[A case of primary acute pulmonary cavitation in sarcoidosis complicated by multiple nodular lesions in the central nervous system].
A 20-year-old man visited our hospital complaining of headache and a dry cough. Chest X-ray and chest CT showed bilateral hilar and mediastinal lymphadenopathy, multiple cavitations with thin, smooth walls, and diffuse granular shadows. A transbronchial biopsy specimen revealed sarcoid granuloma. Primary acute pulmonary cavitation of sarcoidosis was diagnosed, since there was no evidence of infection, emphysematous change, fibrotic or cystic bronchiectatic change on chest X-ray. EEG, contrast enhancement of brain CT scans and MRI were performed because the patient complained of headache. EEG showed a high voltage paroxysmal slow wave and giant build-up, whereas brain CT showed no abnormalities. T1-weighted MRI with gadolinium enhancement showed multiple high intensity nodules in the convexity, brain stem, and spinal cord. Corticosteroid therapy (60 mg/day) was started. After 1 week of treatment, the headache ceased. After 2 weeks of treatment, both the cavities in the lung field's and the nodules in the central nervous system disappeared. Therefore, the dose of corticosteroids was gradually reduced to a maintenance dose of 5 mg/day, and no relapse was noted. We report a very rare case of primary acute pulmonary cavitation in sarcoidosis complicated by multiple nodular lesions in the central nervous system.


A reliability and utility study of the care dependency scale.
The purpose of this study was to examine the reliability and utility of the Care Dependency Scale (CDS). This 15-item scale has been developed recently for assessing the care dependency of demented or mentally handicapped inpatients. Data for this study were collected from 153 demented and 139 mentally handicapped inpatients. The sample was measured three times. Internal consistency was determined using Cronbach's alpha and ranged from 0.95 to 0.97. Interrater reliability revealed moderate to substantial weighted Kappa statistics between 0.51 and 0.83. Test-retest reliability analysis resulted in substantial weighted Kappas between 0.66 and 0.89. Utility tests also revealed satisfactory results. The findings support the reliability and utility of the CDS.


A self-contained polymeric cartridge for automated biological sample preparation.
Sample preparation is one of the most crucial processes for nucleic acids based disease diagnosis. Several steps are required for nucleic acids extraction, impurity washes, and DNA/RNA elution. Careful sample preparation is vital to the obtaining of reliable diagnosis, especially with low copies of pathogens and cells. This paper describes a low-cost, disposable lab cartridge for automatic sample preparation, which is capable of handling flexible sample volumes of 10 μl to 1 ml. This plastic cartridge contains all the necessary reagents for pathogen and cell lysis, DNA/RNA extraction, impurity washes, DNA/RNA elution and waste processing in a completely sealed cartridge. The entire sample preparation processes are automatically conducted within the cartridge on a desktop unit using a pneumatic fluid manipulation approach. Reagents transportation is achieved with a combination of push and pull forces (with compressed air and vacuum, respectively), which are connected to the pneumatic inlets at the bottom of the cartridge. These pneumatic forces are regulated by pinch valve manifold and two pneumatic syringe pumps within the desktop unit. The performance of this pneumatic reagent delivery method was examined. We have demonstrated the capability of the on-cartridge RNA extraction and cancer-specific gene amplification from 10 copies of MCF-7 breast cancer cells. The on-cartridge DNA recovery efficiency was 54-63%, which was comparable to or better than the conventional manual approach using silica spin column. The lab cartridge would be suitable for integration with lab-chip real-time polymerase chain reaction devices in providing a portable system for decentralized disease diagnosis.


Identification of the principal serological immunodeterminants of African swine fever virus by screening a virus cDNA library with antibody.
Protective immunity to African swine fever virus (ASFV) may involve a combination of both serological and cellular mechanisms. This work is focused on the identification of the possible relevant serological immunodeterminants of immunity. Thus, 14 serological immunodeterminants of ASFV have been characterized by exhaustive screening of a representative lambda phage cDNA expression library of the tissue culture-adapted Ba71V strain of ASFV. The library was constructed using RNA extracted from Vero cells infected for 3, 6, 9 and 12 h. A total of 150 clones was selected arbitrarily by antibody screening of the library with a polyclonal antiserum from a domestic pig surviving infection with the virulent Malta isolate of ASFV. Sequencing of these clones permitted identification of 14 independent viral proteins that stimulated an antibody response. These included six proteins encoded by previously unassigned open reading frames (ORFs) (B602L, C44L, CP312R, E184L, K145R and K205R) as well as some of the more well-studied structural (A104R, p10, p32, p54 and p73) and non-structural proteins (RNA reductase, DNA ligase and thymidine kinase). Immunogenicity of these proteins was confirmed by demonstrating the corresponding antibodies in sera from pigs infected either with the Malta isolate or with the OURT88/3-OURT88/1 isolate combination. Furthermore, the majority of these ORFs were also recognized by immune antiserum from the natural host, the bush pig, following secondary challenge with the virulent Malawi (SINT90/1) isolate of ASFV. Thus, it is possible that some of these determinants may be important in protection against virus infection.


Understanding the Inguinal Sinus in Sheep (Ovis aries)-Morphology, Secretion, and Expression of Progesterone, Estrogens, and Prolactin Receptors.
Post-parturient behavior of mammalian females is essential for early parent-offspring contact. After delivery, lambs need to ingest colostrum for obtaining the related immunological protection, and early interactions between the mother and the lamb are crucial. Despite visual and auditory cues, olfactory cues are decisive in lamb orientation to the mammary gland. In sheep, the inguinal sinus is located bilaterally near the mammary gland as a skin pouch (IGS) that presents a gland that secretes a strong-smelling wax. Sheep IGS gland functions have many aspects under evaluation. The objective of the present study was to evaluate sheep IGS gland functional aspects and mRNA transcription and the protein expression of several hormone receptors, such as progesterone receptor (PGR), estrogen receptor 1 (ESR1), and 2 (ESR2) and prolactin receptor (PRLR) present. In addition, another aim was to achieve information about IGS ultrastructure and chemical compounds produced in this gland. All hormone receptors evaluated show expression in IGS during the estrous cycle (follicular/luteal phases), pregnancy, and the post-partum period. IGS secretion is rich in triterpenoids that totally differ from the surrounding skin. They might be essential substances for the development of an olfactory preference of newborns to their mothers.


Alteration of high pressure nervous syndrome in rats by alteration of colonic temperature.
The components of the high pressure nervous syndrome (HPNS) have been clearly described previously. Animal studies of HPNS, however, have been characterized by nonstandardized definitions of the various HPNS parameters, based on visual observations. Where EEG's have been used in HPNS studies, the frequent occurrence of movement-induced artifact has made much of the data difficult to interpret. Because of these limitations, efforts to clarify the influence of environmental variables on the syndrome have led to varying results, especially with respect to the influence of temperature. The technique used in this study consistently yielded artifact-free EEGs from unanesthetized, moving rats during simulated heliox dives. Typical seizure patterns in the EEG recordings were combined with clinical seizure activity to define HPNS convulsion-threshold pressure (Pc). By manipulating body temperature artificially, three groups of rats were investigated--hypothermic, euthermic, and hyperthermic animals. An inverse relationship between body temperature and HPNS convulsion-threshold pressure was demonstrated.


Therapeutic exercise for people with osteoarthritis of the hip or knee. A systematic review.
To determine whether land based therapeutic exercise is beneficial for people with osteoarthritis (OA) of the hip or knee in terms of reduced joint pain, improved physical function, and/or the patient's global assessment of therapeutic effectiveness. Five databases were searched for randomized clinical trials. Standardized mean differences (SMD) with their 95% confidence intervals (CI) were calculated for each study and then combined using a fixed effects model. Only 2 studies, totaling about 100 participants, could potentially provide data on people with hip OA. Fourteen studies provided data on 1633 participants with knee OA. Nine of these studies were considered of high methodological quality. For pain, combining the results revealed a mean moderate beneficial effect (SMD 0.46, 95% Cl 0.35, 0.57), while for self-reported physical function a mean small beneficial effect (SMD 0.33, 95% CI 0.23, 0.43) was found. These results appeared to be sensitive to blinding of outcome assessor and choice of control group. Land based therapeutic exercise was shown to reduce pain and improve physical function for people with OA of the knee.


Acceleration of pro-caspase-3 maturation and cell migration inhibition in human breast cancer cells by phytoconstituents of Rheum emodi rhizome extracts.
The aggressive nature of estrogen receptor (ER)-negative breast cancer subtype obligates for innovative targeted therapies. The present study aimed to investigate the phytoconstituents and specific anticancer activities of Rheum emodi rhizome, a known food source used locally to treat various ailments. Petroleum ether extracts (hot [PHR] and cold [PCR]) of R. emodi, exhibited significant free radical scavenging potentials through DPPH and reducing power assays, rendering them as good sources of antioxidants. The extracts, PHR and PCR had shown significant (P < 0.05) cancer-cell-specific cytotoxicity in the assayed cells (MDA-MB-231 [breast carcinoma] and WRL-68 [non-tumoral]) at 100 μg/ml, and 50 and 100 μg/ml concentrations respectively. Extracts also induced fervent apoptosis in ER-negative cells (MDA-MB-231) compared to ER-positive subtype (MCF-7), and found to involve CPP32/caspase-3 in its apoptosis induction mechanism. Moreover, extracts had an inevitable potential to inhibit the migration of metastatic breast cancer cells (MDA-MB-231) in vitro. Further, the active principles of extracts were identified through HPLC and GC-MS analysis to reveal major polyphenolics, 4,7-Dimethyl-(octahydro)indolo[4,3-fg]quinolin-10-one, 5-Oxo-isolongifolene, Valencene-2, and other quinone, quinoline and anthraquinone derivatives. The extracts are thus good candidates to target malignant ER-negative breast cancer, and the identified phytoconstituents could be eluted in further exploratory studies for use in dietary-based anti-breast cancer therapies.


Isoflavone phytoestrogen degradation in fermented soymilk with selected beta-glucosidase producing L. acidophilus strains during storage at different temperatures.
Soymilk fermented with 3 selected Lactobacillus acidophilus strains were stored at various temperatures (-80 degrees C, 4 degrees C, 25 degrees C and 37 degrees C) for 8 weeks and the concentration of isoflavones determined weekly using RP-HPLC. The decreasing concentration of isoflavones in soymilk during storage due to degradation was found to fit the first order kinetics model. Isoflavone aglycones as well as isoflavone glucosides largely appeared to be stable during storage (P<0.01). Interestingly, the aglycone forms showed much smaller degradation as compared to glucoside forms at all the storage temperatures studied. Of the isoflavone aglycones, daidzein was found to be the most stable followed by genistein, while glycitein was least stable. Isoflavone aglycones such as glycitein, daidzein and genistein showed smaller degradation constants in fermented soymilk at lower storage temperatures (-80 degrees C and 4 degrees C) and higher degradation constants at higher storage temperatures (25 degrees C and 37 degrees C) with each strain. In contrast, glucosides glycitin and daidzin showed higher degradation at lower storage temperatures (-80 degrees C and 4 degrees C) and lower degradation at higher storage temperatures (25 degrees C and 37 degrees C). Storage temperature was therefore found to be very important in regulating the rate of degradation soy isoflavones in fermented soymilk.


