HLA-B*13, B*35 and B*39 Alleles Are Closely Associated With the Lack of Response to ART in HIV Infection: A Cohort Study in a Population of Northern Brazil.
Immune reconstitution failure after HIV treatment is a multifactorial phenomenon that may also be associated with a single polymorphism of human leukocyte antigen (HLA); however, few reports include patients from the Brazilian Amazon. Our objective was to evaluate the association of the immunogenic profile of the "classical" HLA-I and HLA-II loci with treatment nonresponse in a regional cohort monitored over 24 months since HIV diagnosis. Treatment-free participants from reference centers in the state of Pará, Brazil, were enrolled. Infection screening was performed using enzyme immunoassays (Murex AG/AB Combination DiaSorin, UK) and confirmed by immunoblots (Bio-Manguinhos, FIOCRUZ). Plasma viral load was quantified by real-time PCR (ABBOTT, Chicago, Illinois, USA). CD4+/CD8+ T lymphocyte quantification was performed by immunophenotyping and flow cytometry (BD Biosciences, San Jose, CA, USA). Infection was monitored via test and logistics platforms (SISCEL and SICLOM). Therapeutic response failure was inferred based on CD4+ T lymphocyte quantification after 1 year of therapy. Loci A, B and DRB1 were genotyped using PCR-SSO (One Lambda Inc., Canoga Park, CA, USA). Statistical tests were applied using GENEPOP, GraphPad Prism 8.4.3 and BioEstat 5.3. Of the 270 patients monitored, 134 responded to treatment (CD4+ ≥ 500 cells/µL), and 136 did not respond to treatment (CD4+ < 500 cells/µL). The allele frequencies of the loci were similar to heterogeneous populations. The allelic profile of locus B was statistically associated with treatment nonresponse, and the B*13, B*35 and B*39 alleles had the greatest probabilistic influence. The B*13 allele had the highest risk of treatment nonresponse, and carriers of the allele had a detectable viral load and a CD4+ T lymphocyte count less than 400 cells/µL with up to 2 years of therapy. The B*13 allele was associated with a switch in treatment regimens, preferably to efavirenz (EFZ)-based regimens, and among those who switched regimens, half had a history of coinfection with tuberculosis. The allelic variants of the B locus are more associated with non-response to therapy in people living with HIV (PLHIV) from a heterogeneous population in the Brazilian Amazon.


[Diabetes mellitus: an epidemic rise?].
Diabetes mellitus is becoming an increasingly important issue in insurance medicine. Given the rising numbers of overweight applicants, an important question is wether the number of diabetic applicants is also rising, and if so, by how much. The media talks of an epidemic of obese poeple. Is the same true of diabetes mellitus? And what can wo do? Higher loadings? Nothings? Let us take a closer look at the prevalence and incidence rates. Hopefully, this will shed some light on this problem.


[Production and absorption rate of cerebrospinal fluid in the spinal subarachnoid space of the dog (author's transl)].
Adult mongrel dogs, weighing 10-17 kg. were anesthetized with Nembutal and cervical and lumbosacral laminectomy was performed. The spinal subarachnoid space was blocked by extradural ligation at the level of the C4 to interrupt CSF communication between the cranial and spinal space. Polyethylene catheters were placed in the cervical and lumbosacral subarachnoid space, and artificial Mock CSF buffer, pH 7.35-7.40, containing inulin of 25 mg/dl or 14C-inulin of 1.5-2 muCi/dl as a tracer was perfused in the sacro-cervical direction through the catheter. After a steady state of perfusion was acommplished, the CSF was collected from the outlet catheter. Production and absorption rate of the CSF were calculated after Pappenheimer and Heisey's equation. 1) Effects of CSF pressure on the rate of production (Vf) and absorption (Va) of CSF and on the difference between outflow fluid rate (Vo) and inflow fluid rate (Vi) were studied within the pressure range of -100 to +600 mmH2O. Then, regression lines were calculated by means of the least square method. See Article. Vf was little affected by changes in CSF pressure, while Va increased linearly as CSF pressure elevated. This suggests that the spinal subarachnoid space plays an important role as a site of CSF absorption when the intracranial pressure increases. Vo-Vi, that is difference between absorption and production rate, decreased linearly as the CSF pressure increased. 2) Under a constant CSF pressure of +200 mmH2O, the effects of glucocorticoids (dexamethasone, 0.25 mg/kg and hydrocortisone, 4.15 mg/kg) and a carbonic anhydrase inhibitor (acetazolamide, 10 mg/kg) upon the production and absorption rate of CSF were determined 1/2, 1, 2 and 3 hours after intravenous administration. a) Effect of dexamethasone: The rate of CSF production was reduced to 60.5 +/- 2.4% (p less than 0.001) of the control level. The absorption rate of CSF also decreased to 59.2 +/- 6.09% (p less than 0.001) of the control. b) Effect of hydrocortisone: The production rate of CSF decreased to 67.4 +/- 6.61% (p less than 0.001), and the absorption rate to 76.5 +/- 3.94% (p less than 0.001) of the control level. c) Effect of acetazolamide: The production and absorption rate also decreased to 57.2 +/- 5.61% (p less than 0.001) and to 56.9 +/- 7.02% (p less than 0.001), respectively. 3) Pentration of tritiated dexamethasone and tritiated hydrocortisone from plasma to CSF. The penetration of tritiated dexamethasone and tritiated hydrocortisone from plasma to CSF in the spinal and cranial subarachnoid space was observed after the intravenous administration. The CSF/Plasma ratio of dexamethasone was 30.9% at 15 minutes and gradually increased to 91.5% and 93.5%, respectively, in the cranial and spinal CSF at 3 hours after the injection.


[Therapy of venous leg ulcer].
The socio-medical importance of venous leg ulcers is clear, considering that 2% of adults are suffering from. Hospitalization-time is twice as long than the average. The ratio female: male is about 2-3:1. 90% are venous leg ulcers. There is agreement to treat venous leg ulcers by compressive dressings basically. External local therapy can optimize the wound-healing. Contact dermatitis in about 80% of patients demand the use of 'inert' dressings, i.e. polyurethane foam dressings (e.g. Lyomousse).


Direct Adsorption of Anti-CD34 Antibodies on the Nano-Porous Stent Surface to Enhance Endothelialization.
In-stent restenosis following the insertion of conventional drug-eluting stent has become an extremely serious problem due to coating techniques, with polymer matrices used to bind biological ingredients to the stent surface. However, several studies have indicated that new pro-healing technique could prevent stent thrombosis that can be caused by conventional drug-eluting stents. A novel method of attaching anti-CD34 antibodies directly on the porous surface of a 316L stainless steel bare metal stent was developed in this study, which achieved both high stability of attached anti-CD34 antibodies on the metal stent surface and high antibody activity for stem cell capture. The in vitro and in vivo experimental results indicated that the new stent with directly coupled anti-CD34 antibodies can efficiently enhance stent endothelialization. This study indicates that we have developed a unique method of attaching anti-CD34 antibodies directly on the porous surface of a 316L stainless steel bare metal stent, which provides a novel polymer-free approach for developing pro-healing stents.


Clinicopathologic considerations of fusobacteria chorioamnionitis.
When sought by light microscopy in formalin-fixed tissue, fusobacteria are apparent in 7-18% of chorioamnionitis cases. Brown and Hopps bacterial staining characteristically visualizes their long, slender and filamentous forms. Fusobacteria-like organisms in placentae have previously been associated with prematurity. Our findings indicate that perinatal infection with fusobacteria may cause neonatal death from prematurity, rather than from sepsis. In a study of 586 placentae, 14 specimens with chorioamnionitis and fusobacteria-like organisms were found. On the five occasions when microbiologic tests were made, fusobacteria were isolated. Prematurity of the newborns was associated with twelve of those placentae. Immunofluorescent labelling of the organisms is a helpful but incomplete means of diagnosis. Because fusobacteria antibodies are highly specific, they do not cross-react with other members of the genus Fusobacterium. A typical case is reported, in detail.


Clinical efficacy of acetylcysteine combined with tetrandrine tablets in the treatment of silicosis and the effect on serum IL-6 and TNF-α.
Clinical efficacy of acetylcysteine combined with tetrandrine tablets in the treatment of silicosis and the effect on serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in patients with silicosis was investigated. One hundred and ninety-six patients with silicosis admitted to Qingdao Central Hospital, aged 40 to 70 years, were collected by prospective analysis. The patients were divided into two groups according to the different methods of treatment. The 108 patients in the control group received routine treatment, including anti-inflammatory, cough and asthma relief and 88 patients in the observation group were treated with tetrandrine combined with N-acetylcysteine on the basis of routine treatment. The curative effect of the two groups was analyzed by X-ray, and the incidence of adverse reactions was compared between the two groups. There was no significant difference in the effective rate between the two groups (P>0.05). After treatment, respiratory rate (RR) decreased, and forced vital capacity (FVC), and first second forced expiratory volume (FEV1) increased in both groups (P<0.05). RR in the observation group was lower than that in the control group (P<0.05), FVC and FEV1 were higher than those in the control group (P<0.05). There was no significant difference in serum IL-6 and TNF-α levels between the two groups before treatment (P>0.05). After treatment, the levels of IL-6 and TNF-α in the two groups decreased (P<0.05), and the IL-6 and TNF-α levels in the observation group after treatment were significantly lower than those in the control group (P<0.05). According to the effect of clinical treatment, the patients were re-divided into two groups. In conclusion, tetrandrine combined with acetylcysteine can effectively improve the clinical therapeutic effect of silicosis and alleviate the degree of inflammatory reaction in patients with silicosis. The levels of IL-6 and TNF-α in peripheral blood are valuable for the clinical treatment of silicosis.


An uncommon, life-threatening, traumatic hematoma in the neck area.
It is well known that blunt neck trauma, when compared to a penetrating injury in the same anatomical area, is very rare. We report a case of an 81-year-old Caucasian woman with a blunt life-threatening neck trauma due to a bully goat. Although rare, direct evaluation should always be done in these cases because any misinterpretation may result in unfavorable outcomes. We have to highlight that close medical attention and prompt surgical treatment should be always considered in order to avoid dramatic consequences.


