Non-Small Cell Lung Cancers in Women and Men: Differences in Biology, Behavior, and Outcomes.
Lung cancer is the leading cause of cancer deaths in men and women, both because of its high incidence rates and poor prognosis without effective therapies. Environmental carcinogens, most predominantly tobacco smoke, play a significant role. There are continuously emerging data to suggest the biological process differs between lung cancers in men and women. Differences are seen in a variety of cellular pathways and responses to carcinogens and therapies. Particular note in this article is made of carcinogen processing by cytochrome P450s, estrogen receptor pathways, epidermal growth factor receptor mutations, and how these are not necessarily independent cellular processes. These topics are only very briefly summarized here and it was not possible to include many important references. The heterogeneity of lung cancers in men and women, as well as smokers and nonsmokers, are likely to become more apparent with further studies. Work previously done in our laboratory (EDRN, PIs David Chia & Lee Goodglick) served to further emphasize these differences. This report is dedicated to the memory of Lee Goodglick with whom I had the privilege to work for many years prior to his untimely death.


"Tell Me More About Your Child's Sleep": A Qualitative Investigation Of Sleep Problems In Children With ADHD.
To investigate parental experiences and perceptions of sleep problems in their children with Attention Deficit Hyperactivity Disorder (ADHD), the perceived impacts of sleep problems and coping strategies deployed by parents. Semi-structured interviews with twenty-six parents of pre-adolescent children with a diagnosis of ADHD, followed by thematic analysis of the interview transcripts. Three themes were generated from the data: Children's Sleep Difficulties; Impacts of Children's Sleep; and Improving Children's Sleep. Sleep initiation problems in children with ADHD were commonly reported by parents, were perceived to be linked in a bidirectional manner with executive and emotional problems, and were reported as being disruptive to parental sleep. Some parents reported that their children's sleep problems were the initial prompt that lead to a diagnosis of ADHD. Parents reported utilizing a range of coping strategies to mitigate sleep problems, such as controlling the bedroom sensory environment and using emotional "wind down" as part of the bedtime routine. Some parents endorsed a beneficial effect of melatonin on their children's sleep. Sleep problems in children with ADHD were perceived as important issues by parents. Equipping parents with evidence-based strategies for the management of their children's sleep may lead to benefits for the children, parents and wider household.


Class II MHC alleles in rheumatoid arthritis in Tamilnadu, India: is there an association?
Rheumatoid arthritis (RA) was reported to be associated with class II MHC alleles in different ethnic populations. A similar study was undertaken to determine the association of class II MHC with RA patients of Tamilnadu (Tamil-speaking Hindus), India. Thirty patients with RA and 39 healthy controls were included. Polymorphic second exons of the DRB1, DQA1, and DQB1 genes were amplified and subjected to SSOP typing. No allele was found to be significantly associated with RA. However DRB1*11 (P = 0.01) and DQB1*0302 (P = 0.02) were significantly associated with rheumatoid factor-positive RA patients. (All the DRB1*11-positive RA patients had either *04 or *10 allele as their second allele. This study is first of its kind in this population.


Multiplane loading of the extensor mechanism alters the patellar ligament force/quadriceps force ratio.
Since the direction of the quadriceps force and location of the patellofemoral contact point likely differ between axial and multiplane loadings, the force and moment balance solutions for a multiplane loading condition may not yield the same patella ligament force/quadriceps force ratio (F(PL)/F(Q) ratio) when compared with an axial loading condition. The purpose of this study was to compare the effects of an axial loading condition and an anatomical, multiplane loading condition on the F(PL)/F(Q) ratio at various knee flexion angles. Ten cadaver knees were used in this investigation. Each was mounted on a custom jig that was fixed to an Instron frame. Quadriceps muscle loads were applied with same resultant force magnitudes under two force directions, as follows: (1) axial loading (central quadriceps tendon loading parallel to the femoral axis), and (2) an anatomically based, multiplane loading condition (individual vasti loaded, taking into consideration physiologic muscle fiber orientation). Patellar ligament tension was measured using a buckle transducer. The patellar ligament force/quadriceps force ratio (F(PL)/F(Q) ratio) was calculated for both loading conditions at 0 deg, 20 deg, 40 deg, and 60 deg of knee flexion. Across the range of knee motion evaluated, the F(PL)/F(Q) ratio for the axial loading condition was significantly greater than the F(PL)/F(Q) ratio for the multiplane loading condition. Our results suggest that loading orientation affects the transfer of forces from the quadriceps tendon to the patellar ligament.


Limit of detection studies for application to natural product identification using high performance liquid chromatography coupled to nuclear magnetic resonance spectroscopy.
In the pursuit of new natural products, the demand to rapidly identify compounds present, in ever decreasing amounts, in complex crude extracts has become a limiting factor. Despite improvements in HPLC-NMR hardware and pulse sequences, no extensive limit of detection (LOD) investigations have been reported for the acquisition of 2D NMR spectroscopic experiments acquired through HPLC-NMR. In this study the LOD for five key 1D and 2D NMR spectroscopic experiments have been established, using two reference compounds, including the on-flow (WET 1D proton), stop-flow (WET1D proton), gCOSY, HSQCAD and gHMBCAD NMR experiments. The LOD for all of the NMR experiments were within the range of 700ng to 1mg for the set of fixed experimental parameters implemented. For principle components in a complex multi-component mixture, this would allow for in situ compound identification. HPLC-NMR analysis was employed to investigate the principle components present in a marine brown alga crude extract, Cystophora subfarcinata.