Correlation between twitching motility and possession of polar fimbriae in Acinetobacter calcoaceticus.
Negatively stained preparations of 16 strains of Acinetobacter calcoaceticus were examined in the electron microscope. Five of the strains did and 11 of the strains did not exhibit twitching motility. Two of the non-twitching strains were substrains of twitching wild-type strains. All twitching strains were found to possess fimbriae with a diameter of approximately 50 A. These fimbriae were shown to be of polar origin except in one strain where, for technical reasons, the origin could not be determined with certainty. Polar fimbriae could not be demonstrated in any of the strains that did not exhibit twitching motility. The demonstration of polar fimbriae was only regularly possible during the exponential growth phase, presumably because the fimbriae are shed by the bacteria during later growth phases. During the study, methods were developed for securing exponentially growing bacteria in concentrations suited for the preparation of negatively stained cells for electron microscopy. Peritrichously arranged fimbriae with a diameter of approximately 30 A were demonstrated in nearly all strains studied, especially on cells in late growth phases. The occurrence of this kind of fimbriae was therefore not correlated with the occurrence of twitching motility.


Laccase pretreatment of wheat straw: effects of the physicochemical characteristics and the kinetics of enzymatic hydrolysis.
Wheat straw, the most abundant lignocellulosic biomass in China, is rich in cellulose that can be hydrolyzed and then converted into biofuels, such as bioethanol and biohydrogen. However, the accessibility of cellulose and the enzyme activity are greatly reduced in the presence of lignin. This significantly increases the enzyme cost in the saccharification, which hampers industrial production of lignocellulosic biofuels. In this study, a laccase treatment system mediated by 1-hydroxybenzotriazole was employed to modify and degrade lignin to enhance subsequent enzymatic saccharification of wheat straw. A kinetic model considering enzyme adsorption on lignin was proposed to estimate the saccharification performance. Fourier transform infrared spectroscopy (FTIR) analyses showed that the peak intensity of lignin structure characteristics significantly changed after laccase-mediated system (LMS) treatment. 2D-nuclear magnetic resonance (NMR) analyses indicated that the aromatic ether bonds were cleaved and that guaiacyl (G) was oxidized after LMS treatment. X-ray diffraction (XRD) analyses suggested that the crystallinity of lignocellulose increased due to the partial degradation of lignin. As a result, the nonproductive adsorption of the enzyme on lignin was reduced by 28%, while the reducing sugar yield increased by 26%. A semi-empirical kinetic model was used to estimate the reducing sugar yield, the initial hydrolysis rate (K M ) and deactivation rate coefficient (α) of LMS-pretreated wheat straw were 0.157 (h-1) and 0.214 (h-1), respectively. The model showed high accuracy (predicting error < 10%) for describing the behavior of laccase-treated wheat straw hydrolysis when the solid loading is < 5%. The adsorption ability of the enzyme to lignin was reduced after LMS pretreatment. Physicochemical analyses showed that the chemical groups of lignin and lignocellulose were changed, with the crystallinity of the lignocellulose increasing after LMS treatment. A semi-empirical kinetic model was proposed to estimate the reducing sugar yield, which showed high accuracy for predicting the hydrolysis performance of laccase-treated wheat straw.


Two cases of adult-onset Still's disease treated with tocilizumab that achieved tocilizumab-free remission.
There have been many previously reported cases of adult-onset Still's disease (AOSD) which were successfully treated with tocilizumab (TCZ). However, the efficacy and safety of TCZ therapy for AOSD-associated macrophage activation syndrome (MAS), and the optimal duration of TCZ therapy, remain unclear. We herein report two cases of refractory AOSD, one of which was associated with MAS. These two patients were treated with TCZ, and the withdrawal of TCZ was planned according to the serum interleukin-6 level, which resulted in TCZ-free remission.


Machine learning models to predict traumatic brain injury outcomes in Tanzania: Using delays to emergency care as predictors.
Constraints to emergency department resources may prevent the timely provision of care following a patient's arrival to the hospital. In-hospital delays may adversely affect health outcomes, particularly among trauma patients who require prompt management. Prognostic models can help optimize resource allocation thereby reducing in-hospital delays and improving trauma outcomes. The objective of this study was to investigate the predictive value of delays to emergency care in machine learning based traumatic brain injury (TBI) prognostic models. Our data source was a TBI registry from Kilimanjaro Christian Medical Centre Emergency Department in Moshi, Tanzania. We created twelve unique variables representing delays to emergency care and included them in eight different machine learning based TBI prognostic models that predict in-hospital outcome. Model performance was compared using the area under the receiver operating characteristic curve (AUC). Inclusion of our twelve time to care variables improved predictability in each of our eight prognostic models. Our Bayesian generalized linear model produced the largest AUC, with a value of 89.5 (95% CI: 88.8, 90.3). Time to care variables were among the most important predictors of in-hospital outcome in our best three performing models. In low-resource settings where delays to care are highly prevalent and contribute to high mortality rates, incorporation of care delays into prediction models that support clinical decision making may benefit both emergency medicine physicians and trauma patients by improving prognostication performance.


Nomogram including tumor deposition count to noninvasively evaluate the prognosis of rectal cancer patients: A retrospective study.
To build a nomogram model that includes tumor deposition (TDs) count to noninvasively evaluate the prognosis of patients with rectal cancer (RC). A total of 262 patients between January 2013 and December 2018 were recruited and divided into 2 cohorts: training (n = 171) and validation (n = 91). Axial portal venous phase computed tomography images were used to extract radiomic features, and the least absolute shrinkage and selection operator-Cox analysis was applied to develop an optimal radiomics model to derive the Rad-score. A Cox regression model combining clinicopathological factors and Rad-scores was constructed and visualized using a nomogram. And its ability to predict RC patients' survival was tested by Kaplan-Meier survival analysis. The time-dependent concordance index curve was used to demonstrate the differentiation degree of model. Calibration and decision curve analyses were used to evaluate the calibration accuracy and clinical usefulness of the nomogram model, and the prediction performance of the nomogram model was compared with the clinical and radiomics models using the likelihood test. Computed tomography-based Rad-score, pathological tumor (pT) stageT4, and TDs count were independent risk factors affecting the prognosis of RC. The whole concordance index of the nomogram model for predicting the overall survival rates of RC was higher than that of the clinical and radiomics models in the training (0.812 vs 0.59, P = .019; 0.812 vs 0.714, P = .014) and validation groups (0.725 vs 0.585, P = .002; 0.725 vs 0.751, P = .256). The nomogram model could effectively predict patients' overall survival rate (hazard ratio = 9.25, 95% CI = [1.17-72.99], P = .01). The nomogram model also showed a higher clinical net benefit than the clinical and radiomics models in the training and validation groups. The nomogram model developed in this study can be used to noninvasively evaluate the prognosis of RC patients. The TDs count is an independent risk factor for the prognosis of RC.


Specific interferon γ detection for the diagnosis of previous Q fever.
Current practice for diagnosis of Q fever, caused by the intracellular pathogen Coxiella burnetii, relies mainly on serology and, in prevaccination assessment, on skin tests (STs), which both have drawbacks. In this study, C. burnetii-specific interferon γ (IFN-γ) production was used as a new diagnostic tool for previous Q fever, circumventing most of these drawbacks. Our aim was to compare this test to serology and ST. One thousand five hundred twenty-five individuals from an endemic area with a risk for chronic Q fever were enrolled. IFN-γ production was measured after in vitro stimulation of whole blood with C. burnetii antigens. Various formats using different C. burnetii antigens were tested. Serology and ST were performed in all individuals. In all assay formats, C. burnetii-specific IFN-γ production was higher (P < .0001) in seropositive or ST-positive subjects than in seronegative and ST-negative subjects. Whole blood incubated for 24 hours with C. burnetii Nine Mile showed optimal performance. After excluding subjects with equivocal serology and/or borderline ST results, IFN-γ production was 449 ± 82 pg/mL in the positive individuals (n = 219) but only 21 ± 3 pg/mL in negative subjects (n = 908). Using Bayesian analysis, sensitivity and specificity (87.0% and 90.2%, respectively) were similar to the combination of serology and ST (83.0% and 95.6%, respectively). Agreement with the combination of serology and ST was moderate (84% concordance; κ = 0.542). Specific IFN-γ detection is a novel diagnostic assay for previous C. burnetii infection and shows similar performance and practical advantages over serology and ST. Future studies to investigate the clinical value in practice are warranted.


Ventilation and ventilators--an update.
In the five years which have passed since the previous review, the literature has been concerned more with the ways in which ventilators may be applied to patients and the effects of differing patterns of ventilation than with the design philosophy of the ventilators themselves. This account should be read in conjunction with that of 1982 [1].


Arthroscopic treatment for greater tuberosity fractures: rationale and surgical technique.
A description of a new technique for arthroscopic treatment of minimally displaced greater tuberosity fractures of the humerus and associated soft tissue lesions is presented. This kind of fracture is usually treated nonsurgically. However, recent evidence suggests that even a small amount of superior displacement may produce shoulder dysfunction and require a perfect surgical reduction and fixation. Moreover, any displaced fracture of the greater tuberosity presents a high rate of associated and largely undetected soft tissue lesions. To avoid underestimating accompanying soft tissue pathology, arthroscopic assessment before open treatment of greater tuberosity fractures has been suggested. In 2 earlier case reports, we described the use of an arthroscope not only to diagnose and treat a rotator cuff tear and a Bankart lesion associated with a minimally displaced greater tuberosity fracture but also to arthroscopically reduce and treat the fracture. With advancements in arthroscopy and equipment, we refined and systematized the original arthroscopic technique that we have routinely used since 1997. This article presents the new technique.