Third-body abrasive wear of tibial polyethylene inserts combined with metallic and ceramic femoral components in a knee simulator study.
Total knee arthroplasties have reached a high grade of quality and safety, but most often fail because of aseptic implant loosening caused by polyethylene wear debris. Wear is generated at the articulating surfaces, e.g. caused by third-body particles. The objective of this experimental study was to determine the wear of tibial polyethylene inserts combined with metallic and ceramic femoral components under third-body wear conditions initiated by bone cement particles. Wear testing using a cemented unconstrained bicondylar knee endoprosthesis (Multigen Plus CR knee system) was performed in a knee wear simulator. Tibial polyethylene inserts were combined with the identical femoral component design, but made of two different materials (cobalt-chromium and ceramic). Bone cement debris including zirconium oxide particles was added every 500,000 cycles between the articulating surfaces. After 5 million load cycles, the amount of wear was determined gravimetrically and compared with results from standard wear test conditions. The surfaces of tibial inserts were also analyzed. The average gravimetrical wear of the tibial polyethylene inserts in combination with cobalt-chromium and ceramic femoral components under third-body wear conditions amounted to 31.88 ± 4.53 mg and 13.06 ± 1.88 mg after 5 million cycles, respectively, and was higher than under standard wear test conditions in both cases. The wear simulator test demonstrates that wear of polyethylene inserts under third-body wear conditions, in combination with ceramic femoral components, was significantly lower than with metallic femoral components.


The effect of cryoprotection on the use of PLGA encapsulated iron oxide nanoparticles for magnetic cell labeling.
Magnetic PLGA nanoparticles are a significant advancement in the quest to translate MRI-based cell tracking to the clinic. The benefits of these types of particles are that they encapsulate large amounts of iron oxide nanocrystals within an FDA-approved polymer matrix, combining the best aspects of inert micron-sized iron oxide particles, or MPIOs, and biodegradable small particles of iron oxide, or SPIOs. Practically, PLGA nanoparticle fabrication and storage requires some form of cryoprotectant to both protect the particle during freeze drying and to promote resuspension. While this is a commonly employed procedure in the fabrication of drug loaded PLGA nanoparticles, it has yet to be investigated for magnetic particles and what effect this might have on internalization of magnetic particles. As such, in this study, magnetic PLGA nanoparticles were fabricated with various concentrations of two common cryoprotectants, dextrose and sucrose, and analyzed for their ability to magnetically label cells. It was found that cryoprotection with either sugar significantly enhanced the ability to resuspend nanoparticles without aggregation. Magnetic cell labeling was impacted by sugar concentration, with higher sugar concentrations used during freeze drying more significantly reducing magnetic cell labeling than lower concentrations. These studies suggest that cryoprotection with 1% dextrose is an optimal compromise that preserves monodispersity following resuspension and high magnetic cell labeling.


Voluntary sustainability standards could significantly reduce detrimental impacts of global agriculture.
Voluntary sustainability standards (VSS) are stakeholder-derived principles with measurable and enforceable criteria to promote sustainable production outcomes. While institutional commitments to use VSS to meet sustainable procurement policies have grown rapidly over the past decade, we still have relatively little understanding of the (i) direct environmental benefits of large-scale VSS adoption; (ii) potential perverse indirect impacts of adoption; and (iii) implementation pathways. Here, we illustrate and address these knowledge gaps using an ecosystem service modeling and scenario analysis of Bonsucro, the leading VSS for sugarcane. We find that global compliance with the Bonsucro environmental standards would reduce current sugarcane production area (-24%), net tonnage (-11%), irrigation water use (-65%), nutrient loading (-34%), and greenhouse gas emissions from cultivation (-51%). Under a scenario of doubled global sugarcane production, Bonsucro adoption would further limit water use and greenhouse gas emissions by preventing sugarcane expansion into water-stressed and high-carbon stock ecosystems. This outcome was achieved via expansion largely on existing agricultural lands. However, displacement of other crops could drive detrimental impacts from indirect land use. We find that over half of the potential direct environmental benefits of Bonsucro standards under the doubling scenario could be achieved by targeting adoption in just 10% of global sugarcane production areas. However, designing policy that generates the most environmentally beneficial Bonsucro adoption pathway requires a better understanding of the economic and social costs of VSS adoption. Finally, we suggest research directions to advance sustainable consumption and production.


Psychiatric co-morbidity and substance use disorders: treatment in parallel systems or in one integrated system?
Psychiatric co-morbidity among substance users refers to the simultaneous presence of at least another psychiatric disorder in a person diagnosed with a substance use disorder. Co-morbid patients represent a substantial number of people in treatment and present greater disorder severity from both the clinical and social perspectives than those people diagnosed with only one type of disorder. We present an overview of the current state of the art concerning the choice of site of treatment, the kind of intervention, the length of such treatment, and future goals, aiming to establish a more effective intervention, and finally so as to further improve clinical outcomes.


Synthesis and Application of Amine Functionalized Iron Oxide Nanoparticles on Menaquinone-7 Fermentation: A Step towards Process Intensification.
Industrial production of menaquione-7 by Bacillus subtilis natto is associated with major drawbacks. To address the current challenges in menaquione-7 fermentation, studying the effect of magnetic nanoparticles on the bacterial cells can open up a new domain for intensified menqainone-7 process. This article introduces the new concept of production and application of l-lysine coated iron oxide nanoparticles (l-Lys@IONs) as a novel tool for menaquinone-7 biosynthesis. l-Lys@IONs with the average size of 7 nm were successfully fabricated and were examined in a fermentation process of l-Lys@IONs decorated Bacillus subtilis natto. Based on the results, higher menaquinone-7 specific yield was observed for l-Lys@IONs decorated bacterial cells as compared to untreated bacteria. In addition, more than 92% removal efficacy was achieved by using integrated magnetic separation process. The present study demonstrates that l-Lys@IONs can be successfully applied during a fermentation of menaquinone-7 without any negative consequences on the culture conditions. This study provides a novel biotechnological application for IONs and their future role in bioprocess intensification.


N- and L-type calcium channel antagonist improves glomerular dynamics, reverses severe nephrosclerosis, and inhibits apoptosis and proliferation in an l-NAME/SHR model.
To determine the responses of the new dihydropyridine N- and L-type calcium antagonist, cilnidipine, on systemic and renal hemodynamics, glomerular dynamics, renal function, and histopathology in an Nomega-nitro-l-arginine methylester spontaneously hypertensive rat (l-NAME/SHR) model of nephrosclerosis. Five groups of 20-week-old male SHR were studied using renal micropuncture techniques and histopathological analyses: group 1, control; group 2, cilnidipine (10 mg/kg per day) by gavage, for 3 weeks; group 3, l-NAME (50 mg/l) in drinking water, for 3 weeks; group 4, combination of l-NAME and cilnidipine, for 3 weeks; group 5, l-NAME for 3 weeks, followed by cilnidipine for a subsequent 3 weeks. Cilnidipine significantly reduced mean arterial pressure, total peripheral resistance and renal vascular resistance, while increasing effective renal blood flow and glomerular filtration rate (P < 0.01) in l-NAME/SHR. These hemodynamic changes were associated with significantly increased single nephron glomerular filtration rate (SNGFR) and plasma flow (SNPF) and decreased afferent glomerular arteriolar resistances when cilnidipine was used alone, and with increased SNGFR and SNPF, but decreased glomerular capillary pressure, afferent and efferent arteriolar resistances, urinary protein excretion, serum creatinine and uric acid concentrations (at least P < 0.05) in l-NAME-exacerbated SHR nephrosclerosis. In addition, glomerular and arteriolar injuries were markedly reversed (both P < 0.01), and glomerular apoptosis and cellular proliferation were inhibited and associated with glomerular tuft enlargement and an increase in cell number. Cilnidipine not only prevented, but reversed, the severe renal hemodynamic and glomerular dynamic changes, including apoptosis and glomerular cellular proliferation, in l-NAME/SHR-exacerbated nephrosclerosis. This dual-channel calcium antagonist thus exerted renoprotective pathophysiological effects in the l-NAME/SHR.


Binding and uptake of [3H]adrenaline by perfused rat liver.
The binding and uptake of [3H]adrenaline by the intact perfused rat liver was investigated. We showed that the administration of [3H]adrenaline to liver resulted in the rapid uptake of the radioligand, and that such uptake was independent of any Ca2+ redistributions induced by the hormone. At low adrenaline concentrations (less than 50 nM) uptake was inhibited by prazosin, whereas at higher hormone concentrations a significant proportion of total [3H]adrenaline uptake could not be inhibited by this antagonist. [3H]Adrenaline uptake could be directly correlated with adrenaline-induced responses such as an increased rate of respiration and glycogenolysis. The partial inhibition (approx. 25%) of [3H]adrenaline uptake by antagonists was sufficient for the total inhibition of hormone-induced responses. The effect of various pharmacological agents on [3H]adrenaline uptake was investigated, and the contribution of tissue-related factors to alpha-adrenergic agonist-antagonist interactions in vivo is discussed.


[An early phase II clinical study of RP56976 (docetaxel) in patients with cancer of the gastrointestinal tract].
An early phase II clinical study of RP56976 (docetaxel), a new semisynthetic agent, was conducted in patients with apparatus digestorius cancer. Two or more intravenous doses of 60 mg/m2 were administered with dose-free intervals of 3-4 weeks. Of the 44 patients enrolled, 32 patients (15 patients with gastric cancer, 16 patients with colon cancer, and 1 patient with pancreatic cancer) completed the scheduled course of treatment. For antitumor efficacy in the 15 patients with gastric cancer that completed the study, 3 showed a partial response (PR)(20.0%). Of the 16 patients with colon cancer that completed the study, 1 showed a partial response (PR)(6.3%). No efficacy was noted in the patient with pancreatic cancer. All three patients with gastric cancer showing a partial response (PR) to docetaxel had displayed no response to previous chemotherapy. Evaluation was made for the primary gastric lesion and metastatic lesions in cervical lymph nodes and liver. The most frequent adverse reactions included leukopenia (100%) and neutropenia (97.2%) and subjective/objective adverse reactions included alopecia (80.6%), anorexia (72.2%), fatigue (52.8%), fever (47.2%) nausea/vomiting (47.2%), and diarrhea (38.9%). Leukopenia was of Grade III or more in 75.0% of the patients and neutropenia was of Grade III or more in 91.7%. All other adverse reactions were acceptable. The results suggest that docetaxel is an effective anticancer agent for gastric cancer.


