the crystalline region of chitosan nanofibers. The transmittance of the chitosan nanofiber slurry increased steeply, as the number of passes increased, indicating that the chitosan fibers were disintegrated effectively. Viscosity of chitosan nanofiber slurry also showed that the chitosan disintegrated well into nanofibers up to 10 passes. Above 10 passes, disintegration efficiency was saturated. The molecular weights of the nanofibers steeply decreased due to the depolymerization of chitosan by mechanical disintegration. The Young's modulus and tensile strength of chitosan nanofiber sheets were improved as the number of treatments increased, but further treatments deteriorated the tensile strength.


Aromatic-aromatic interactions and protein stability. Investigation by double-mutant cycles.
The side-chains of phenylalanine and tyrosine residues in proteins are frequently found to be involved in pairwise interactions. These occur both within repeating elements of secondary structure and in tertiary and quaternary interactions. It has been suggested that they are important in protein folding and stability, and non-bonded potential energy calculations indicate that a typical aromatic-aromatic interaction has an energy of between -1 and -2 kcal/mol and contributes between -0.6 and -1.3 kcal/mol to protein stability. There is such an aromatic pair on the solvent-exposed face of the first alpha-helix of barnase, the small ribonuclease from Bacillus amyloliquefaciens. The edge of the aromatic ring of Tyr17 interacts with the face of that of Tyr13. The two residues have been mutated both singly and pairwise to alanine, and their free energies of unfolding determined by denaturation with urea. Application of the double-mutant cycle analysis gives an interaction energy of -1.3 kcal/mol for the aromatic pair in the folded protein relative to solvation by water in the unfolded protein. This value is similar to that calculated from the change in surface-accessible area between the rings on the formation of the pair. Analysis of a further double-mutant cycle in which the Tyr residues are mutated to Phe indicates that the aromatic-aromatic interactions of Tyr/Tyr and Phe/Phe make identical contributions to protein stability. However, Tyr is preferred to Phe by 0.3(+/- 0.04) kcal/mol at the solvent-exposed face of the alpha-helix.


Gastroenteritis in Men Who Have Sex With Men in Seattle, Washington, 2017-2018.
Men who have sex with men (MSM) are at risk for sexual transmission of enteric pathogens. The microbiology of gastroenteritis in MSM has not been examined since the advent of antiretroviral therapy and molecular diagnostics. Our objective was to assess the causes of gastroenteritis among MSM living with and without human immunodeficiency virus (HIV) coinfection in Seattle, Washington. We conducted a retrospective cohort study of 235 MSM who underwent multiplex stool polymerase chain reaction (PCR) testing between 1 January 2017 and 1 June 2018. We abstracted clinical and laboratory data from electronic medical records. Parallel or reflexive culture and susceptibility testing were performed when PCR detected cultivable pathogens. Among 235 MSM tested (268 episodes), 131 had 151 episodes with positive test results. 148 (63.0%) individuals were living with HIV. Among positive tests, 88.7% detected a bacterial pathogen, 26% a virus, and 40% a parasite. Diarrheagenic Escherichia coli (enteroaggretative, enteropathogenic), Shigella, and Campylobacter were the most commonly detected bacteria (33.1%, 30.5%, and 17.2% of positive samples, respectively). Forty-three percent of positive specimens had ≥2 pathogens. Etiologies and clinical presentations were similar between men living with and without HIV. Cultured Shigella and Campylobacter isolates were frequently resistant to multiple antibiotics. MSM present with gastroenteritis from varied pathogens, including some not detected by conventional stool culture. High levels of antibiotic resistance are consistent with frequent antibiotic exposure in this population and the transmission of multiresistant strains. New approaches are needed to detect, treat, and prevent enteric infections in MSM.


An inexpensive optical probe for measuring the local specific interfacial area.
An in situ optical probe was developed to measure reliably the local specific interfacial area of the suspended phase (specifically air bubbles) in a bioreactor. The light transmission-based probe can be simply and inexpensively constructed from readily available components. The probe's performance was tested in a suspension of opaque monodisperse polystyrene spheres as well as in the presence of nonspherical, nonuniformly distributed bubbles. The probe signal is directly related to the local specific interfacial area by a calibration equation obtained with polystyrene beads, as opposed to the cumbersome direct photographic bubble measurements that the probe attempts to replace. Its utility was demonstrated by measuring the specific bubble interfacial area at two locations in a bioreactor at various agitation intensities.


Characterization of cryoprecipitates in pemphigus: demonstration of pemphigus antibody activity in cryoprecipitates using the immunofluorescent technique.
Cryoproteins observed in patients with pemphigus have been shown to contain IgG, complement components, and other serum proteins. The IgG moiety possessed pemphigus antibody activity and contained kappa and lambda light chains. Cryoproteins appeared in the clinically active stage and disappeared subsequent to clinical improvement. These observations indicate that immune complexes may exist in the sera of patients with pemphigus.


Lacticaseibacillus rhamnosus GR-1, a.k.a. Lactobacillus rhamnosus GR-1: Past and Future Perspectives.
Lacticaseibacillus rhamnosus GR-1 (LGR-1) (previously classified as Lactobacillus rhamnosus GR-1) is the most researched probiotic strain for women's health. Its various urogenital health effects, including a reduction in the recurrence of bacterial vaginosis and urinary-tract infection, are well documented. The strain has also been safely used by HIV-positive subjects, a portion of whom have reported reduced diarrhea and increased CD4 counts. Unlike most probiotic strains used for urogenital health, LGR-1 has been extensively studied for its properties, including its genomic and metabolic traits and its surface properties. This review aims to highlight the totality of research performed with LGR-1, to act as a rigorous scientific benchmark for probiotic microbes, especially for application to women's health.


Missed opportunities for pregnancy prevention among insured adolescents.
Birth to a teenaged mother is associated with adverse health and social outcomes. Adolescents at risk for pregnancy may not receive needed reproductive health services at primary care visits. To review services provided at outpatient visits in the year prior to pregnancy among adolescents in a US Midwestern integrated health care delivery system. Retrospective medical record review of continuously insured adolescents aged 15 to 19 years experiencing pregnancy in a nonprofit Minnesota health care organization. Primary care visits in the year prior to pregnancy. Adolescents experiencing a pregnancy with stable insurance coverage had an estimated average of 2.7 primary care visits in the 12 months prior to becoming pregnant. Medical record review revealed that 57% did not have documentation of sexual activity and 47% did not have documentation of reproductive health counseling. These rates varied by health care professional type and visit type. Only 35% had contraception prescribed within 12 months of becoming pregnant and only 1 had a long-acting contraceptive prescribed. Our data highlight the need for primary care professionals to review health behaviors and pregnancy risk at all adolescent encounters.