Bioactive Metabolites Produced by Pseudonocardia endophytica VUK-10 from Mangrove Sediments: Isolation, Chemical Structure Determination and Bioactivity.
Chemical investigation of the actinobacterial isolate Pseudonocardia endophytica VUK-10 has led to the segregation of two known bioactive compounds, namely 4-(2-acetamidoethyl) phenyl acetate and 4-((1, 4-dioxooctahydropyrrolo [1, 2-a] pyrazin-3-yl) methyl) phenyl acetate. The strain was isolated from a sediment sample of the Nizampatnam mangrove ecosystem, south coastal Andhra Pradesh, India. The chemical structure of the active compounds was established on the basis of spectroscopic analysis, including (1)H NMR and (13)C NMR spectroscopies, FTIR, and EIMS. The antimicrobial and cytotoxic activities of the bioactive compounds produced by the strain were tested against opportunistic and pathogenic bacteria and fungi and on MDA-MB-231, OAW, HeLa, and MCF-7 cell lines. The compounds exhibited antimicrobial activities against gram-positive and gram-negative bacteria and fungi and also showed potent cytotoxic activity against MDA-MB-231, OAW, HeLa, and MCF-7 cell lines. This is the first example for this class of bioactive compounds isolated from Pseudonocardia of mangrove origin.


The G1 cell cycle arrest of macrophages infected with Aggregatibacter actinomycetemcomitans.
Infection of murine macrophage cell line J774.1 with the periodontopathic bacterium Aggregatibacter actinomycetemcomitans induces apoptotic cell death. The infection induces cell cycle arrest in the G1 phase prior to the appearance of apoptotic cells. This study determined the involvement of various cell cycle-related signal molecules in A. actinomycetemcomitans-induced G1 cell cycle arrest. Cell cycle in J774.1 cells infected with A. actinomycetemcomitans was analyzed with a flow cytometer. Immunoblot analysis was also employed to determine the expression levels of intracellular signal molecules. Flow cytometric analysis revealed that the percentage of cells in the G1 phase increased to 77.2% at 12 h after A. actinomycetemcomitans infection. Additionally, according to immunoblot analysis, expression levels of hyperphosphorylated forms of retinoblastoma protein (ppRb) declined in J774.1 cells following A. actinomycetemcomitans infection, whereas hypophosphorylated Rb (pRb) expression levels were elevated slightly. Expression levels of cyclin D1 and D2 in the cells decreased gradually postinfection; CDK2, CDK4, CDK6 and cyclin E levels were not changed. Furthermore, postinfection, p21(CIP1/WAF1) expression increased at 6 h, followed by a subsequent decrease. These findings suggest that cyclin D1 and D2 and p21(CIP1/WAF1) participate in G1 cell cycle arrest in A. actinomycetemcomitans-infected J774.1 cells.


Critical appraisal of clinical judgment: an essential dimension of clinical ethics.
The morally responsible practice of clinical medicine depends on many factors, the integrity of clinical judgment chief among them. Responsible clinical judgment requires that it be deliberative. The disciplines of the humanities, all of which contribute to clinical ethics-as the papers that follow illustrate-teach that deliberative reasoning includes critical self-awareness and self-scrutiny. Critical appraisal proves essential to achieving both. The papers in the 2013 Clinical Ethics number of the Journal provide distinctive critical appraisals of clinical judgment: concepts of race; narrative; stewardship; and the Rule of Rescue. By becoming commonplace, such critical appraisals of clinical judgment become essential to clinical ethics.


Ultrasound-Guided Steroid Injection of the Pisotriquetral Joint: A Multidisciplinary Effort.
From the perspective of a multidisciplinary team, the authors describe the first reported use of ultrasound guidance for steroid injection into the pisotriquetral joint to relieve wrist pain of a person with spinal cord injury undergoing acute inpatient rehabilitation. Musculoskeletal ultrasound guidance was used to improve the accuracy of a corticosteroid injection of the pisotriquetral joint and the basal thumb in a 70-year-old man with paraplegia experiencing multifocal degenerative wrist pain. There was no bleeding or bruising after the injections, and the patient reported complete pain resolution 1 wk after the injections, which continued for over 1 yr. A multidisciplinary team was key in diagnosis, selection of treatment, and evaluation of treatment effect. Corticosteroid injection of the pisotriquetral joint under ultrasound guidance can be used as a treatment modality for managing wrist pain stemming from that joint. Further investigation and studies evaluating the use of ultrasound versus other imaging modalities for injection of the wrist are indicated.


Analysis of Mononuclear Phagocytes Disclosed the Establishment Processes of Two Macrophage Subsets in the Adult Murine Kidney.
The interstitium of kidney involves a variety of components including resident immune cells, in particular mononuclear phagocytes. However, many proposed markers for distinguishing macrophages or dendritic cells are, in fact, shared by the majority of renal mononuclear phagocytes, which impedes the research of kidney diseases. Here, by employing a flow cytometry strategy and techniques of fate mapping, imaging and lineage depletion, we were able to demarcate renal monocytes, macrophages and dendritic cells and their subsets in mice. In particular, using this strategy, we found that even in steady state, the renal macrophage pool was continuously replenished by bone marrow-derived monocytes in a stepwise process, i.e., from infiltration of classical monocyte, to development of nonclassical monocyte and eventually to differentiation to macrophages. In mechanism, we demonstrated that the ligation of tissue-anchored CX3CL1 and monocytic CX3CR1 was required for promoting monocyte differentiation to macrophages in the kidney, but CX3CL1-CX3CR1 signaling was dispensable in monocyte infiltrating into the kidney. In addition to the bone marrow-derived macrophages, fate mapping in adult mice revealed another population of renal resident macrophages which were embryo-derived and self-maintaining. Thus, the dissecting strategies developed by us would assist in exploration of the biology of renal mononuclear phagocytes.


Antithrombin, heparin, and heparan sulfate.
To review the experimental and clinical evidence that antithrombin has multiple mechanisms for both its anticoagulant and anti-inflammatory properties. The interaction between antithrombin and specific polysulfated, acidic oligosaccharide moieties found on heparin and related proteoglycan molecules within the circulation and on endothelial surfaces will also be examined. Review of the literature relating to antithrombin published during the past 25 yrs. Antithrombin is the most abundant endogenous anticoagulant circulating in human plasma. This serine protease inhibitor participates in the regulation of clotting in both physiologic and pathologic states. Reduced antithrombin activity in the early phases of sepsis contributes to a procoagulant state with excess activation of the innate immune response. Antithrombin binds to specific pentasaccharides expressed on heparin, glycosaminoglycans, and related proteoglycans within the circulation and along endothelial surfaces. The functions of neutrophils, monocytes, and endothelial cells are altered as a result of their interaction with antithrombin. These effects are mediated by the enzyme inhibitory action of antithrombin and its ability to function as a ligand for antithrombin receptors on cell surfaces. In addition, antithrombin exerts anti-inflammatory properties by both prostacyclin-dependent and prostacyclin-independent actions; heparin interferes with these anti-inflammatory properties. The role of antithrombin in sepsis, its therapeutic utility in severe sepsis, and its combination with heparin remain the subject of considerable debate. The results of a recent phase 3 clinical trials with high-dose antithrombin in sepsis suggested a beneficial effect in patients who did not concomitantly receive heparin, thereby generating new challenges in the understanding of interactions between antithrombin and heparin or heparin-like proteoglycans. Antithrombin has complex interactions with host coagulopathic and systemic inflammatory responses under physiologic conditions and in sepsis. The impact of these interactions in critically ill patients and the therapeutic implications of administration of antithrombin, and various doses and types of heparin in such patients, need further clarification.


Magnetic resonance imaging and spectroscopy of the brain in HIV disease.
Severe AIDS dementia complex is now a rare clinical condition in resource-rich settings in HIV-1-infected patients with access to modern antiretroviral therapies. However, minor neurocognitive decline and central nervous system abnormalities have been reported in clinical studies assessing HIV-1-infected subjects on modern antiretroviral therapy with undetectable plasma HIV-RNA. Ongoing characterisation and monitoring of these abnormalities are crucial to aid our understanding and assess future interventions. New magnetic resonance imaging (MRI) techniques, provide a non-invasive mechanism to assess impaired brain function (functional MRI, fMRI) and detect changes in brain biochemistry (magnetic resonance spectroscopy, MRS). In this review, changes described by fMRI and MRS in HIV disease both in the pre- and post-combination antiretroviral therapy eras are summarised.


Asymmetric Synthesis of Functionalized Tricyclic Chromanes via an Organocatalytic Triple Domino Reaction.
A highly stereoselective triple domino reaction for the synthesis of functionalized tricyclic chromane scaffolds has been developed. A secondary amine-catalyzed domino Michael/Michael/aldol condensation reaction between aliphatic aldehydes, nitro-chromenes, and α,β-unsaturated aldehydes leads to the formation of synthetically important tricyclic chromanes bearing four contiguous stereogenic centers including a tetrasubstituted carbon in good yields (20-66%) and excellent stereoselectivities (>20:1 dr and >99% ee).


Measurement of 8-arginine-vasopressin by radioimmunoassay. Development and application to urine and plasma samples using one extraction method.
This paper describes the production and evaluation of an antiserum with high affinity (Ka = 1.9 X 10(11) l/mol) and specifity to 8-arginine-vasopressin (AVP). The antiserum binds only to the intact and unchanged ring and tail of the AVP-molecule. AVP was labelled with 125I by a modification of the chloramin T method and purified by gel-filtration. We describe the development and validation of a radioimmunoassay for AVP in human plasma and urine, using only one extraction method (octa-decasilyl-treated silica microcolumns) for both biological fluids. The overall sensitivity of the assay method is 0.3 pg/ml plasma and 0.6 pg/ml urine. Mean (+/- SD) plasma AVP-concentration in normally hydrated females was 1.2 +/- 0.6 pg/ml (median 1.2 pg/ml) and 1.7 +/- 0.7 pg/ml (median 1.8 pg/ml) in males. Mean urinary AVP excretion was 73 +/- 43 ng/day with ad libitum water intake and normal activity. Sex differences were not statistically significant. We also assessed the response of plasma AVP and urinary AVP-excretion to waterload and dehydration.


Zelmac (Novartis AG).
Novartis is developing Zelmac (SDZ-HTF-919), a 5-HT4 receptor partial agonist, which is in phase III clinical trials for the treatment of gastric motility disorders and irritable bowel syndrome (IBS). Warburg Dillon Read estimated (in January 1999) that Zelmac will achieve sales of 240 million Swiss Francs in 2001.