Destructive pseudo-neuroarthropathy associated with calcium pyrophosphate deposition.
Calcium pyrophosphate deposition (CPPD) disease is a metabolic disorder characterized by soft tissue calcific deposits formed primarily in articular cartilage. What can result is a crystal-induced arthropathy often referred to as pseudogout, which is variable in both presentation and severity. A particularly destructive and deforming arthritis is an uncommon but well-recognized subtype of this disease. Radiologically resembling the neuroarthropathy described by Charcot, a pattern of joint fragmentation and structural collapse occurs in the absence of peripheral neuropathy. This pseudo-neuroarthropathy is rarely reported in the foot and ankle. A total of 15 cases of pseudo-neuroarthropathy involving some previously unreported joints within the foot and ankle are described in this case series of 9 patients. All patients presented with disease involving multiple joints. Clinical deformity was apparent in each case, and extensive joint destruction was seen on plain radiographs. In 6 patients, histopathological CPPD disease was confirmed on tissue biopsy of the affected joints. In the remaining 3 patients a clinical diagnosis was made on the basis of the classic appearance of pseudo-neuroarthropathy in the foot, with additional recognized features of CPPD. Operative management with deformity correction using joint arthrodesis produced satisfactory clinical and radiological results. In the absence of peripheral neuropathy and systemic disease, the pseudo-neuroarthropathy of CPPD should be considered when a progressively deforming and destructive arthritis is seen in the foot and ankle. Level IV, case series.


Formation of kinetically trapped small clusters of PEGylated gold nanoparticles revealed by the combination of small-angle X-ray scattering and visible light spectroscopy.
Gold nanoparticles coated with polyethylene glycol (PEG) are able to form clusters due to the collapse of the surface-grafted polymer chains when the temperature and ion concentration of the aqueous medium are increased. The chain collapse reduces the steric repulsion, leading to particle aggregation. In this work, we combine small angle X-ray scattering (SAXS) and visible light spectroscopy to elucidate the structure of the developing clusters. The structure derived from the SAXS measurements reveals a decrease in interparticle distance and drastic narrowing of its distribution in the cluster, indicating restricted particle mobility and displacement within the cluster. Surprisingly, instead of forming a large crystalline phase, the evolving clusters are composed of about a dozen particles. The experimental optical extinction spectra measured during cluster formation can be very well reproduced by optical simulations based on the SAXS-derived structural data.


Everyday ethics in an acute psychiatric unit.
The paper begins with a brief statement about the centrality of autonomy or self governance as a core ethical value in the interaction between health care worker and patient. Then there are three stories describing everyday interactions in an acute psychiatric unit. These are used to help unravel ethical issues relating to patient autonomy. Each story is analysed for its ethical components by describing the protagonists' different perspectives, and their reactions to the events. Attention is also paid to institutional policy. Suggestions are made for small changes in both staff behaviour and institutional procedures. Such changes could enhance rather than diminish patient autonomy.


[Guidelines for the treatment on infections caused by methicillin-resistant Staphylococcus aureus].
Infections due to methicillin-resistant Staphylococcus aureus (MRSA) have undergone important changes in the last five years that have influenced the choice of therapy: i) increase of their frequency in hospital-associated settings and, more recently, in community settings; ii) better knowledge of clinical implications of the pharmacokinetic and pharmacodynamic properties of vancomycin; iii) improvement of current standard methods for rapid detection of MRSA in clinical samples; iv) clear evidence that vancomycin is losing efficacy against MRSA with MIC > 1 microg/mL; and v) appearance of new antibiotics suitable for use in these infections (linezolid, daptomycin, tigecyclin). Under this situation guidelines for the treatment of common infections caused by MRSA appear to be necessary to improve the efficacy and reduce the mortality.


Pediatric update #4. Familial congenital short femur: intrauterine detection and follow-up by ultrasound. A case report.
A case of familial congenital simple short femur is described in an 8-year-old brother and an 8-month-old sister, associated with other congenital defects in the lower extremities. In the case of the sister, early intrauterine detection and follow-up were possible. This early intrauterine detection by means of ultrasound may enable us to calculate the ratio between the length of the short femur and that of the normal one and to plan for corrective surgery at a later date.


TCMIO: A Comprehensive Database of Traditional Chinese Medicine on Immuno-Oncology.
Advances in immuno-oncology (IO) are making immunotherapy a powerful tool for cancer treatment. With the discovery of an increasing number of IO targets, many herbs or ingredients from traditional Chinese medicine (TCM) have shown immunomodulatory function and antitumor effects via targeting the immune system. However, knowledge of underlying mechanisms is limited due to the complexity of TCM, which has multiple ingredients acting on multiple targets. To address this issue, we present TCMIO, a comprehensive database of Traditional Chinese Medicine on Immuno-Oncology, which can be used to explore the molecular mechanisms of TCM in modulating the cancer immune microenvironment. Over 120,000 small molecules against 400 IO targets were extracted from public databases and the literature. These ligands were further mapped to the chemical ingredients of TCM to identify herbs that interact with the IO targets. Furthermore, we applied a network inference-based approach to identify the potential IO targets of natural products in TCM. All of these data, along with cheminformatics and bioinformatics tools, were integrated into the publicly accessible database. Chemical structure mining tools are provided to explore the chemical ingredients and ligands against IO targets. Herb-ingredient-target networks can be generated online, and pathway enrichment analysis for TCM or prescription is available. This database is functional for chemical ingredient structure mining and network analysis for TCM. We believe that this database provides a comprehensive resource for further research on the exploration of the mechanisms of TCM in cancer immunity and TCM-inspired identification of novel drug leads for cancer immunotherapy. TCMIO can be publicly accessed at http://tcmio.xielab.net.


[Quantitative structure-activity relationship prediction of carcinogenicity of N-nitroso compounds based on category approach and read-across].
Objective: New quantitative structure-activity relationship (QSAR) method was used to predict N-nitroso compounds (NOCs) carcinogenicity. This could provide evidences for health risk assessment of the chemicals. Methods: Total 74 chemical substances of NOCs were included as target chemicals for this validation study by using QSAR Toolbox based on category approach and read-across. The included 74 NOCs were categorized and subcategorized respectively using "Organic functional groups, Norbert Haider " profiler and "DNA binding by OASIS V.1.1" profiler. Carcinogenicity of rat were used as target of prediction, the carcinogenicity results: of analogues in chemical categories were cross-read to obtain the carcinogenic predictive results of the target chemicals. Results 74 NOCs included 26 nonclic N-nitrosamines, 24 cyclic N-nitrosamines and 24 N-nitrosamides The sensitivity, specificity and concordance of the category approach and read-across for predicting carcinogenicity of 74 NOCs were 75% (48/64), 70%(7/10) and 74% (55/74) respectively. The concordance for noncyclic N-nitrosamines, cyclic N-nitrosamines and N-nitrosamides were 88% (23/26), 71% (17/24) and 63% (15/24) respectively. Conclusion: QSAR based on category approach and read-across is good for prediction of NOCs carcinogenicity, and can be used for high-throughput qualitative prediction of NOCs carcinogenicity.


Suicidal Ideation, Depressive Symptomatology, and Self-Concept: A Comparison Between Mexican Institutionalized and Noninstitutionalized Children.
Previous research reports a significant prevalence of child depression worldwide and self-concept as a predictor of depression and suicide behavior. Although suicide in children is an increasing problem in Mexico, there are scarce studies reporting risk factors and none of children in foster care institutions. This was a comparative, ex post facto study whose aim was to analyze associations between suicidal ideation, depression, and self-concept in two paired samples of Mexican children (83 institutionalized and 83 noninstitutionalized). Results show 16% of the children reported suicidal ideation and statistically significant differences among variables in both samples. Suggestions are made to address this problem from early ages.


Complexation of high methoxyl pectin with ethanol desolvated whey protein nanoparticles: physico-chemical properties and encapsulation behaviour.
Using a desolvation method, whey protein isolate (WPI) nanoparticles were prepared and mixed with high methoxyl pectin (HMP) solutions (DE 72.8) to form WPI-HMP supramolecular complexes at low pH. Aqueous dispersions containing 5% WPI at pH 9 were desolvated with ethanol, and then diluted in HMP solutions at pH 3. Changes in particle size of the HMP-WPI complexes were studied as a function of HMP concentration. Upon dilution of the WPI nanoparticles in 0.05% HMP at pH 3, the average apparent diameter (d(90)) was around 270 nm, and there were no differences with desolvation level. These nanoparticles would undergo coarsening with storage at room temperature. The complexes showed to withstand homogenization and although heating increased aggregation, the particle size of the heated suspensions improved after homogenization. In addition, the suspensions demonstrated higher interfacial pressures (measured by drop tensiometry) compared to the corresponding unprocessed, desolvated or heated WPI solutions, suggesting their employment as surface active ingredients. The encapsulation efficiency of the desolvated WPI suspensions and desolvated WPI-HMP complex suspensions was studied using a model hydrophilic dye. In all cases, appreciable amounts of dye molecule were encapsulated and retained by the nanoparticles during storage at pH 3.


In situ observation of water in a fuel cell catalyst using scanning electron microscopy.
To visualize water in the catalyst of polymer electrolyte fuel cells (PEFCs), backscattered electron (BSE) imaging by means of scanning electron microscopy was employed. To confine a wet specimen of catalyst, an environmental wet cell was manufactured with a silicon nitride thin film (∼100 nm) as the beam window. By supplying humidified gas into the cell, a change in BSE brightness was detected in the catalyst attached to the silicon nitride window. As humidification proceeded, the BSE image became darker and returned brighter by switching to a dry gas. Monte Carlo simulations were performed to evaluate the energy and number of BSE obtained after passing through water with thickness d. Combining the results of the Monte Carlo simulation successfully converted the change in brightness to the change in thickness from d = 100 nm to d = 3 μm. This established method of evaluating water with a thickness resolution of the order of Δd = 100 nm can be applied to in situ observations of the catalyst in a PEFC during operation.