An increased risk of epithelial ovarian cancer in Taiwanese women with a new surgico-pathological diagnosis of endometriosis.
Epidemiological evidence of relationships between endometriosis and epithelial ovarian cancer (EOC) has been obtained mainly from Western countries. Our goal was to determine the risk of EOC due to endometriosis in Taiwanese women. A retrospective cohort study was performed by linking to the National Health Insurance Research Database (NHIRD) of Taiwan. A total of 5,945 women with a new surgico-pathological diagnosis of endometriosis from 2000 to 2010 and 23,780 multivariable-matched controls (1:4) were selected. The Cox regression model adjusted for potential confounders was used to assess the risk of EOC due to endometriosis. The EOC incidence rate (IR) of the women with and without endometriosis was 11.64 and 2.66 per 10,000 person-years, contributing to a crude hazard ratio (HR) of 4.48 (95% confidence interval [CI] 2.84-7.06), and HR after adjustment for all confounders (adjusted HR) of 5.62 (95% CI 3.46-9.14); the risk was higher in clear-cell carcinoma subtypes (adjusted HR 7.36, 95% CI 1.91-28.33). The EOC IR of women with endometriosis consistently increased with increasing age, ranging from 4.99 (<30 years) to 35.81 (≥50 years) per 10,000 person-years, contributing to a progressively increased risk of EOC (crude HRs ranging from 2.80 to 6.74 and adjusted HRs ranging from 3.34 to 9.63) compared to age-matched women without endometriosis, whose EOC IR also increased with age. The older women (≥50 years) with endometriosis had a risk of EOC that was higher than both the age-matched women without endometriosis (adjusted HR 9.63, 95% CI 3.27-28.37) and the youngest women (<30 years) with endometriosis (adjusted HR 4.97, 95% CI 1.03-24.09). These significant findings corroborate the previously reported association between endometriosis and increased risk of EOC. Since the risk of EOC in women with a new surgico-pathological diagnosis of endometriosis constantly increased with age and this increased risk of EOC was more significant in women aged ≥50 years, active and intensive surgical intervention should be taken into consideration for older women with endometriosis.


Teaching Skill Acquisition and Development in Dental Education.
Development of dental faculty members is paramount to providing outstanding education and role modeling for students. With the large number of second career educators in dental schools, an efficient method of acquiring teaching skills is important for new faculty members. Knowing the skill progression and learning experiences identified by dental educators of varying rank may lead to more efficient, effective faculty development. The aims of this study were to identify the perceptions of a group of faculty members about the knowledge, skills, attitudes, and learning experiences that contribute to developing teaching expertise and to compare and contrast the perceptions of new and more senior faculty members on these subjects. The Dreyfus skill acquisition continuum of novice to expert performance was used as a construct reference. The study used a mixed-methods approach in which qualitative and quantitative data were collected concurrently in an electronic survey of faculty members at one U.S. dental school. Of the 492 total faculty members, 80 survey responses were received, for a 16% response rate. Open coding and analysis of responses revealed some common themes. Building rich content knowledge and learning varied methodologies for teaching and assessment, supported by an awareness of peer role models, were perceived to be features of early growth. Content prioritization, clarity, and customization appropriate for the learner characterized mid growth. As theorized in the Dreyfus model, more experienced faculty members described a fluid, less structured teaching process, increased reflection, and appreciation of the strength of the educational community. The results of this study may help increase dental educators' understanding of teaching skill acquisition and inform faculty development and support.


Molecular assessment of erythroid lineage chimerism following nonmyeloablative allogeneic stem cell transplantation.
Nonmyeloablative conditioning regimens for allogeneic stem cell transplantation are now commonly used in the treatment of patients with hematologic malignancies. Since this treatment often results in the establishment of mixed hematopoietic chimerism, this approach may also prove to be useful in the treatment of nonmalignant disorders, such as sickle cell disease and thalassemia major. To apply this approach to these diseases, it will be necessary to determine the levels of donor erythropoiesis required to correct hemolysis and ameliorate disease symptoms. Current methods for measuring hematopoietic chimerism are based on DNA polymorphisms that distinguish recipient from donor. These methods accurately measure donor leukocyte engraftment but do not quantify the relative contributions of recipient and donor erythropoiesis following transplant. To specifically measure erythroid-lineage chimerism, we used pyrosequencing of the sickle cell mutation to quantify the relative levels of normal and sickle beta-globin mRNA in patient samples. Results of beta-globin RNA chimerism were compared to assessment of beta-globin DNA chimerism as well as analysis of short tandem repeat (STR) polymorphisms, cytogenetics, and hemoglobin electrophoresis. Donor engraftment was measured in two adult patients following nonmyeloablative stem cell transplant for sickle cell disease. In Patient 1, 25 to 30% of peripheral leukocytes were donor derived after day 41. In contrast, more than 55% of peripheral blood beta-globin mRNA was of donor origin, and these results correlated with posttransplant clinical improvement. Patient 2 achieved 40 to 50% donor leukocyte engraftment from day 33 onward. This was associated with 70 to 100% peripheral blood donor beta-globin mRNA. These studies demonstrate that relatively low levels of donor leukocyte engraftment can be associated with higher levels of donor erythropoiesis and with significant clinical improvement. Pyrosequencing of lineage-specific mRNA directly measures functional reconstitution of donor cells and provides valuable information that can affect clinical decisions in patients with nonmalignant diseases following allogeneic transplant.


Prevalence, antibiotic profile, virulence determinants, ESBLs, and non-β-lactam encoding genes of MDR Proteus spp. isolated from infected dogs.
This study investigated the prevalence, antibiogram, virulence, extended-spectrum β-lactamases (ESBLs), and non-β-lactam encoding genes of Proteus species isolated from infected dogs in Ismailia province, Egypt. The study was conducted on 70 fecal swabs collected from dogs with diarrhea for bacteriological identification of Proteus spp. The positive isolates were evaluated for antibiotic susceptibility, molecular tests of virulence, ESBLs, and non-β-lactam encoding genes. Prevalence of Proteus spp. was 35.7% (25/70), including Proteus mirabilis (n = 23) and Proteus vulgaris (n = 2). The Proteus spp. prevalence revealed diversity, higher in males than females, in ages < 12 weeks. Investigation of antimicrobial resistance was found against penicillin and amoxicillin (100%), amoxicillin-clavulanic acid (32%), cephalosporins: cefotaxime and ceftazidime (36%), and monobactam: aztreonam (28%) as ESBLs, in addition to tetracycline (32%) and trimethoprim sulfamethoxazole (100%). The strains retrieved by PCR revealed ureC, zapA, and rsbA virulence genes with variant prevalence as 92%, 60%, and 52%, respectively. In addition, the recovered strains contained ESBL genes with a dramatic variable prevalence of 100%, 92%, 36%, and 32%, to bla TEM, bla SHV, bla CTX-M, and bla OXA-1, respectively, and non β-lactam encoding genes with a prevalence of 100%, 48%, 44%, 20%, and 12%, to sul1, tetA, intI1, qnrA, and aadA1. Moreover, 28% (7/25) of recovering strains were MDR (multidrug-resistant) up to four classes of antimicrobials, and 48% (12/25) of the examined strains were MDR up to three antimicrobial classes. In conclusion, to the best of our knowledge, our study could be the first report recording MDR Proteus spp. in dogs in Egypt.


Fungal community and cellulose-degrading genes in the composting process of Chinese medicinal herbal residues.
The fungal community and the population of 16S rRNA, 18S rRNA and cellulose-degrading genes during the 30-day composting process of Chinese medicinal herbal residues were investigated using Illumina MiSeq and quantitative real-time PCR. An obvious succession of fungal communities occurred during the composting process. Unidentified fungi predominated in the raw materials. As composting progressed, Ascomycota became the most dominant phylum, with Aspergillus being the most dominant genus, and Aspergillus fumigatus making up 99.65% of that genus. Because of the inoculation of cellulolytic fungi in the mature stage, the cellulose degradation rate in inoculation groups was faster and the relative abundances of Aspergillus and the glycoside hydrolase family 7 genes were significantly higher than those in the control groups. These indicated that the fungal inoculants facilitated the degradation of cellulose, increased cellulolytic fungi and optimized the community structure.


The immediate effect of the Honda Walking Assist Device on foot and ankle function in hemiplegic stroke patients.
[Purpose] We evaluated the reliability of the measurement function of the Honda Walking Assist Device and investigated the effect of the device on walking improvements, and foot and ankle function, in hemiplegic stroke patients. [Participants and Methods] We recruited 16 hemiplegic stroke patients who performed 10-meter walk tests, twice without assistance and once with device assistance. Based on the rate of change of velocity, we divided the participants into two groups and compared the walking parameters, the toe grip strength, the cross tests, and the maximum step width. Two examiners assessed the 10-meter walk test results, and the authors calculated the intraclass correlation coefficients for walking speed, stride length, cadence, flexion, extension, and scissor angles. [Results] The intraclass correlation coefficients were greater than 0.70 for all the walking parameters we measured. The device increased hip joint movement but did not alter the maximum walking speed of the stroke patients. The patients in the group with a greater change in velocity displayed lower toe grip strength and decreased maximum step width and used orthoses more commonly. [Conclusion] The walking measurement function of the device was reliable. The immediate effect of the device in stroke patients may be influenced by the level of paralysis and the presence of an orthosis.


Lnc-ing inflammation to disease.
Termed 'master gene regulators' long ncRNAs (lncRNAs) have emerged as the true vanguard of the 'noncoding revolution'. Functioning at a molecular level, in most if not all cellular processes, lncRNAs exert their effects systemically. Thus, it is not surprising that lncRNAs have emerged as important players in human pathophysiology. As our body's first line of defense upon infection or injury, inflammation has been implicated in the etiology of several human diseases. At the center of the acute inflammatory response, as well as several pathologies, is the pleiotropic transcription factor NF-κβ. In this review, we attempt to capture a summary of lncRNAs directly involved in regulating innate immunity at various arms of the NF-κβ pathway that have also been validated in human disease. We also highlight the fundamental concepts required as lncRNAs enter a new era of diagnostic and therapeutic significance.


Superior Electrocatalytic Activity of MoS2-Graphene as Superlattice.
Evidence by selected area diffraction patterns shows the successful preparation of large area (cm × cm) MoS2/graphene heterojunctions in coincidence of the MoS2 and graphene hexagons (superlattice). The electrodes of MoS2/graphene in superlattice configuration show improved catalytic activity for H2 and O2 evolution with smaller overpotential of +0.34 V for the overall water splitting when compared with analogous MoS2/graphene heterojunction with random stacking.


Intellectual maturity and longevity: late-blooming composers and writers live longer than child prodigies.
Life history theory links human physical and sexual development to longevity. However, there have been no studies on the association of intellectual development with longevity. This observational study investigates the relationship between the onset of intellectual maturity and lifespan through the life histories of composers and creative writers, whose intellectual development can be gauged through their compositions and writings. In these groups we model the relationship between the age at first creative work, and age at death using multilevel regression, adjusting for sex, date of birth, and nationality. Historical biographical records on 1110 musical composers and 1182 creative writers, born in the period 1400 AD through 1915 AD, were obtained from the Oxford Companion to Music and the Oxford Companion to English Literature. Composers and creative writers lived, respectively 0.16 (p = 0.02) and 0.18 (p < 0.01) years longer for each later year of age at first work. When completion of the first creative work is interpreted as a proxy for the onset of intellectual maturity in composers and creative writers, our findings indicate that a later onset of intellectual maturity is associated with higher longevity.


Production of a thermostable archaeal superoxide reductase in plant cells.
Pyrococcus furiosus superoxide reductase (SOR) is a thermostable archaeal enzyme that reduces superoxide without producing oxygen. When produced as a fusion protein with the green fluorescent protein in plant cells, P. furiosus SOR is located in the cytosol and nucleus. The recombinant SOR enzyme retains its function and heat stability when assayed in vitro. Importantly, expressing SOR in plant cells enhances their survival at high temperature indicating that it functions in vivo. The archaeal SOR provides a novel mechanism to reduce superoxide and demonstrates the potential for using archaeal genes to alter eukaryotic metabolism.


Recruitment of uterine NK cells: induction of CXC chemokine ligands 10 and 11 in human endometrium by estradiol and progesterone.
Uterine NK (uNK) cells express a unique set of markers compared with blood NK cells. However, recent studies suggest that uNK cells may be derived from the recruitment of blood NK cells into the endometrium. In this study, we used an in vitro organ culture system to demonstrate that estradiol induces expression of chemokines CXCL10 and/or CXCL11 within human endometrium in 85% of patient samples tested. The average increase in gene expression after 10(-9) M estradiol treatment was 8.5-fold for CXCL10 and 7.7-fold for CXCL11 compared with medium alone. We observed that a specific estrogen receptor antagonist (ICI182780) was able to prevent chemokine gene induction, indicating that the effect of estradiol was receptor mediated. Moreover, our study showed that progesterone induced CXCL10 and CXCL11 expression in 83% of endometrial samples tested. We have also found that uNK cells and blood NK cells express the receptor for CXCL10 and CXCL11, CXCR3, with the highest expression found on uNK cells and CD56(bright) blood NK cells. These data indicate that sex hormones induce specific chemokines in nonpregnant human endometrium that can activate NK cell migration, and suggest that this mechanism may account for the increased NK cell numbers in endometrium during the menstrual cycle.


Miscarriage and ectopic pregnancy 2: management.
This two-part unit explores miscarriage and ectopic pregnancy. This part, part 2, outlines diagnosis, management and key nursing interventions. It also discusses the emotional impact of pregnancy loss.


Mechanisms of vasopressin-induced intracellular Ca2+ oscillations in rat inner medullary collecting duct.
Arginine vasopressin (AVP) causes increase in intracellular Ca(2+) concentration with an oscillatory pattern. Ca(2+) mobilization is required for AVP-stimulated apical exocytosis in inner medullary collecting duct (IMCD). The mechanistic basis of these Ca(2+) oscillations was investigated by confocal fluorescence microscopy and flash photolysis of caged molecules in perfused IMCD. Photorelease of caged cAMP and direct activation of ryanodine receptors (RyRs) by photorelease of caged cyclic ADP-ribose (cADPR) both mimicked the AVP-induced Ca(2+) oscillations. Preincubation of IMCD with 100 μM 8-bromo-cADPR (a competitive inhibitor of cADPR) delayed the onset and attenuated the magnitude of AVP-induced Ca(2+) oscillations. These observations indicate that the cADPR/RyR pathway is capable of supporting Ca(2+) oscillations and endogenous cADPR plays a major role in the AVP-induced Ca(2+) oscillations in IMCD. In contrast, photorelease of caged inositol 1,4,5-trisphosphate (IP(3)) induced Ca(2+) release but did not maintain sustained Ca(2+) oscillations. Removal of extracellular Ca(2+) halted ongoing AVP-mediated Ca(2+) oscillation, suggesting that it requires extracellular Ca(2+) entry. AVP-induced Ca(2+) oscillation was unaffected by nifedipine. Intracellular Ca(2+) store depletion induced by 20 μM thapsigargin in Ca(2+)-free medium triggered store-operated Ca(2+) entry (SOCE) in IMCD, which was attenuated by 1 μM GdCl(3) and 50 μM SKF-96365. After incubation of IMCD with 1 nM AVP in Ca(2+)-free medium, application of extracellular Ca(2+) also triggered Ca(2+) influx, which was sensitive to GdCl(3) and SKF-96365. In summary, our observations are consistent with the notion that AVP-induced Ca(2+) oscillations in IMCD are mediated by the interplay of Ca(2+) release from RyRs and a Ca(2+) influx mechanism involving nonselective cation channels that resembles SOCE.


Leiomyosarcoma of gallbladder: a case report.
A case of leiomyosarcoma of gallbladder, a rare tumor in hepatobiliary region, is reported. The present case differs from previously reported cases in its presentation with empyema of gallbladder and multiple intrahepatic cholangiolytic abscesses. Curative surgery could not be undertaken on account of poor condition of patient, and invasion of tumor into liver and adjacent organs.


Student factors: understanding individual variation in college drinking.
Research on individual differences in drinking rates and associated problems among college students is reviewed. Studies are included if completed within U.S. college and university samples and found in published scientific literature as identified by several searches of national databases. The resulting review suggests first that the extant literature is large and varied in quality, as most studies use questionnaire responses from samples of convenience in cross-sectional designs. Evidence from studies of college samples does consistently suggest that alcohol is consumed for several different purposes for different psychological effects in different contexts. A pattern of impulsivity/sensation seeking is strongly related to increased drinking among students. This pattern is supported by research into personality, drinking motives, alcohol expectancies and drinking contexts. A second pattern of drinking associated with negative emotional states is also documented. Some long-term consequences of this second pattern have been described. Social processes appear especially important for drinking in many college venues and may contribute to individual differences in drinking more than enduring personality differences. Future research efforts should test interactive and mediating models of multiple risk factors and address developmental processes.


Peritumoral subarachnoid hemorrhage in microsurgical transitional interface type meningioma: may the interface play a role?
The evidence of an intracranial hemorrhage from a meningioma, in comparison with bleeding from different intracranial tumours, is very infrequent. The pathophysiological mechanisms that can explain the possibility of bleeding from meningiomas have not been yet completely clarified. We report a case of a left parasagittal meningotheliomatous meningioma, situated in the premotor cortex, presenting with a peritumoral hemorrhage, at the interface between the meningioma and the brain parenchyma, and strictly confined within the subarachnoid space. A detailed immunohystochemical study of the tumour was performed. The neuroradiological and neurosurgical analysis of the tumour-to-brain interface, served to understand the pathophysiology of this uncommon behaviour. Other possible pathomechanisms explaining bleeding from meningiomas, in the light of the more recent literature are discussed.


Synthesis of bisubstrate and donor analogues of sialyltransferase and their inhibitory activities.
[reaction: see text] Sialyltransferases (STs) are involved in the biosynthesis of glycoconjugates with important biological activities. Most STs utilize cytidine-5'-monophospho-N-acetylneuraminic acid (CMP-Neu5Ac) as a common donor substrate. A bisubstrate analogue containing the donor substrate (CMP-Neu5Ac mimic) and the acceptor substrate (galactose) was synthesized. Four donor analogues having the partial structure of the bisubstrate analogue were also synthesized to support study of the structure-activity relationship. Each analogue contains an ethylene group in place of the exocyclic anomeric oxygen of CMP-Neu5Ac. The bisubstrate analogue exhibited only weak inhibitory activity to rat recombinant alpha-2,3- and alpha-2,6-ST (IC(50) = 1.3, 2.4 mM). Conversion of the C-1 carboxylate of the Neu5Ac moiety to carboxyamide, hydroxymethyl, or methylene phosphate each resulted in a reduction in inhibitory activity. Among the synthesized analogues, cytidin-5'-yl sialylethylphosphonate (4) was the most potent inhibitor against rat recombinant alpha-2,3- and alpha-2,6-ST (IC(50) = 0.047, 0.34 mM).


Evaluation of Commonly Used Products for Disinfecting Clipper Blades in Veterinary Practices: A Pilot Study.
Nosocomial infections are a concern of growing interest in veterinary medicine. Clipper blades have been confirmed as fomites for numerous potential pathogens and, as such, may be associated with wound and surgical site infections. The goal of this study was to evaluate the disinfectant capabilities of several commonly used clipper blade cleaning products. Seventy sterile clipper blades were inoculated with strains of Pseudomonas aeruginosa , Escherichia coli , and Staphylococcus aureus . Blades were then subjected to one of seven treatment groups for disinfecting. Quantitative cultures of remaining bacteria were performed. All blades in the control group showed large amounts of bacterial recovery. Culture results showed no recovery in blades soaked in alcohol or chlorhexidine or those sprayed with an ethanol/o-phenylphenol product, while moderate recovery was seen with all other treatments. These results show that persistent contamination of clipper blades can occur with the use of several commonly used disinfectant products. Further research is necessary to evaluate fungicidal capabilities as well as the effect of disinfection on clipper blade maintenance.


Contributions of domesticated plant studies to our understanding of plant evolution.
Plant evolutionary theory has been greatly enriched by studies on crop species. Over the last century, important information has been generated on many aspects of population biology, speciation and polyploid genetics. Searches for quantitative trait loci (QTL) in crop species have uncovered numerous blocks of genes that have dramatic effects on adaptation, particularly during the domestication process. Many of these QTL have epistatic and pleiotropic effects making rapid evolutionary change possible. Most of the pioneering work on the molecular basis of self-incompatibility has been conducted on crop species, along with the sequencing of the phytopathogenic resistance genes (R genes) responsible for the 'gene-to-gene' relations of coevolution observed in host-pathogen relationships. Some of the better examples of co-adaptation and early acting inbreeding depression have also been elucidated in crops. Crop-wild progenitor interactions have provided rich opportunities to study the evolution of novel adaptations subsequent to hybridization. Most crop/wild F1 hybrids have reduced fitness, but in some instances the crop relatives have acquired genes that make them more efficient weeds through crop mimicry. Studies on autopolyploid alfalfa and potato have uncovered the means by which polyploid gametes are formed and have led to hypotheses about how multiallelic interactions are associated with fitness and self-fertility. Research on the cole crops and wheat has discovered that newly formed polyploids can undergo dramatic genome rearrangements that could lead to rapid evolutionary change. Many more important evolutionary discoveries are on the horizon, now that the whole genome sequence is available of the two major subspecies of rice Oryza sativa ssp. japonica and O. sativa ssp. indica. The rice sequence data can be used to study the origin of genes and gene families, track rates of sequence divergence over time, and provide hints about how genes evolve and generate products with novel biological properties. The rice sequence data has already been mined to show that transposable elements often carry fragments of cellular genes. This type of genome shuffling could play a role in creating novel, reorganized genes with new adaptive properties.