Molecular and morphological studies on Contracaecum rudolphii A and C. rudolphii B in great cormorants (Phalacrocorax carbo sinensis) from Italy and Israel.
The distribution of parasites is shaped by a variety of factors, among which are the migratory movements of their hosts. Israel has a unique position to migratory routes of several bird species leaving Europe to winter in Africa, however, detailed studies on the parasite fauna of birds from this area are scarce. Our study investigates occurrence and distribution of sibling species among Contracaecum rudolphii complex in Phalacrocorax carbo sinensis from Italy and Israel, to acquire further information on the geographical range of these species to gain deeper knowledge on the ecology of these parasites and their bird host. A total of 2383 Contracaecum were collected from the gastric mucosa of 28 great cormorants (18 from Israel and 10 from Italy). A subsample was processed for morphological analyses in light and scanning electron microscopy (SEM), and for molecular analyses through amplification and sequencing of the ITS rDNA and the cox2 mtDNA, and through PCR-RFLP. All the 683 Contracaecum subjected to molecular identification belonged to C. rudolphii s.l., (300 C. rudolphii A and 383 C. rudolphii B). SEM micrographs provided, for the first time, details of taxonomic structures in male specimens from both sibling species, and the first SEM characterization of C. rudolphii B. This work presents the first data on the occurrence of sibling species of C. rudolphii in Israel and provides additional information on the distribution of C. rudolphii A and B in Italy, confirming the high prevalence and intensity of infection observed in Ph. carbo sinensis from other Italian areas.


Unbiased degree-preserving randomization of directed binary networks.
Randomizing networks using a naive "accept-all" edge-swap algorithm is generally biased. Building on recent results for nondirected graphs, we construct an ergodic detailed balance Markov chain with nontrivial acceptance probabilities for directed graphs, which converges to a strictly uniform measure and is based on edge swaps that conserve all in and out degrees. The acceptance probabilities can also be generalized to define Markov chains that target any alternative desired measure on the space of directed graphs in order to generate graphs with more sophisticated topological features. This is demonstrated by defining a process tailored to the production of directed graphs with specified degree-degree correlation functions. The theory is implemented numerically and tested on synthetic and biological network examples.


Targeted Droplet-Digital PCR as a Tool for Novel Deletion Discovery at the DFNB1 Locus.
Pathogenic variants at the DFNB1 locus encompassing the GJB2 and GJB6 genes account for 50% of autosomal-recessive, congenital nonsyndromic hearing loss in the United States. Most cases are caused by sequence variants within the GJB2 gene, but a significant number of DFNB1 patients carry a large deletion (GJB6-D13S1830) in trans with a GJB2 variant. This deletion lies upstream of GJB2 and was shown to reduce GJB2 expression by disrupting unidentified regulatory elements. First-tier genetic testing for hearing loss includes GJB2 sequence and GJB6-D13S1830 deletion analysis; however, several other deletions in this locus, each with distinct breakpoints, have been reported in DFNB1 patients and are missed by current panels. Here, we report the development of a targeted droplet digital polymerase chain reaction-based assay for comprehensive copy-number analysis at the DFNB1 locus that detects all deletions reported to date. This assay increased detection rates in a multiethnic cohort of 87 hearing loss patients with only one identified pathogenic GJB2 variant. We identify two deletions, one of which is novel, in two patients (2/87 or 2.3%), suggesting that other pathogenic deletions at the DFNB1 locus may be missed. Mapping the assayed DFNB1 deletions also revealed a ∼ 95 kb critical region, which may harbor the GJB2 regulatory element(s).


Determinants of non-adherence to treatment for tuberculosis in high-income and middle-income settings: a systematic review protocol.
Treatment for tuberculosis (TB) is highly effective if taken according to prescribed schedules. However, many people have difficulty adhering to treatment which can lead to poorer clinical outcomes, the development of drug resistance, increased duration of infectivity and consequent onward transmission of infection. A range of approaches are available to support adherence but in order to target these effectively a better understanding of the predictors of poor adherence is needed. This review aims to highlight the personal, sociocultural and structural factors that may lead to poor adherence in high-income and middle-income settings. Seven electronic databases, Medline, EMBASE, CINAHL, PsycInfo, The Cochrane Library, Scopus and Web of Science, will be searched for relevant articles using a prespecified search strategy. Observational studies will be targeted to explore factors that influence adherence to treatment in individuals diagnosed with TB. Screening title and abstract followed by full-text screening and critical appraisal will be conducted by two researchers. Data will be extracted using the Population, Exposure, Comparator, Outcomes, Study characteristics framework. For cross-study assessment of strength of evidence for particular risk factors affecting adherence we will use the Grading of Recommendations, Assessment, Development and Evaluation tool modified for prognostic studies. A narrative synthesis of the studies will be compiled. A meta-analysis will be considered if there are sufficient numbers of studies that are homogenous in study design, population and outcomes. A draft conceptual framework will be identified that (A) identifies key barriers to adherence at each contextual level (eg, personal, sociocultural, health systems) and (B) maps the relationships, pathways and mechanisms of effect between these factors and adherence outcomes for people with TB. The draft conceptual framework will guide targeting of adherence interventions and further research. CRD42017061049.


Combined ultrasonography and amniocentesis for pregnant women with elevated serum alpha-fetoprotein. Revising the risk estimate.
A combination of ultrasound and amniocentesis for alpha-fetoprotein (AFP) and acetylcholinesterase (ACHE) identified 36 anomalous fetuses among 331 pregnant women evaluated at our center for "true" elevated maternal serum alpha-fetoprotein (MSAFP). In six cases the diagnosis of fetal anomalies was missed on initial ultrasonography. In addition, placental pathology was identified in 12 cases and adverse outcome (fetal demise, intrauterine growth retardation, severe oligohydramnios) in 15. When grouped by multiples of the median (MOM), a significant linear correlation was observed between increasing MSAFP and the rate of fetal anomalies or adverse outcome. The frequency of fetal anomalies increased from 0.93% when MSAFP was less than 3.0 MOM to 56% when MSAFP was greater than 7.5 MOM. No differences were observed in the frequency of placental pathology between the groups. A normal ultrasound study in these patients will decrease considerably, but not eliminate, the risk estimate for undetected fetal anomalies. From our 83% ultrasound sensitivity we calculate that with MSAFP greater than 3.0 MOM the risk of anomalies despite a reassuring scan is greater than 1% and clearly warrants offering amniocentesis for amniotic fluid AFP and ACHE. Between 2.5 and 3.0 MOM the risk is relatively low. Amniocentesis should be offered routinely to patients with MSAFP greater than 3.0 MOM and normal ultrasonography. In patients with MSAFP of 2.5-2.9 MOM and satisfactory ultrasonography the risk of amniocentesis may outweigh its benefits.


Percutaneous Transhepatic Gallbladder Drainage Combined with Laparoscopic Cholecystectomy versus Emergency Laparoscopic Cholecystectomy in Acute Complicated Cholecystitis: Comparison of Curative Efficacy.
Controversy exists on the suitability of laparoscopic cholecystectomy (LC) in acute cholecystitis, especially in patients with severe comorbidities. Recently, many nonsurgical departments have indicated a preference for percutaneous transhepatic gallbladder drainage (PTGBD), but surgeons consider LC as the final treatment option for cholecystitis. This analysis evaluated the curative efficacy of PTGBD in combination with LC as compared with emergency LC (e-LC). We retrospectively analyzed clinical data of 86 patients with acute complicated cholecystitis. Patients were divided into two groups as those who received e-LC and those who underwent PTGBD combined with LC (PTGBD+LC), and baseline characteristics, perioperative data, and operative parameters were compared to check for intergroup differences. Baseline characteristics were similar for the study groups. However, although the operating duration (P = 0.12) and postoperative hospital stay (P = 0.39) did not evidence significant differences, the PTGBD+LC group had significantly better outcomes than the e-LC group with regard to blood loss (P < 0.05), peritoneal drainage duration (P < 0.05), and time to postoperative resumption of oral intake (P < 0.05). Moreover, conversion to open surgery, complications during LC, and mortality rate were all higher in the e-LC group. PTGBD combined with LC is an effective treatment for acute complicated cholecystitis, especially in elderly patients or those with serious comorbidities. To some extent, the curative effect of this method can be considered superior to that of emergency LC.


HolisticKids.org--evolution of information resources in pediatric complementary and alternative medicine projects: from monographs to Web learning.
Use of complementary and alternative medicine (CAM) is growing in the United States. Children are a part of this trend, with adolescent self-care exceeding adult use. As a result, the necessity of educating pediatricians on CAM practices has become clear. This paper describes the Pediatric Integrative Medicine Education (PIME) project with a focus on the creation of HolisticKids.org, a Website designed to educate pediatric residents. HolisticKids.org also addresses the needs and interests of medical students, fellows, faculty, and community-based care providers who work with children and CAM. An outstanding aspect of this effort is its interdisciplinary nature, involving physicians, pharmacists, dieticians, nurses, medical librarians, and Web specialists. Collaboration is mirrored on an institutional level, where the participating institutions include Children's Hospital Boston, Harvard Medical School, Boston Medical Center, the Massachusetts College of Pharmacy and Health Sciences, and Dana Farber Cancer Institute. Now in the third year of development, this Web-based education project demonstrates how integrative medical education can contribute to pediatric care for diverse families and complement cultural competency efforts. Ongoing efforts focus on adding content, developing evaluation techniques, and disseminating this resource to the health sciences community.


Molecular design of the photosystem II light-harvesting antenna: photosynthesis and photoprotection.
The photosystem II (PSII) light-harvesting system carries out two essential functions, the efficient collection of light energy for photosynthesis, and the regulated dissipation of excitation energy in excess of that which can be used. This dual function requires structural and functional flexibility, in which light-harvesting proteins respond to an external signal, the thylakoid DeltapH, to induce feedback control. This process, referred to as non-photochemical quenching (NPQ) depends upon the xanthophyll cycle and the PsbS protein. In nature, NPQ is heterogeneous in terms of kinetics and capacity, and this adapts photosynthetic systems to the specific dynamic features of the light environment. The molecular features of the thylakoid membrane which may enable this flexibility and plasticity are discussed.


Cost evaluation of a two-stage classification procedure.
A two-stage classification rule is suggested for classifying an individual into one of two multivariate normal populations. An individual may be classified using measurements on just the first subset; otherwise the second subset is measured and he is classified using the combined set. On the basis of misclassification costs and costs of collecting observations, the two-stage rule is compared with the usual rules based on the first subset and on the combined set. Comparisons are made for the case of known population parameters and also for the case of unknown population parameters which are estimated from samples. It is assumed throughout that a priori probabilities, cost of misclassification, and cost of making observation are known.