COVID-19 and sudden-onset ocular neurogenic palsy in prior healthy patients: a systematic review.
The aim of this systematic review is to identify cases of neurogenic ocular palsy in the presence of COVID-19 and to document patient characteristics, type of palsy and possible aetiologies. A systematic search of PubMed, Medline and CINAHL databases was conducted on the 6th of January 2023 to identify cases of neurogenic ocular palsy in patients with current or previous COVID-19 infection. Data were pooled to summarise the neurogenic palsy, patient clinical characteristics and proposed palsy mechanisms. The combined database search yielded 1197 articles. Of these, 23 publications consisting of 25 patients met the inclusion criteria. Most patients were male (68%) and ranged in age from 2 to 71 years (median=32.7, SD=21.4). Seven patients (28%) were children aged 2 to 10 years old. Abducens palsies were most common (68%) and the most common ocular presentation was diplopia (76%) with an average time of onset 15 days from testing positive to COVID-19 or having symptoms of the virus. Proposed mechanism of development of a neurogenic palsy secondary to COVID-19 infection was classified into one of three categories: vascular/thrombotic, a viral neuro-invasive or inflammatory virus-mediated immune response. This study suggests that COVID-19 infection may be linked to oculomotor, trochlear and abducens nerve palsies and the underlying mechanisms may vary but are difficult to definitively establish. Further studies investigating the onset of neurogenic palsy secondary to COVID-19 infection is required.


Effects of total glycosides from Baishouwu on human breast and prostate cancer cell proliferation.
Baishouwu (Cynanchum Auriculalum Royle ex Wight), a traditional Chinese herbal medicine, is used as a traditional anti-aging remedy in China. Previous studies suggested Baishouwu has multiple pharmacological actions. In this study, the total glycosides extracted from Baishouwu (CA/TG) were evaluated for its potential anti-tumor activity and mechanism on several human breast and prostate cancer cell lines. In [3H] thymidine incorporation assay. CA/TG inhibited the proliferation of cancer cells in a dose-dependent fashion. It also displayed anti-androgen activity on androgen sensitive cell line assessed by reporter gene assay. The morphological examination of CA/TG treated cells revealed overall shrinkage of nucleus, chromatin condensation and small nuclear fragments by DAPI staining, the characteristic pattern of DNA ladders were observed in cells exposed to CA/TG, indicating the involvement of apoptosis in its action. These results suggested that the CA/TG has preferred cytotoxicity against the cancer cells, and the action was due to its ability of preventing cell proliferation and inducing apoptosis.


The novel antioxidant, AC3056 (2,6-di-t-butyl-4-((dimethyl-4-methoxyphenylsilyl)methyloxy)phenol), reverses erectile dysfunction in diabetic rats and improves NO-mediated responses in penile tissue from diabetic men.
Diabetes is associated with a high incidence of erectile dysfunction (ED) and poor response to standard treatments. Oxidative stress could be relevant in the pathophysiology of diabetic ED. To evaluate the effects of the antioxidant, AC3056 (2,6-di-t-butyl-4-((dimethyl-4-methoxyphenylsilyl)methyloxy)phenol), on diabetic ED. Erectile responses to cavernosal nerve electrical stimulation were determined in streptozotocin-induced diabetic rats. Relaxation of human corpus cavernosal (HCC) tissue and penile resistance arteries (HPRA) from human cavernosal specimens was evaluated in organ chambers and myographs, respectively. The influence of AC3056 on erectile responses, lipid peroxidation, and nitrite plus nitrate serum content, and nuclear factor-kappaB (NF-kappaB) expression in penile tissue, in diabetic rats, and on endothelium-dependent and neurogenic relaxation of HCC and HPRA from diabetic patients was determined. Eight weeks of diabetes caused ED in rats that was prevented by oral AC3056 (0.3% w/w in rat chow) when given from the induction of diabetes. AC3056 also prevented the diabetes-induced elevation of serum thiobarbituric acid-reactive substances (TBARS), the reduction of serum nitric oxide (NO) derivatives, and the increase of NF-kappaB expression. Acute oral administration of AC3056 (450 mg/kg) partially reversed ED in 8-week diabetic rats. Complete reversion of ED was achieved after 3 days of treatment with 0.3% AC3056. This effect remained after 5 weeks of treatment, but it disappeared after withdrawing for 1 week. Erectile function in diabetic rats was inversely related to serum TBARS. AC3056- (30 microM) reversed endothelial dysfunction in diabetic HCC and enhanced endothelium-dependent relaxation in diabetic HPRA and significantly potentiated neurogenic relaxation of both tissues. The reduced cGMP content in HCC from diabetic patients after exposure to acetylcholine (10 microM) was corrected by AC3056 (30 microM). These results suggest that oxidative stress has a relevant role in pathophysiology of diabetic ED and provide a rationale for the use of antioxidant therapy in the treatment of ED in diabetes.


Microbiota characterization of sheep milk and its association with somatic cell count using 16s rRNA gene sequencing.
This work aimed to use 16S ribosomal RNA sequencing with the Illumina MiSeq platform to describe the milk microbiota from 50 healthy Assaf ewes. The global observed microbial community for clinically healthy milk samples analysed was complex and showed a vast diversity. The core microbiota of the sheep milk includes five genera: Staphylococcus, Lactobacillus, Corynebacterium, Streptococcus and Escherichia/Shigella. Although there are some differences, some of these genera are common with the microbiota core pattern of milk from other species, especially with dairy cows. The microbial composition of the studied samples, based on the definition of amplicon sequence variants, was analysed through a correlation network. A preliminary analysis by grouping the milk samples based on their somatic cell count (SCC), which is considered an indicator of subclinical mastitis (SM), showed certain differences for the core of the samples identified as SM. The differences in the microbiota diversity pattern among samples might also suggest that subclinical mastitis would be associated with the significant increase in some genera that are inhabitants of the mammary gland and a remarkable concomitant reduction in the microbial diversity. Additionally, we have also presented here a preliminary analysis to assess the impact of the sheep milk microbiome on SCC, as an indicator of subclinical mastitis. The results here reported provide a first characterization of the sheep milk microbiota and settle the basis for future studies in this field.


Atmospheric Pressure Plasma Deposition of Hybrid Nanocomposite Coatings Containing TiO2 and Carbon-Based Nanomaterials.
Among the different applications of TiO2, its use for the photocatalytic abatement of organic pollutants has been demonstrated particularly relevant. However, the wide band gap (3.2 eV), which requires UV irradiation for activation, and the fast electron-hole recombination rate of this n-type semiconductor limit its photocatalytic performance. A strategy to overcome these limitations relies on the realization of a nanocomposite that combines TiO2 nanoparticles with carbon-based nanomaterials, such as rGO (reduced graphene oxide) and fullerene (C60). On the other hand, the design and realization of coatings formed of such TiO2-based nanocomposite coatings are essential to make them suitable for their technological applications, including those in the environmental field. In this work, aerosol-assisted atmospheric pressure plasma deposition of nanocomposite coatings containing both TiO2 nanoparticles and carbon-based nanomaterials, as rGO or C60, in a siloxane matrix is reported. The chemical composition and morphology of the deposited films were investigated for the different types of prepared nanocomposites by means of FT-IR, FEG-SEM, and TEM analyses. The photocatalytic activity of the nanocomposite coatings was evaluated through monitoring the photodegradation of methylene blue (MB) as a model organic pollutant. Results demonstrate that the nanocomposite coatings embedding rGO or C60 show enhanced photocatalytic performance with respect to the TiO2 counterpart. In particular, TiO2/C60 nanocomposites allow to achieve 85% MB degradation upon 180 min of UV irradiation.


Cyclin C regulates adipogenesis by stimulating transcriptional activity of CCAAT/enhancer-binding protein α.
Brown adipose tissue is important for maintaining energy homeostasis and adaptive thermogenesis in rodents and humans. As disorders arising from dysregulated energy metabolism, such as obesity and metabolic diseases, have increased, so has interest in the molecular mechanisms of adipocyte biology. Using a functional screen, we identified cyclin C (CycC), a conserved subunit of the Mediator complex, as a novel regulator for brown adipocyte formation. siRNA-mediated CycC knockdown (KD) in brown preadipocytes impaired the early transcriptional program of differentiation, and genetic KO of CycC completely blocked the differentiation process. RNA sequencing analyses of CycC-KD revealed a critical role of CycC in activating genes co-regulated by peroxisome proliferator activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα). Overexpression of PPARγ2 or addition of the PPARγ ligand rosiglitazone rescued the defects in CycC-KO brown preadipocytes and efficiently activated the PPARγ-responsive promoters in both WT and CycC-KO cells, suggesting that CycC is not essential for PPARγ transcriptional activity. In contrast, CycC-KO significantly reduced C/EBPα-dependent gene expression. Unlike for PPARγ, overexpression of C/EBPα could not induce C/EBPα target gene expression in CycC-KO cells or rescue the CycC-KO defects in brown adipogenesis, suggesting that CycC is essential for C/EBPα-mediated gene activation. CycC physically interacted with C/EBPα, and this interaction was required for C/EBPα transactivation domain activity. Consistent with the role of C/EBPα in white adipogenesis, CycC-KD also inhibited differentiation of 3T3-L1 cells into white adipocytes. Together, these data indicate that CycC activates adipogenesis in part by stimulating the transcriptional activity of C/EBPα.


Animal models of arrhythmogenic right ventricular cardiomyopathy: what have we learned and where do we go? Insight for therapeutics.
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare genetically-determined cardiac heart muscle disorder characterized by fibro-fatty replacement of the myocardium that results in heart failure and sudden cardiac death (SCD), predominantly in young males. The disease is often caused by mutations in genes encoding proteins of the desmosomal complex, with a significant minority caused by mutations in non-desmosomal proteins. Existing treatment options are based on SCD prevention with the implantable cardioverter defibrillator, antiarrhythmic drugs, and anti-heart failure medication. Heart transplantation may also be required and there is currently no cure. Several genetically modified animal models have been developed to characterize the disease, assess its progression, and determine the influence of potential environmental factors. These models have also been very valuable for translational therapeutic approaches, to screen new treatment options that prevent and/or reverse the disease. Here, we review the available ARVC animal models reported to date, highlighting the most important pathophysiological findings and discussing the effect of treatments tested so far in this setting. We also describe gaps in our knowledge of the disease, with the goal of stimulating research and improving patient outcomes.


[On the history of the IVe Groupe: the institution of doubt, an aporia of training?].
The IVe Groupe was constituted through a common recognition of the dynamic virtue of the aporia of training. It serves to preserve a link, the necessity of which is intrinsic to the position of the psychoanalyst, with a psychoanalytic association. It envisages its "style" of organization as a part of training rather than envisaging its institution as a framework within which training takes place. It has thus historically maintained the Freudian advance within the problematics of temporality.