[Application of International Medical Device Electronic Registration].
The eRPS system for medical device registration of National Medical Products Administration was officially launched on June 24, 2019. This paper focused on the following two aspects of the electronic declaration process of medical device regulatory agencies in the whole world:one is whether the electronic submission format is consistent, the other is whether the electronic submission path is convenient. Suggestions are put forward for the next nationwide implementation of the electronic submission so as to speed up the process of the electronization of medical device evaluation in China.


Confronting the issues of therapeutic misconception, enrollment decisions, and personal motives in genetic medicine-based clinical research studies for fatal disorders.
Genetic medicine-based therapies have unlocked the potential for ameliorating diseases previously considered inevitably fatal. Inherent in the clinical trials of genetic medicines are ethical issues of therapeutic misconception, enrollment decisions as they relate to the risks and benefits of research, and the complex relationships among funding sources, investigators, and the families of affected individuals. The purpose of this paper is to help define these complex issues relevant to the use of genetic medicines and to describe the strategy we have used to confront these issues in a phase I trial of adeno-associated virus-mediated gene transfer to the central nervous system of children with late infantile neuronal ceroid lipofuscinosis (LINCL), a fatal lysosomal storage disease associated with progressive neurodegeneration and death by mid-childhood. Our approach to these challenges should provide a useful paradigm for investigators initiating other genetic medicine- based studies to treat inevitably fatal diseases.


Stress and hippocampal plasticity.
The hippocampus is a target of stress hormones, and it is an especially plastic and vulnerable region of the brain. It also responds to gonadal, thyroid, and adrenal hormones, which modulate changes in synapse formation and dendritic structure and regulate dentate gyrus volume during development and in adult life. Two forms of structural plasticity are affected by stress: Repeated stress causes atrophy of dendrites in the CA3 region, and both acute and chronic stress suppresses neurogenesis of dentate gyrus granule neurons. Besides glucocorticoids, excitatory amino acids and N-methyl-D-aspartate (NMDA) receptors are involved in these two forms of plasticity as well as in neuronal death that is caused in pyramidal neurons by seizures and by ischemia. The two forms of hippocampal structural plasticity are relevant to the human hippocampus, which undergoes a selective atrophy in a number of disorders, accompanied by deficits in declarative episodic, spatial, and contextual memory performance. It is important, from a therapeutic standpoint, to distinguish between a permanent loss of cells and a reversible atrophy.


Growing Saccharomyces cerevisiae in calcium-alginate beads induces cell alterations which accelerate glucose conversion to ethanol.
Nongrowing Saccharomyces cerevisiae cells previously grown in alginate exhibit ethanol production rates 1.5 times greater than cells previously grown in suspension. Analysis of glucose, ethanol, and glycerol formation data using quasi-steady-state pathway stoichiometry shows that alginate-grown cells possess phosphofructokinase (PFK), ATPase, and polysaccharide synthesis maximum activities which are approximately two-, two-, and ninefold larger, respectively, than in suspension-grown cells. The estimated change in PFK maximum velocity is consistent with in vitro assays of PFK activity in extracts of suspension- and alginate-grown yeast. Estimation of ethanol production flux control coefficients using in vivo nuclear magnetic resonance (NMR) spectroscopy measurements of intracellular metabolite concentrations and a previously proposed detailed kinetic model of ethanol fermentation in yeast shows that glucose uptake dominates flux control in alginate-grown cells in suspension while earlier research revealed that PFK and ATPase exert significant flux control in suspension-grown cells. When placed in a calcium alginate matrix, alginate-grown cells produced ethanol 1.8 times more rapidly and accumulated substantially more polyphosphate than suspension-grown cells placed in alginate. Cells growing in alginate elicit responses at the genetic level which substantially alter pathway rates and flux control when these cells are used as either a suspended or an immobilized biocatalyst. These responses in gene expression to growth in alginate serve to reconfigure flux controls in alginate to a pattern which is similar to that obtained for suspended-grown cells in suspension.


Value of home blood pressures as predictor of target organ damage in mild arterial hypertension.
Home blood pressure measurement has gained increasing importance for the management of hypertensive patients. The aim of our study was to compare levels of clinic (CBP), ambulatory (ABP), and home blood pressure (HBP) measurements, and their relationships with various indexes of target organ damage in I-II grade essential hypertension. Thirty-eight essential hypertensives underwent evaluation of clinic, ambulatory and home blood pressures. Each patient recorded HBP for 2 days with a digital BP monitor three times daily, the first time on the same day during which ABP monitoring was simultaneously performed. Moreover, in all subjects electrocardiogram recording, echocardiographic study, microalbuminuria assay and fundus oculi examination were obtained. The average HBPs obtained on the first day, in particular systolic values, were quite similar to mean daytime ambulatory BP recorded on the same day. Clinic BP, both systolic and diastolic, showed no significant correlation with left ventricular mass index (LVMI) and with albumin excretion rate (AER), whereas a correlation barely significant was observed with an index of global target organ damage (GTODi), including cardiac, renal and retinal parameters. On the contrary, home blood pressures, especially those recorded on the second day, correlated significantly, and more tightly than clinic BP, with LVMI, AER and GTODi. Our study seems to justify the adoption of home BP monitoring in the management of hypertensive patients, as a useful complement to clinical readings, and may provide additional prognostic information.


Teaching psychosocial care to long-term care nursing assistants.
This article describes a training program that teaches nursing assistants to provide psychosocial care and manage problem behaviors, not just provide basic physical care, for elderly nursing home residents. Addressed are the variety of techniques that can be used to approach nursing assistant students as adult learners in any healthcare setting-long term, acute or home care.


Rts1-protein phosphatase 2A antagonizes Ptr3-mediated activation of the signaling protease Ssy5 by casein kinase I.
Ligand-induced conformational changes of plasma membrane receptors initiate signals that enable cells to respond to discrete extracellular cues. In response to extracellular amino acids, the yeast Ssy1-Ptr3-Ssy5 sensor triggers the endoproteolytic processing of transcription factors Stp1 and Stp2 to induce amino acid uptake. Activation of the processing protease Ssy5 depends on the signal-induced phosphorylation of its prodomain by casein kinase I (Yck1/2). Phosphorylation is required for subsequent Skp1/Cullin/Grr1 E3 ubiquitin ligase-dependent polyubiquitylation and proteasomal degradation of the inhibitory prodomain. Here we show that Rts1, a regulatory subunit of the general protein phosphatase 2A, and Ptr3 have opposing roles in controlling Ssy5 prodomain phosphorylation. Rts1 constitutively directs protein phosphatase 2A activity toward the prodomain, effectively setting a signaling threshold required to mute Ssy5 activation in the absence of amino acid induction. Ptr3 functions as an adaptor that transduces conformational signals initiated by the Ssy1 receptor to dynamically induce prodomain phosphorylation by mediating the proximity of the Ssy5 prodomain and Yck1/2. Our results demonstrate how pathway-specific and general signaling components function synergistically to convert an extracellular stimulus into a highly specific, tuned, and switch-like transcriptional response that is critical for cells to adapt to changes in nutrient availability.


Comparisons of procedural characteristics and clinical outcomes between SMARTTOUCH SURROUNDFLOW catheter and other catheters for atrial fibrillation radiofrequency catheter ablation: a systematic literature review.
SMARTTOUCH SURROUNDFLOW (STSF) catheter is the new generation of SMARTTOUCH (ST) catheter with an upgraded irrigation system for radiofrequency catheter ablation (RFCA) in patients with atrial fibrillation (AF). This systematic literature review searched the major English and Chinese bibliographic databases from 2016 to 2022 for any original clinical studies assessing the STSF catheter for RFCA in AF patients. Meta-analysis with a random effects model was used for evidence synthesis. Pooled outcomes from 19 included studies indicated that STSF catheter was associated with a significantly shorter procedure time (weighted mean difference (WMD): -17.4 min, p<0.001), shorter ablation time (WMD: -6.6 min, p<0.001) and lower catheter irrigation fluid volume (WMD: -492.7 mL, p<0.001) than ST catheter. Pooled outcomes from four included studies with paroxysmal AF patients reported that using the STSF catheter for RFCA was associated with a significantly shorter ablation time (WMD: -5.7 min, p<0.001) and a lower risk of 1-year postablation arrhythmia recurrence (rate ratio: 0.504, p<0.001) than the SURROUNDFLOW (SF) catheter. Significant reductions in procedure time and ablation time associated with the STSF catheter were also reported in the other four studies using non-ST/SF catheters as the control. Overall complications of STSF catheter and control catheters were comparable. Using the STSF catheter was superior to using the ST catheter to conduct RFCA for AF by significantly reducing procedure time, ablation time, fluoroscopy time and irrigation fluid volume. The superiority of the STSF catheter over the SF catheter and other non-ST/SF catheters for RFCA needs further confirmation.


Sulfhydrylcellulose: a new medium for chromatography of mercurated polynucleotides.
We have synthesized a new medium, sulfhydrylcellulose, for affinity chromatography of mercurated polynucleotides. It is the product of reaction between aminoethylcellulose and N-acetylhomocysteine thiolactone. Sulfhydrylcellulose carries up to 90 mumol of SH groups/g and is inexpensive, easy to prepare, and stable. Because it binds mercurated RNA specifically and reversibly and exhibits no size discrimination, sulfhydrylcellulose should have wide applications.


Projective Synchronization of Delayed Neural Networks With Mismatched Parameters and Impulsive Effects.
In this paper, the impulsive effects on projective synchronization between the parameter mismatched neural networks with mixed time-varying delays have been analyzed. Since complete synchronization is not possible due to the existence of parameter mismatch and projective factor, a drive has been taken to achieve the weak projective synchronization of different neural networks under impulsive control strategies. Through the use of matrix measure technique and the extended comparison principle based on the formula of variation of parameters for mixed time-varying delayed impulsive systems, sufficient criteria have been derived for exponential convergence of the networks under the effects of extensive range of impulse. Instead of upper or lower bound of the impulsive interval, the concept of the average impulsive interval is applied to estimate the number of impulsive points in an interval. The concept of calculus is applied for optimizing the synchronization error bounds which are obtained because of different ranges of impulse. Finally, the numerical simulations for various impulsive ranges for different cases are presented graphically to validate the efficiency of the theoretical results.


[Mental health and welfare law to build community support].
While the rest of the world has experienced or completed deinstitutionalization in the turn of the century, Japan has not come up with a clear plan to decrease mental hospital beds. There are 330,000 people in hospitals, and at least 1/3 of them for social reasons. Japanese hospital-centered policy has been enrooted on paternalism that hospitals are responsible for the care of the severely mentally ill. Enactment of Mental Health and Welfare Act in 1995 was epoque making because this law is provided an opportunity for people with psychiatric disabilities to live in the community with support services. With this act, Central government has introduced care guidelines how to coordinate services by care managers in each municipalities in 2002. It is important to address that this new treatment model be based on individual's need and support given to improve an individual's quality of life in the community.


Inferring the Urban Transmission Potential of Bat Influenza Viruses.
Bats are considered natural reservoirs of various, potentially zoonotic viruses, exemplified by the influenza A-like viruses H17N10 and H18N11 in asymptomatic Neotropical bats. These influenza viruses are evolutionarily distinct, are poorly adapted to laboratory mice and ferrets and cannot reassort in vitro with conventional strains to form new influenza subtypes. However, they have attracted renewed attention following reports that their entry in host cells is mediated by the trans-species conserved MHC-II proteins, suggesting that they hold zoonotic potential. Despite the recent studies, the viruses' epidemiology and public health significance remain incompletely understood. Delineating the mechanistic basis of the interactions with their hosts and assessing their global distribution are essential in order to fully assess the zoonotic threat that these strains pose.


Sinus pause during nerve integrity monitoring tube insertion following anesthetic induction with a low-dose neuromuscular blocking agent: A CARE-compliant case report.
Nerve integrity monitoring (NIM) tubes are commonly used in thyroid surgery to prevent recurrent laryngeal nerve injury. To achieve the optimal electromyographic signal for NIM as intraoperative neural monitoring (IONM), the neuromuscular blocking agent (NMBA) dose should be low. The use of a low-dose NMBA increases the anesthetic and analgesic agent dose required to attenuate the laryngeal reflex during intubation. In addition, since the NMBA onset time is delayed, depending on the situation, anesthesia may become excessively deep or shallow before intubation. A 51-year-old woman scheduled for thyroid lobectomy received 0.3 mg/kg of rocuronium. Three minutes later, when the NIM tube was inserted through the vocal cord, the patient's heart rate (HR) was undetectable for 2 seconds. We suspected that the use of a high-dose anesthetic agent and remifentanil or the laryngocardiac reflex induced the sinus pause. To maintain the anesthetic depth, we administered 6 vol% of desflurane. Because the patient's systolic blood pressure was 70 mmHg and HR was 30 beats/min, we discontinued the remifentanil infusion and administered 8 mg of ephedrine. The patient's vital signs recovered to normal levels. Subsequently, there were no episodes of bradycardia or arrhythmia. Sinus pause or severe bradycardia may occur due to the laryngocardiac reflex or the administration of a high-dose anesthetic and analgesic agent during tracheal intubation in patients who received a low-dose NMBA for IONM induction using an NIM tube. Anesthesiologists should be aware of these risks and take precautions to maintain adequate anesthesia, be prepared to administer vasoactive drugs to increase the blood pressure and HR if needed, and, if possible, intravenously administer lidocaine to attenuate the laryngeal reflex during intubation.


Primary thyroid lymphoma: evaluation with CT.
The appearance of primary thyroid lymphoma on computed tomographic (CT) scans and clinical data for 15 patients were analyzed. The CT appearances were classified into three types: 12 patients (80%) had a solitary nodule (type 1), two (13%) had multiple nodules (type 2), and one (7%) had a diffuse goiter (type 3). In 47% of cases, both lobes were involved. The tumors had a strong tendency to compress (80%) or infiltrate (53%) the surrounding structures. The frequency of calcification (7%) or necrosis (7%) was low. Most patients (87%) had a rapidly enlarging thyroid mass, and six (40%) complained of symptoms from obstruction. All patients had coexistent Hashimoto thyroiditis. In 13 of 15 patients (87%), a highly probable diagnosis of thyroid lymphomas was determined with CT and clinical findings. A staging workup with CT and clinical findings confirmed at biopsy will allow appropriate therapy and may lead to improved prognosis for patients with this condition.


Bone density and body composition on the Pacific rim: a comparison between Japan-born and U.S.-born Japanese-American women.
Bone mineral density (BMD) of total body, spine, and proximal femur and the percentage of body fat in 151 U.S.-born Japanese-American women and 137 Japan-born immigrant Japanese-American women living in San Diego, California were measured using dual-energy x-ray absorptiometry. These data were compared with unpublished data from Japanese women obtained in previous studies in Hamamatsu, Japan. The age-adjusted BMD for the spinal level, femoral neck, Ward's triangle, trochanter, and total body, respectively, of U.S.-born Japanese-American women were 10.2, 9.8, 9.9, 9.2, and 2.7% higher than those of native Japanese women. The U.S.-born Japanese-American women had significantly higher body fat than immigrant Japanese-American women. Furthermore, the immigrant women had higher BMD and higher body fat than their native Japanese counterparts; however, no significant total-body BMD differences were found among the three groups after age, height, and weight were adjusted. The U.S.-born Japanese-American women had BMD values equivalent to those of white normals at the spine and femur. Significant life-style differences between U.S.-born and immigrant Japanese-American women were noted. Weight, exercise, early menarche, and years of lifetime estrogen exposure correlated positively with BMD. The significant negative correlates of BMD were age, smoking, and percentage of body fat. Our study presents data suggesting that immigration to the United States has produced a higher BMD in Japanese-American women that is attributable to changes in life-style and diet.


Design and demonstration of fan-out elements generating an array of subdiffraction spots.
We present a design method for diffractive fan-out elements generating an array of subdiffraction spots in a predetermined area using propagating light. A specific constraint is introduced to the Gerchberg-Saxton algorithm to control the dispersion of light energy and the phase of spots. In our demonstration, an element generating a 3 × 3 spot array achieves the spot size reduced to 70% comparing to the diffraction limited spot in simulation and about 80% in the experiment. Various layouts of subdiffraction spots can be made with a high signal to noise ratio using our design method. The relationship between the spot size and the power efficiency is also shown based on the simulation.


IVM of human immature oocytes for infertility treatment and fertility preservation.
Thousands of healthy babies are born from in vitro maturation (IVM) procedures, but the rate of efficiency differs with the source of immature oocytes obtained. Recently, there are different IVM protocols proposed for infertility treatment and fertility preservation. Based on the literature, the clinical application for IVM of immature oocytes was summarized. Immature oocytes may be retrieved from women after priming with or without the use of follicular stimulation hormone (FSH), human chorionic gonadotrophin (hCG) or a combination of both FSH and hCG. Successful pregnancy rates with IVM technology seem to be correlated with the number of immature oocytes obtained. With the source and culture course of immature oocytes, there are various IVM protocols. IVM of immature oocytes is profoundly affected by the culture conditions, but no breakthrough has been made by improving the IVM medium itself. Thus, the clinical application of IVM technology continues to evolve. IVM technology is a useful technique for infertile women and fertility preservation. Mild stimulation IVF combined with IVM of immature oocytes is a viable alternative to the conventional stimulation IVF cycle treatment as it may prove to be an optimal first-line treatment approach.


[Effect of liraglutide on interleukin-1β expression in the pancreatic islets of OLETF rats].
To investigate the effect of liraglutide on the inflammatory cytokine interleukin-1β (IL-1β) and apoptotic factor caspase-3 expression in the pancreatic islets of OLETF rats with impaired glucose tolerance. Twelve-week-old OLETF rats were randomized into 4 groups and received intraperitoneal injections of saline or liraglutide at 50, 100, or 200 µg/kg twice daily for 12 weeks. Eight LETO rats served as the normal control group and received saline injection. After the treatments, the rats were examined for fasting and 30 min plasma insulin during OGTT test, and the expression levels of IL-1β and caspase-3 mRNA and protein in the pancreatic islets were detected by real-time PCR and Western blotting, respectively. Compared with the saline group, liraglutide significantly decreased the expressions of IL-1β and caspase-3 mRNA and protein, and significantly improved the blood glucose, islet β function and early-phase insulin secretion index in OLETF rats. Liraglutide can improve islet function and glucose metabolism partially by inhibiting islet IL-1β expression to delay or prevent the development of diabetes in OLETF rats.


[A case of Vernet's syndrome due to varicella-zoster virus infection].
We report a 73-year-old man who suffered from an acute onset of dysphagia, cough, hoarseness and left facial and occipital pain. On the 44 days of illness, he was admitted to our clinic. A neurological examination revealed left IX, X and XI cranial nerve palsy. The diagnosis of Vernet's syndrome due to varicella-zoster virus (VZV) infection was made, based on the high titers of VZV antibody in serum. Magnetic resonance imaging revealed a unique nodular lesion with gadolinium enhancement at the medial side of the left jugular foramen. Clinical symptoms improved with intravenous high dose pulse methylprednisolone therapy. The clinical course suggests that the inflammation extended from the left X cranial nerve ganglion.


In vivo biofilm on the surface of a surgical mesh implant.
Mesh hernioplasty is among the most frequently performed surgical procedures. The introduction of mesh implants has decreased recurrence rates, but the use of synthetic materials carries the risk of infection and biofilm formation. This paper presents the course of the disease in the case of biofilm formation on the surface of an implanted surgical mesh. Antimicrobial therapy and partial removal of the implant were unsuccessful. Recurring surgical site infection could be managed only through total excision of the infected implant.


Bayesian mixed-effects location and scale models for multivariate longitudinal outcomes: an application to ecological momentary assessment data.
In the statistical literature, the methods to understand the relationship of explanatory variables on each individual outcome variable are well developed and widely applied. However, in most health-related studies given the technological advancement and sophisticated methods of obtaining and storing data, a need to perform joint analysis of multivariate outcomes while explaining the impact of predictors simultaneously and accounting for all the correlations is in high demand. In this manuscript, we propose a generalized approach within a Bayesian framework that models the changes in the variation in terms of explanatory variables and captures the correlations between the multivariate continuous outcomes by the inclusion of random effects at both the location and scale levels. We describe the use of a spherical transformation for the correlations between the random location and scale effects in order to apply separation strategy for prior elicitation while ensuring positive semi-definiteness of the covariance matrix. We present the details of our approach using an example from an ecological momentary assessment study on adolescents.