Effects of direct renin inhibition versus angiotensin II receptor blockade on angiotensin profiles in non-diabetic chronic kidney disease.
Direct renin inhibition (DRI) is clinically inferior to other blockers of the renin-angiotensin system (RAS). Thus far, the underlying molecular causes of this finding remain unknown. Twenty four patients with non-diabetic chronic kidney disease (CKD) stages III-IV and albuminuria were randomized to DRI or angiotensin receptor blocker (ARB). Employing a novel mass-spectrometry method, the concentrations of renin, aldosterone and plasma angiotensin peptides [Ang I, Ang II, Ang-(1-7), Ang-(1-5), Ang-(2-8), Ang-(3-8)] were quantified before and after an 8-week treatment. While blood pressure, renal function and albuminuria decreased comparably in both groups, profound RAS component differences were observed: DRI led to a massive renin increase, while suppressing both vasoconstrictive (Ang I and Ang II) and vasodilatory RAS metabolites (Ang-(1-7) and Ang-(1-5)). In contrast, ARB led to a four-fold increase of Ang I and Ang II, while Ang-(1-7) and Ang-(1-5) increased moderately but significantly. With ARB treatment, a decreased aldosterone-to-Ang II ratio suggested efficacy in blocking AT1 receptor. DRI therapy abolishes all RAS effector peptides. ARB increases both vasoconstrictive and vasodilative angiotensins, while this is accompanied by efficient blockade of vasoconstrictive effects. These differential molecular regulations should be considered when selecting optimal antihypertensive and disease-modifying therapy in CKD patients. Key messages Direct renin inhibition leads to a complete and lasting abolition of both classical and alternative RAS components. Angiotensin receptor blockade leads to effective receptor blockade and up-regulation of alternative RAS components. Differential molecular regulations of the RAS should be considered when selecting optimal antihypertensive and disease-modifying therapy in CKD patients.


Protein C and protein S activities in Behçet's disease as risk factors of thrombosis.
In Behçet's disease (BD), there is a marked increase in vascular complications. Approximately 30% of patients with BD suffer from thrombosis of the arteries and veins, varices, aneurysms, and thrombophlebitis of superficial or deep veins. Protein C and Protein S are major inhibitors of coagulation, and it is well known that the deficiency of Protein C and Protein S causes thrombotic disorders. Protein C and Protein S activities were measured in 23 patients with BD and in a control group consisting of 23 age- and sex-matched healthy volunteers. Patients who had received anticoagulant or oral contraceptive drugs, or who had liver disease or active thrombosis, were not included in the study. Of the 23 patients with BD (age, 13-55 years), the mean Protein S activities (94.2 +/- 11.3%) were slightly lower than the means of the control group (109.1 +/- 8.4%), but not statistically significant differences could be demonstrated (p > 0.05). Compared with the means of the control group (103.5 +/- 6.9%), the Protein C activities were not lower in BD (106.3 +/- 8.4%). No statistical difference was determined. Protein C and Protein S deficiencies are not a probable cause of thrombotic manifestations in BD. We do not recommend the measurement of these activities routinely in BD unless thrombosis is the major and primary manifestation of BD.


Multivalent, asymmetric IL-2-Fc fusions show enhanced selectivity for regulatory T cells.
The cytokine interleukin-2 (IL-2) has the potential to treat autoimmune disease but is limited by its modest specificity toward immunosuppressive regulatory T (Treg) cells. IL-2 receptors consist of combinations of α, β, and γ chains of variable affinity and cell specificity. Engineering IL-2 to treat autoimmunity has primarily focused on retaining binding to the relatively Treg-selective, high-affinity receptor while reducing binding to the less selective, low-affinity receptor. However, we found that refining the designs to focus on targeting the high-affinity receptor through avidity effects is key to optimizing Treg selectivity. We profiled the dynamics and dose dependency of signaling responses in primary human immune cells induced by engineered fusions composed of either wild-type IL-2 or mutant forms with altered affinity, valency, and fusion to the antibody Fc region for stability. Treg selectivity and signaling response variations were explained by a model of multivalent binding and dimer-enhanced avidity-a combined measure of the strength, number, and conformation of interaction sites-from which we designed tetravalent IL-2-Fc fusions that had greater Treg selectivity in culture than do current designs. Biasing avidity toward IL2Rα with an asymmetrical multivalent design consisting of one α/β chain-binding and one α chain-binding mutant further enhanced Treg selectivity. Comparative analysis revealed that IL2Rα was the optimal cell surface target for Treg selectivity, indicating that avidity for IL2Rα may be the optimal route to producing IL-2 variants that selectively target Tregs.


Indigenous Koro, a genital retraction syndrome of insular Southeast Asia: a critical review.
Koro, a disorder characterized by complaints of genital hyperinvolution and fear of impending death, is found to be indigenous to certain populations of insular Southeast Asia. Koro is similar to, but nevertheless distinct from, the Chinese syndrome which carries its name and serves as the transcultural prototype; the category of genital retraction syndromes is proposed as a substitute for the use of "koro" as the transcultural rubric. In a review of the Koro literature, an exploration of the many possible cultural and biomedical factors is begun; the issues and perspectives are relevant to the wider study of culture specific manifestations of genital retraction.


Evaluation of dabigatran for appropriateness of use and bleeding events in a community hospital setting.
Warfarin has been the predominant anticoagulant for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF). Its disadvantages are well-known and include a narrow therapeutic index, drug interactions, and the need for frequent monitoring. Dabigatran etexilate, a direct thrombin inhibitor, presents less complexity in prescribing and has emerged as an alternate therapy to warfarin. Although dabigatran does not require routine monitoring, concerns associated with its use include the lack of a reversal agent, complex dose adjustments, and limited guidance to the management of drug interactions. The goals of this study are to describe and to evaluate the use of dabigatran at a community hospital to identify areas for improvement in its prescribing. This retrospective chart review of patients at a community hospital in St Louis, MO, included patients who received at least 1 dose of dabigatran between December 2010 and June 2012. The appropriateness of dabigatran was evaluated based on recommendations approved by the US Food and Drug Administration for stroke prophylaxis in the setting of NVAF. The composite end point of bleeding included hospital readmission within 1 year of receiving at least 1 dose of dabigatran at the study institution secondary to bleeding, bleeding associated with a decrease in hemoglobin level by ≥2 g/dL or transfusion of ≥2 units of blood, or a notation of bleeding in the patient's medical record. Of the 458 patients included in the evaluation, 76 (16.6%) patients receiving dabigatran were using an inappropriate regimen of this drug, based on dose and frequency on the first day of therapy of dabigatran or the presence of valvular disease. Many patients (42.3%) received at least 1 dose of a concomitant parenteral anticoagulant. The composite end point for bleeding was reported in 66 (14.4%) patients, including 23 (5%) with confirmed gastrointestinal bleeding. High-risk medications such as dabigatran require monitoring of prescribing habits to improve patient safety and outcomes. Various initiatives, such as pharmacist interventions, therapeutic interchanges, and obtaining appropriate patient parameters, can be implemented in the practice setting to ensure the appropriate use of oral anticoagulants and improved patient outcomes.


High Water Resistance and Luminescent Thermal Stability of LiyNa(2-y)SiF6: Mn4+ Red-Emitting Phosphor Induced by Codoping of Li.
Mn4+-doped fluoride phosphors are efficient narrowband red-emitting phosphors for white light-emitting diodes (WLEDs) and backlight displays. However, erosion by moisture is the main obstacle that limits their application. In this work, LNSF:Mn4+ (Li0.06Na1.94Si0.94Mn0.06F6) with high quantum yield (QY), luminescent thermal stability, and waterproofness was synthesized using the H2O2-free reaction method at room temperature. Compared to NSF:Mn4+(Na2Mn0.06Si0.94F6), the QY value, luminescence thermal stability, and water resistance of LNSF:Mn4+ are obviously improved by codoping of Li+ because of the formation of charge-carrier transfer (CT) and rare-Mn4+ layer induced by codoping of Li+. The former produces the negative thermal quenching (NTQ) effect, which results in the improvement of the luminescent thermal stability. The latter can inhibit the hydrolysis of Mn4+ on the surface of the sample, which leads to the enhancement of waterproofness. The formation mechanism of the rare-Mn4+ layer is discussed. A prototype WLED emitting the ideal warm white light (CCT = 3173 K, Ra = 90.4) was assembled by coating a mixture of LNSF:Mn4+, yellow emitting phosphor (YAG:Ce3+), and epoxy resin on the blue light InGaN chip, indicating that the performance of the WLED can be improved by using LNSF:Mn4+.


Inhibitor coordination interactions in the binuclear manganese cluster of arginase.
Arginase is a manganese metalloenzyme that catalyzes the hydrolysis of L-arginine to form L-ornithine and urea. The structure and stability of the binuclear manganese cluster are critical for catalytic activity as it activates the catalytic nucleophile, metal-bridging hydroxide ion, and stabilizes the tetrahedral intermediate and its flanking states. Here, we report X-ray structures of a series of inhibitors bound to the active site of arginase, and each inhibitor exploits a different mode of coordination with the Mn(2+)(2) cluster. Specifically, we have studied the binding of fluoride ion (F(-); an uncompetitive inhibitor) and L-arginine, L-valine, dinor-N(omega)-hydroxy-L-arginine, descarboxy-nor-N(omega)-hydroxy-L-arginine, and dehydro-2(S)-amino-6-boronohexanoic acid. Some inhibitors, such as fluoride ion, dinor-N(omega)-hydroxy-L-arginine, and dehydro-2(S)-amino-6-boronohexanoic acid, cause the net addition of one ligand to the Mn(2+)(2) cluster. Other inhibitors, such as descarboxy-nor-N(omega)-hydroxy-L-arginine, simply displace the metal-bridging hydroxide ion of the native enzyme and do not cause any net change in the metal coordination polyhedra. The highest affinity inhibitors displace the metal-bridging hydroxide ion (and sometimes occupy a Mn(2+)(A) site found vacant in the native enzyme) and maintain a conserved array of hydrogen bonds with their alpha-amino and -carboxylate groups.