Preparation of akaganeite nanorods and their transformation to sphere shape hematite.
Akaganeite (beta-FeOOH) nanorods were synthesized through hydrolysis of FeCl3 and FeCl2 solutions containing urea in the temperature range from 90 to 95 degrees C under reflux condition for 8 h. The average diameters and lengths of nanorods were impacted by FeCl2 and urea. Upon heating the solution containing FeCl3, FeCl2 and urea, the average diameters were about 80 nm and lengths of nanorods were about 1.2 microm. The morphologies of beta-FeOOH nanorods in different growth times were shown by TEM images. More interestingly, in the growth process of nanorods, they can self-assemble and form cross structure. The ultrasonic might promote effectively the formation of the nano-cross structure. beta-FeOOH nanorods were calcined and the influence of the calcining temperature and time about the morphology and size of the powder was studied. By heating beta-FeOOH nanorods at 800 degrees C for 6 hours, the hematite in sphere shape was obtained and the forming mechanism was discussed.


Multilevel influences on acceptance of medical male circumcision in Rakai District, Uganda.
Despite access to safe medical male circumcision (MMC) and proven effectiveness of the procedure in reducing acquisition of HIV and other sexually transmitted infections, uptake remains suboptimal in many settings in sub-Saharan Africa, including Rakai District, Uganda. This study explored multilevel barriers and facilitators to MMC in focus group discussions (FGDs) (n = 35 groups) in Rakai. Focus groups were conducted from May through July 2012 with adolescent and adult males, with a range of HIV risk and reproductive health service use profiles, and with adolescent and adult females. Data were analyzed using Atlas.ti and an inductive approach. Participants' discussions produced several key themes representing multilevel influences that may facilitate or create barriers to uptake of MMC. These include availability of MMC services, economic costs, masculine ideals, religion, and social influence. Understanding how males and females view MMC is a crucial step towards increasing uptake of the procedure and reducing disease transmission.


Expression of AMIDASE1 (AMI1) is suppressed during the first two days after germination.
The regulation of cellular auxin levels is a critical factor in determining plant growth and architecture, as indole-3-acetic acid (IAA) gradients along the plant axis and local IAA maxima are known to initiate numerous plant growth responses. The regulation of auxin homeostasis is mediated in part by transport, conjugation and deconjugation, as well as by de novo biosynthesis. However, the pathways of IAA biosynthesis are yet not entirely characterized at the molecular and biochemical level. It is suggested that several biosynthetic routes for the formation of IAA have evolved. One such pathway proceeds via the intermediate indole-3-acetamide (IAM), which is converted into IAA by the activity of specific IAM hydrolases, such as Arabidopsis AMIDASE1 (AMI1). In this article we present evidence to support the argument that AMI1-dependent IAA synthesis is likely not to be used during the first two days of seedling development.


Nonlinear quantum time correlation functions from centroid molecular dynamics and the maximum entropy method.
A new approach for the calculation of nonlinear quantum time correlation functions within the path-integral centroid dynamics formalism is presented. This approach combines information on the real-time dynamics obtained from centroid molecular dynamics with classical operators with information on the corresponding imaginary-time dynamics obtained from path-integral molecular dynamics. Nonlinear quantum correlation functions in the high and low temperature regimes computed for model potentials are in remarkably good agreement with the corresponding exact results, suggesting that the method represents an effective and accurate approach for the investigation of general quantum time correlation functions in systems with many degrees of freedom.


Gordon's syndrome: a case report.
Authors describe a case of syndrome of Gordon, a rare genetic disease characterized by hypertension, hyperkalemia and normal glomerular filtration rate. The potential causes of disease are discussed and literature data are reviewed.


Botulism due to Clostridium baratii type F toxin.
Botulism results from consumption of preformed toxin or in vivo toxin elaboration in wounds or intestine. Of U.S. food-borne botulism cases since 1950, the majority were due to toxin A, but a significant number of suspect cases were never confirmed by culture or toxin detection. We report here a possible case of food-borne botulism attributed to toxin F production by a Clostridium baratii organism isolated from food consumed by the patient. The isolation of a toxin-producing Clostridium species other than Clostridium botulinum from food and stool requires deviation from the usual laboratory protocols, which may account for the lack of complete laboratory confirmation of clinically diagnosed cases.


Myocardial fibrosis in congenital and pediatric heart disease.
Cardiac fibrosis is a common phenomenon in different types of heart diseases, such as ischemic heart disease, inherited cardiomyopathy mutations, diabetes, and ageing and is associated with morbidity and mortality. Increased accumulation of extracellular matrix (ECM) that impacts cardiac function, is the underlying cause of fibrotic heart disease. There are four different types of cardiac fibrosis, including, reactive interstitial fibrosis, replacement fibrosis, infiltrative interstitial fibrosis and endomyocardial fibrosis. They are involved in the activation and transformation of cardiac fibroblasts to myofibroblasts, which participate in ECM production and fibrotic process and several inflammatory pathways. Besides the ECM proteins, myofibroblasts also express smooth muscle α-actin, SM22 and caldesmon and other markers related to fibrotic process. Most commonly employed techniques to assess myocardial fibrosis include stress echocardiography, cardiac magnetic resonance imaging and positron emission tomography. Because of the involvement of renin-angiotensin-II-aldosterone system, transforming growth factor-β signaling and activin-linked kinase 5 in the mechanisms of cardiac fibrosis, these pathways and the involved proteins are useful as therapeutic targets. However, because of the importance of these pathways in many other physiological functions, their therapeutic targeting needs to be approached with caution.


Reviewing the importance of the cold chain in the distribution of vaccines.
Vaccination is an effective public health measure to prevent and control a number of infectious diseases. However, since vaccines are biological products and are sensitive to both heat and cold, they need to be maintained within a narrow range of temperatures, often referred to as the 'cold-chain'. This range, which is between +2°C and +8°C with a target +5°C, does not allow for refreezing or storage at room temperature. This paper discusses the importance of the cold chain, what should be done both to maintain it, and the actions to be taken, should a break be noted. It is important to note the product information supplied with vaccines, which is taken from the summary of product characteristics that forms part of the licensing requirements for each vaccine, and which will state how it should be stored. Using a vaccine that has not been stored according to these instructions constitutes off-label use, for which the individual practitioner must take responsibility. It also emphasises the fragile nature of many public health interventions, maintenance of which require constant vigilance and close cooperation between many groups and individuals.


Body Mass Index Category Moderates the Relationship Between Depressive Symptoms and Diet Quality in Overweight and Obese Rural-Dwelling Adults.
This study was conducted to (1) compare diet quality among depressed and nondepressed overweight and obese rural-dwelling adults and (2) determine whether body mass index (BMI) category moderates the relationship between depressive symptoms and overall diet quality. Rural adults in Kentucky (n = 907) completed the 9-item Patient Health Questionnaire (PHQ-9) that assessed depressive symptoms and a food frequency questionnaire that generated 2005 Healthy Eating Index (HEI) scores. Participants were grouped into overweight (BMI 25-29.9 kg/m2 ) and obese (≥30 kg/m2 ), and nondepressed (PHQ-9 < 10) and depressed (PHQ-9 ≥ 10) groups. Bootstrapped ANCOVAs were used to compare diet quality among the 4 groups. Ordinary least-squares regression using PROCESS was used to determine whether BMI category (overweight vs obese) moderated the association between depressive symptoms and overall diet quality. Overall diet quality was poorer in the obese depressed group than in the obese nondepressed group. Intake of fruit and dark green/orange vegetables and legumes was lower in the obese depressed group than in the overweight nondepressed group. Depressive symptoms predicted poor overall diet quality (B = -0.287, P < .001) and the relationship was moderated by BMI category (coefficient of BMI category* depressive symptom interaction term = 0.355, P < .049). A significant inverse relationship between depressive symptoms and overall diet quality was observed in the overweight group but not in the obese group. Components of diet quality vary according to BMI category and depressive symptom status. The relationship between depressive symptoms and diet quality is influenced by BMI category.


Use of nitroprusside during surgery for thoracoabdominal aortic aneurysm.
To assess the effects of sodium nitroprusside on the deleterious hemodynamic effects of clamping and unclamping of the aorta during resection of thoracoabdominal aortic aneurysm without the use of a shunt, 50 patients were studied. The risk factors included coronary artery disease (44%) associated with previous myocardial infarction (28%), hypertension (70%), congestive heart failure (6%), chronic obstructive pulmonary disease (34%), asthma (2%), and renal insufficiency (2%). Sodium nitroprusside infusion (3 micrograms/kg/min) was started before clamping and discontinued before unclamping of the aorta. The infusion rate was adjusted to maintain blood pressure and pulmonary capillary wedge pressure within the range of control. During cross-clamping cardiac index in the patients remained unchanged and even increased on unclamping, suggesting that left ventricular function was efficiently protected during these periods. All the patients survived the surgery, and the 30 day mortality was only 4%. Our data indicate that major aortic surgery can be carried out safely with the use of nitroprusside rather than of mechanical techniques to provide proximal decompression.


Convolutional Neural Networks in Predicting Nodal and Distant Metastatic Potential of Newly Diagnosed Non-Small Cell Lung Cancer on FDG PET Images.
OBJECTIVE. The purpose of this study was to assess, by analyzing features of the primary tumor with 18F-FDG PET, the utility of deep machine learning with a convolutional neural network (CNN) in predicting the potential of newly diagnosed non-small cell lung cancer (NSCLC) to metastasize to lymph nodes or distant sites. MATERIALS AND METHODS. Consecutively registered patients with newly diagnosed, untreated NSCLC were retrospectively included in a single-center study. PET images were segmented with local image features extraction software, and data were used for CNN training and validation after data augmentation strategies were used. The standard of reference for designation of N category was invasive lymph node sampling or 6-month follow-up imaging. Distant metastases developing during the study follow-up period were assessed by imaging (CT or PET/CT), in tissue obtained from new suspected sites of disease, and according to the treating oncologist's designation. RESULTS. A total of 264 patients with NSCLC participated in follow-up for a median of 25.2 months (range, 6-43 months). N category designations were available for 223 of 264 (84.5%) patients, and M category for all 264. The sensitivity, specificity, and accuracy of CNN for predicting node positivity were 0.74 ± 0.32, 0.84 ± 0.16, and 0.80 ± 0.17. The corresponding values for predicting distant metastases were 0.45 ± 0.08, 0.79 ± 0.06, and 0.63 ± 0.05. CONCLUSION. This study showed that using a CNN to analyze segmented PET images of patients with previously untreated NSCLC can yield moderately high accuracy for designation of N category, although this may be insufficient to preclude invasive lymph node sampling. The sensitivity of the CNN in predicting distant metastases is fairly poor, although specificity is moderately high.


Lack of formation of heterocyclic amines in fumes from frying French fries.
The formation of heterocyclic amines (HAs) in the fumes from frying French fries in soybean oil or lard was studied. A high-pressure liquid chromatography method was used to determine the various HAs in fumes. Results showed that the yields of fumes produced from soybean oil when heated alone for 2 or 4 h were higher than from lard; however, a reversed trend was found when frying French fries in soybean oil and lard. Most fumes from soybean oil and lard while frying French fries were adsorbed onto the condensation apparatus, while the other portions were adsorbed onto the wool and glass beads, which were incorporated in our experimental design for collecting the fumes. The fumes from soybean oil when heated alone were found to contain three HAs, namely, 2-amino-3-methylimidazo[4,5-f]quinoxaline (IQx), 2-amino-3-methylimidazo[4,5-f ]quinoline (IQ), and 1-methyl-9H-pyrido[4,3-b ]indole (Harman), whereas two more HAs, 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) and 3-amino-1,4-dimethyl-5H-pyrido[4,3-b ]indole (Trp-P-1), were generated in lard. Lard was more susceptible to the formation of HAs than soybean oil when both were heated alone. No HAs were detected in the fumes from French fries fried in soybean oil and lard.


Pulse operation of linearly polarized diode-pumped cesium-vapor laser based on acousto-optical modulation.
We present a pulse linearly polarized diode-pumped cesium-vapor laser (Cs-DPAL) based on an acousto-optical modulator (AOM) for the first time. The continuous wave (CW) performance of the Cs-DPAL was first investigated, and ~1.05 W linearly polarized CW laser was obtained. Next, we applied a rectangular signal to modulate the AOM. The Cs-DPAL realized a pulse laser output with a maximum repetition rate of 1 MHz and minimum pulse duration of 238 ns. To the best of our knowledge, this is the highest repetition rate reported thus far for a diode-pumped alkali-vapor laser (DPAL). The maximum output power of the pulse laser reached ~0.20 W, and the corresponding Mx 2 and My 2 factors were 1.31 and 1.19, respectively. Finally, we realized code modulation of the Cs-DPAL, with a maximum bit rate of 2 Mb/s.


Zebra Mussel Spawning Is Induced in Low Concentrations of Putative Serotonin Reuptake Inhibitors.
Serotonin (5-hydroxytryptamine, 5-HT) and its receptor ligands induce both oocyte maturation and spawning in zebra mussels (Dreissena polymorpha). The selective serotonin reuptake inhibitors (SSRIs) fluvoxamine ("Luvox"), fluoxetine ("Prozac"), and paroxetine ("Paxil") are commonly prescribed drugs for the treatment of depression in humans. They act to increase 5-HT neurotransmission by inhibiting reuptake transport proteins at synapses. I tested the efficacy of these drugs at inducing spawning in zebra mussels. All three compounds induced spawning in both sexes at concentrations lower than that for 5-HT itself. Fluvoxamine was particularly potent, inducing spawning in 100% of both sexes at 10-5 and 10-6 M. The concentration that induced a significant percentage of animals to spawn was as low as 10-9 M for males and and 10-7 M for females. The lowest concentration of fluvoxamine to induce spawning was 10-8 M for females (40%) and 10-10 M for males (20%). Gametes spawned in fluvoxamine (10-5 M and lower) were viable, and swimming trochophores were formed within 20 hours. Fluoxetine was also an effective spawning inducer, causing 100% of males to spawn at 5 x 10-6 M. The concentration of fluoxetine required to induce a significant percentage of spawning was as low as 5 x 10-8 M for males and 5 x 10-6 M for females. In both fluvoxamine and fluoxetine, more than 60% of the males spawned within the first hour of exposure. In contrast, paroxetine was a weak spawning inducer. At concentrations of 10-5 and 10-6 M it induced significant, but low (50% and 40%, respectively) percentages of males to spawn. Paroxetine did not induce significant spawning in females. Thus, fluvoxamine, fluoxetine, and paroxetine can induce spawning at low concentrations, and fluvoxamine is the most powerful spawning inducer in any bivalve. These may be useful agents for stimulating invertebrate serotonergic mechanisms without applying exogenous 5-HT, and they are potentially important in bivalve aquaculture. Moreover, these results suggest, for the first time, the presence of 5-HT reuptake transporters in bivalve molluscs.


AI-Assisted Ultra-High-Sensitivity/Resolution Active-Coupled CSRR-Based Sensor with Embedded Selectivity.
This research explores the application of an artificial intelligence (AI)-assisted approach to enhance the selectivity of microwave sensors used for liquid mixture sensing. We utilized a planar microwave sensor comprising two coupled rectangular complementary split-ring resonators operating at 2.45 GHz to establish a highly sensitive capacitive region. The sensor's quality factor was markedly improved from 70 to approximately 2700 through the incorporation of a regenerative amplifier to compensate for losses. A deep neural network (DNN) technique is employed to characterize mixtures of methanol, ethanol, and water, using the frequency, amplitude, and quality factor as inputs. However, the DNN approach is found to be effective solely for binary mixtures, with a maximum concentration error of 4.3%. To improve selectivity for ternary mixtures, we employed a more sophisticated machine learning algorithm, the convolutional neural network (CNN), using the entire transmission response as the 1-D input. This resulted in a significant improvement in selectivity, limiting the maximum percentage error to just 0.7% (≈6-fold accuracy enhancement).


Tempo and walking speed with music in the urban context.
The study explored the effect of music on the temporal aspects of walking behavior in a real outdoor urban setting. First, spontaneous synchronization between the beat of the music and step tempo was explored. The effect of motivational and non-motivational music (Karageorghis et al., 1999) on the walking speed was also studied. Finally, we investigated whether music can mask the effects of visual aspects of the walking route environment, which involve fluctuation of walking speed as a response to particular environmental settings. In two experiments, we asked participants to walk around an urban route that was 1.8 km in length through various environments in the downtown area of Hradec Králové. In Experiment 1, the participants listened to a musical track consisting of world pop music with a clear beat. In Experiment 2, participants were walking either with motivational music, which had a fast tempo and a strong rhythm, or with non-motivational music, which was slower, nice music, but with no strong implication to movement. Musical beat, as well as the sonic character of the music listened to while walking, influenced walking speed but did not lead to precise synchronization. It was found that many subjects did not spontaneously synchronize with the beat of the music at all, and some subjects synchronized only part of the time. The fast, energetic music increases the speed of the walking tempo, while slower, relaxing music makes the walking tempo slower. Further, it was found that listening to music with headphones while walking can mask the influence of the surrounding environment to some extent. Both motivational music and non-motivational music had a larger effect than the world pop music from Experiment 1. Individual differences in responses to the music listened to while walking that were linked to extraversion and neuroticism were also observed. The findings described here could be useful in rhythmic stimulation for enhancing or recovering the features of movement performance.


Purification and immunological characterization of a rhamnose-glucose antigen from Streptococcus mutans 6517-T2 (serotype g).
The serotype antigens of Streptococcus mutans have been described as cell wall-associated polysaccharides. In this study, an additional wall polysaccharide antigen was purified and characterized from S. mutans strain 6715-T2, a mutant of 6715 (serotype g). Strain 6715-T2 lost the serotype antigen during animal passage. Rhamnose-containing carbohydrate fractions were solubilized from bacterial cells by extraction with 5% trichloroacetic acid at 4 degrees C for 18 h and with 0.01 N HCl at 100 degrees C for 20 min. Extracts were combined and purified on columns of diethylaminoethyl-Sephadex A-25 and Sephadex G-100. The purified sample contained 59% rhamnose, 31% glucose, 2.2% protein, and 0.24% phosphorus. The purified rhamnose-glucose polysaccharide (RGP/6715-T2) reacted strongly with antisera to whole cells of 6715-T2. Agar gel diffusion and comparative immunoelectrophoresis studies revealed that RGP/6715-T2 was serologically distinct from the serotype g and d polysaccharide antigens. These techniques also indicated immunological identity between RGP/6715-T2 and RGP/B13, a rhamnose-glucose polymer previously isolated from S. mutans B13, a serotype d strain. Antigen immunologically identical to RGP/6715-T2 was detected both in Rantz-Randall extracts from whole cells of S. mutans strains 6715, OMZ-65, and 6715-PT and in extracts from cells of 6715-T2 and C307, two mutant serotype g strains that lacked the serotype g antigen.


A Systematic Investigation of Lateral Estimation Using Various Interpolation Approaches in Conventional Ultrasound Imaging.
Accurate lateral displacement and strain estimation is critical for some applications of elasticity imaging. Typically, motion estimation in the lateral direction is challenging because of low sampling frequency and lack of phase information in conventional ultrasound imaging. Several approaches have been proposed to improve the performance of lateral estimation, such as lateral interpolation on the radio frequency (RF) signals (Interp_RF), lateral interpolation on the cross-correlation function (Interp_CCF), and lateral interpolation on both the RF signals and cross-correlation function (Interp_Both). In this paper, the estimation performances of the above-mentioned three approaches are compared systematically in simulations and phantom experiments. In the simulations, the root-mean-square error (RMSE) of axial/lateral displacement and strain is utilized to assess the accuracy of motion estimation. In the phantom experiments, the displacement quality metric (DQM), defined as the normalized cross-correlation between the motion-compensated reference frame and the comparison frame, and the contrast-to-noise ratio (CNR) of axial/lateral strain are used as the evaluation criteria. The results show that the three approaches have similar performance in axial estimation. For lateral estimation, if the line density of ultrasound imaging is relatively high (i.e., >4.2 lines/mm), Interp_CCF is comparable to Interp_Both, and Interp_RF performs the worst. However, if the line density is relatively low (i.e., <2.8 lines/mm), Interp_Both performs the best as indicated by the lowest RMSEs or highest DQMs and CNRs in lateral estimation. The trend is consistent at different window sizes, applied strains, and sonographic signal-to-noise ratios (>20 dB). Besides, Interp_Both with a small interpolation factor (e.g., 3-5) is found to obtain the best tradeoff between the estimation accuracy and the computational cost, and thus is suggested for lateral motion estimation in the case of a low line density (i.e., <2.8 lines/mm).