Effectiveness of nursing Intervention on anxiety, psychology and self-efficacy among elderly patients with acute coronary syndrome after percutaneous coronary intervention: An observational cohort study.
The aim of the present study is to investigate effect nursing intervention on anxiety, psychology and self-efficacy among elderly patients with acute coronary syndrome after percutaneous coronary intervention, and the correlation between patients' anxiety, psychology and self-efficacy and nursing intervention.One hundred thirty six patients with acute coronary intervention were randomly divided into the experimental group (n = 68) and the control group (n = 68). The experimental group received nursing intervention measures, and control group received routine nursing. We measured the depression, anxiety score of the 2 groups before and after nursing and multiple regressions was to analysis the correlation between patients' anxiety, psychology and self-efficacy and nursing intervention.The nursing intervention effect of the 2 groups after intervention were improved before intervention (P < .05), and the Hospital Anxiety and depression scale (HADS) in the was decreased than that of the control group after psychological intervention. The general self-efficacy scale scores of experimental group were obviously improved after receiving the intervention, and the scores in the experimental group were much higher than the control group after receiving the intervention, namely (P < .05). Furthermore, Single regression analysis showed that single (Marital status) (r = 0.367, P < .001), divorced or separated (Marital status) (r = 0.338, P < .001), Widowed (Marital status) (r = 0.458, P < .001), nursing intervention (r = 0.431, P < .001) and Length of hospital stay (r = 0.276, P = .003) showed a significant correlation with patients' anxiety, psychology and self-efficacy. Multiple regression analysis showed that Length of hospital stay (P = .001) and nursing intervention (P < .001) were significantly correlated with patients' anxiety, psychology and self-efficacy.Nursing intervention maybe significantly improve patients' anxiety, psychology and self-efficacy, and nursing intervention was significantly correlated with patients' anxiety, psychology and self-efficacy. Considering the limited number of studies analyzed, large sample-size clinical trials are necessary to verify the effect nursing intervention on anxiety, psychology and self-efficacy among elderly patients with acute coronary syndrome after percutaneous coronary intervention.


Local generation of hydrogen for enhanced photothermal therapy.
By delivering the concept of clean hydrogen energy and green catalysis to the biomedical field, engineering of hydrogen-generating nanomaterials for treatment of major diseases holds great promise. Leveraging virtue of versatile abilities of Pd hydride nanomaterials in high/stable hydrogen storage, self-catalytic hydrogenation, near-infrared (NIR) light absorption and photothermal conversion, here we utilize the cubic PdH0.2 nanocrystals for tumour-targeted and photoacoustic imaging (PAI)-guided hydrogenothermal therapy of cancer. The synthesized PdH0.2 nanocrystals have exhibited high intratumoural accumulation capability, clear NIR-controlled hydrogen release behaviours, NIR-enhanced self-catalysis bio-reductivity, high NIR-photothermal effect and PAI performance. With these unique properties of PdH0.2 nanocrystals, synergetic hydrogenothermal therapy with limited systematic toxicity has been achieved by tumour-targeted delivery and PAI-guided NIR-controlled release of bio-reductive hydrogen as well as generation of heat. This hydrogenothermal approach has presented a cancer-selective strategy for synergistic cancer treatment.


A smoking cessation intervention for rural veterans tailored to individual risk factors: A multicenter randomized clinical trial.
Rates of cigarette use remain elevated among those living in rural areas. Depressive symptoms, risky alcohol use, and weight concerns frequently accompany cigarette smoking and may adversely affect quitting. Whether treatment for tobacco use that simultaneously addresses these issues affects cessation outcomes is uncertain. The study was a multicenter, two-group, randomized controlled trial involving mostly rural veterans who smoke (N = 358) receiving treatment at one of five Veterans Affairs Medical Centers. The study randomly assigned participants to a tailored telephone counseling intervention or referral to their state tobacco quitline. Both groups received guideline-recommended smoking cessation pharmacotherapy, selected using a shared decision-making approach. The primary outcome was self-reported seven-day point prevalence abstinence (PPA) at three and six months. The study used salivary cotinine to verify self-reported quitting at six months. Self-reported PPA was significantly greater in participants assigned to Tailored Counseling at three (OR = 1.66; 95 % CI: 1.07-2.58) but not six (OR = 1.35; 95 % CI: 0.85-2.15) months. Post hoc subgroup analyses examining treatment group differences based on whether participants had a positive screen for elevated depressive symptoms, risky alcohol use, and/or concerns about weight gain indicated that the cessation benefit of Tailored Counseling at three months was limited to those with ≥1 accompanying concern (OR = 2.02, 95 % CI: 1.20-3.42). Biochemical verification suggested low rates of misreporting. A tailored smoking cessation intervention addressing concomitant risk factors enhanced short-term abstinence but did not significantly improve long-term quitting. Extending the duration of treatment may be necessary to sustain treatment effects.


Exposure to anticholinergic and sedative medication is associated with impaired functioning in older people with vertigo, dizziness and balance disorders-Results from the longitudinal multicenter study MobilE-TRA.
Introduction: Anticholinergic and sedative medication is prescribed for various conditions in older patients. While the general association between anticholinergic and sedative medication and impaired functioning is well established, its specific role in older individuals with vertigo, dizziness, and balance disorders (VDB) is still incompletely understood. The objective of this study was to investigate, whether an exposure to anticholinergic and sedative medication is associated with lower generic and lower vertigo-specific functioning in older patients with VDB. Methods: Data originates from the longitudinal multicenter study MobilE-TRA with two follow-ups, conducted from 2017 to 2019 in two German federal states. Exposure to anticholinergic and sedative medication was quantified using the drug burden index (DBI). Generic functioning was assessed by the Health Assessment Questionnaire Disability Index, appraising the amount of difficulties in performing activities of daily living (ADL). Vertigo-specific functioning was measured using the Vestibular Activities and Participation (VAP) questionnaire, assessing patient-reported functioning regarding activities of daily living that are difficult to perform because of their propensity to provoke VDB (Scale 1) as well as immediate consequences of VDB on activities and participation related to mobility (Scale 2). Longitudinal linear mixed models were applied to assess the association of exposure to anticholinergic and sedative medication at baseline and the level of generic and vertigo-specific functioning status over time. Results: An overall of 19 (7 from Bavaria) primary care physicians (mean age = 54 years, 29% female) recruited 158 (59% from Bavaria) patients with VDB (median age = 78 years, 70% female). Anticholinergic and sedative medication at baseline was present in 56 (35%) patients. An exposure to anticholinergic and sedative medication at baseline was significantly associated with lower generic functioning [Beta = 0.40, 95%-CI (0.18; 0.61)] and lower vertigo-specific functioning [VAP Scale 1: Beta = 2.47, 95%-CI (0.92; 4.02)], and VAP Scale 2: Beta = 3.74, 95%-CI [2.23; 5.24]). Conclusion: Our results highlight the importance of a close monitoring of anticholinergic and sedative medication use in older patients with VDB. When feasible, anticholinergic and sedative medication should be replaced by equivalent alternative therapies in order to potentially reduce the burden of VDB.


Smurf1 regulates tumor cell plasticity and motility through degradation of RhoA leading to localized inhibition of contractility.
Rho GTPases participate in various cellular processes, including normal and tumor cell migration. It has been reported that RhoA is targeted for degradation at the leading edge of migrating cells by the E3 ubiquitin ligase Smurf1, and that this is required for the formation of protrusions. We report that Smurf1-dependent RhoA degradation in tumor cells results in the down-regulation of Rho kinase (ROCK) activity and myosin light chain 2 (MLC2) phosphorylation at the cell periphery. The localized inhibition of contractile forces is necessary for the formation of lamellipodia and for tumor cell motility in 2D tissue culture assays. In 3D invasion assays, and in in vivo tumor cell migration, the inhibition of Smurf1 induces a mesenchymal-amoeboid-like transition that is associated with a more invasive phenotype. Our results suggest that Smurf1 is a pivotal regulator of tumor cell movement through its regulation of RhoA signaling.


Hypercalcemia in patients treated with CAPD.
The aim of this study was to examine the frequency of the occurence of hypercalcemia in patients treated with CAPD using solutions with the calcium concentration Ca 1.75 mmol/l and Ca 1.25 mmol/l. The study was performed on 11 patients treated with CAPD and lasted 48 weeks. The patients were treated with the calcium dialysate solutions Ca 1.75 mmol/l for 24 weeks. Then they swiched to Ca 1.25 mmol/l. The study was performed at the begining (0) after 2, 12 and 24 weeks of treatment with each kind of dialysate solutions. The measurements of only total calcium revealed three episodes of hypercalcemia--one in the 12th week and two in the 24th week. While the measurements of ionised calcium were performed we diagnosed 12 episodes of hypercalcemia. Four in each examined period--in the 2nd, 12th, 24th week. We did not observe the episodes of hypercalcemia during the treatment with the dialysate solution Ca 1.25 mmol/l.


Moisture-Resistant and Highly Selective NH3 Sensor Based on CdS/WS2 Composite Heterojunction.
This study reports the synthesis of CdS/WS2 composites via a green and ultra-low-cost hydrothermal method. By controlling the relative mass ratio between WS2 and CdS, an n-n type CdS/WS2 heterostructure, with excellent NH3 gas-sensitive properties, was developed and investigated at room temperature. Compared with pristine WS2 and CdS, the CdS/WS2-40%wt composite exhibited excellent selectivity of more than 4 orders of magnitude for sensing NH3, a very short recovery time of 3 s, and ultrahigh selectivity at room temperature. The large specific surface area of the CdS/WS2 composite increased the active sites for the gas-sensitive reaction. Additionally, the 2D morphology of CdS/WS2 and the heterojunction formed between WS2 and CdS contributed to the improved performance. Anti-humidity interference tests showed that the CdS/WS2 sample remained stable under real-time monitoring of NH3 at different ambient humidity values. This study paves the way for designing high-performance gas sensors operating at room temperature.


Mdm2 selectively suppresses DNA damage arising from inhibition of topoisomerase II independent of p53.
Mdm2 is often overexpressed in tumors that retain wild-type TP53 but may affect therapeutic response independently of p53. Herein is shown that tumor cells with MDM2 amplification are selectively resistant to treatment with topoisomerase II poisons but not other DNA damaging agents. Tumor cells that overexpress Mdm2 have reduced DNA double-strand breaks in response to doxorubicin or etoposide. This latter result is not due to altered drug uptake. The selective attenuation of DNA damage in response to these agents is dependent on both Mdm2 levels and an intact ubiquitin ligase function. These findings reveal a novel, p53-independent activity of Mdm2 and have important implications for the choice of chemotherapeutic agents in the treatment of Mdm2-overexpressing tumors.


Definitive evidence for hypoxic cells influencing cure in cancer therapy.
From an analysis of 2803 patients with carcinoma of the cervix treated by radiation therapy, a 62% cure rate can be shown. In those patients with Stage IIb and III disease, a haemoglobin level during treatment of below 12 g% was associated with a significantly higher pelvic recurrence rate, and also lower cure rate, than for those with a haemoglobin level 12g% or more. A prospective study shows that the correction of anaemia is associated with a decreased pelvic recurrence rate and an increased cure rate consistent with tumour hypoxia being greater in anaemic patients than in those with a normal haemoglobin level. It is also consistent with the thesis that hypoxia controls the radiation local control rate in patients with advanced carcinoma of the cervix.