The "continuity visit" and the hospitalist model of care.
Previous analyses have focused on the importance of hospitalist-primary care physician communication to mitigate the harms of discontinuity when hospitalists care for inpatients. We believe that both patients and physicians may benefit if primary physicians visit patients (or at least speak directly to them) during hospitalizations when a hospitalist is the physician-of-record. We propose calling such encounters the "continuity visit" to emphasize that the visit is not purely "social." Moreover, we encourage research on the value of continuity visits and recommend compensation if research establishes that these visits improve the efficiency and quality of inpatient care or patient satisfaction and comfort.


Intrinsic properties of and thalamocortical inputs onto identified corticothalamic-VPM neurons.
Corticothalamic (CT) feedback plays an important role in regulating the sensory information that the cortex receives. Within the somatosensory cortex layer VI originates the feedback to the ventral posterior medial (VPM) nucleus of the thalamus, which in turn receives sensory information from the contralateral whiskers. We examined the physiology and morphology of CT neurons in rat somatosensory cortex, focusing on the physiological characteristics of the monosynaptic inputs that they receive from the thalamus. To identify CT neurons, rhodamine microspheres were injected into VPM and allowed to retrogradely transport to the soma of CT neurons. Thalamocortical slices were prepared at least 3 days post injection. Whole-cell recordings from labeled CT cells in layer VI demonstrated that they are regular spiking neurons and exhibit little spike frequency adaption. Two anatomical classes were identified based on their apical dendrites that either terminated by layer V (compact cells) or layer IV (elaborate cells). Thalamic inputs onto identified CT-VPM neurons demonstrated paired pulse depression over a wide frequency range (2-20 Hz). Stimulus trains also resulted in significant synaptic depression above 10 Hz. Our results suggest that thalamic inputs differentially impact CT-VPM neurons in layer VI. This characteristic may allow them to differentiate a wide range of stimulation frequencies which in turn further tune the feedback signals to the thalamus.


Migration ability and Toll-like receptor expression of human mesenchymal stem cells improves significantly after three-dimensional culture.
While the conventional two-dimensional (2D) culture protocol is well accepted for the culture of mesenchymal stem cells (MSCs), this method fails to recapitulate the in vivo native three-dimensional (3D) cellular microenvironment, and may result in phenotypic changes, and homing and migration capacity impairments. MSC preparation in 3D culture systems has been considered an attractive preparatory and delivery method recently. We seeded human umbilical cord-derived MSCs (hUCMSCs) in a 3D culture system with porcine acellular dermal matrix (PADM), and investigated the phenotypic changes, the expression changes of some important receptors, including Toll-like receptors (TLRs) and C-X-C chemokine receptor type 4 (CXCR4) when hUCMSCs were transferred from 2D to 3D systems, as well as the alterations in in vivo homing and migration potential. It was found that the percentage of CD105-positive cells decreased significantly, whereas that of CD34- and CD271-positive cells increased significantly in 3D culture, compared to that in 2D culture. The mRNA and protein expression levels of TLR2, TLR3, TLR4, TLR6, and CXCR4 in hUCMSCs were increased significantly upon culturing with PADM for 3 days, compared to the levels in 2D culture. The numbers of migratory 3D hUCMSCs in the heart, liver, spleen, and bone marrow were significantly greater than the numbers of 2D hUCMSCs, and the worst migration occurred in 3D + AMD3100 (CXCR4 antagonist) hUCMSCs. These results suggested that 3D culture of hUCMSCs with PADM could alter the phenotypic characteristics of hUCMSCs, increase their TLR and CXCR4 expression levels, and promote their migratory and homing capacity in which CXCR4 plays an important role.


Seminal plasma induces programmed cell death in cultured peripheral blood mononuclear cells.
Immunosuppressive properties of seminal plasma inhibit the recovery of infectious HIV from semen, and led to the view early in the pandemic that semen HIV was transmitted principally by infected semen cells. More recent studies have revealed significant titers of HIV RNA in seminal plasma, however, even from men receiving successful antiviral therapy. Thus, studies of infectious HIV in seminal plasma are important to understanding sexual transmission and response to therapy. The present studies were undertaken to determine whether seminal plasma immunosuppression is mediated by the induction of programmed cell death (PCD). Peripheral blood mononuclear cells (PBMCs) were cultured without or with phytohemagglutinin and seminal plasma from normal donors, or men postvasectomy, or seminal vesicle protein collected at surgery. PBMC survival was measured at 3, 6, and 18 hr of culture; cells were examined for evidence of PCD by uptake of the fluorescent dye YO-PRO, and for fragmented nuclear DNA by the TUNEL assay. Approximately 90% of PBMCs cultured with seminal plasma from intact or vasectomized men were lost during 18 hr of culture; seminal vesicle protein did not induce cell loss. PCD assays were positive for PBMCs exposed to the seminal plasma, and negative for PBMCs cultured with seminal vesicle protein. Serum was not required for PCD induction. A 3-hr pulse with seminal plasma was sufficient to initiate PCD. These findings indicate that PCD induction accounts for the cytotoxic properties of semen, that the PCD is not the result of semen amine oxidases, and either that substances produced by seminal vesicles only at ejaculation, or by the prostate, are responsible for PCD induction.


Defining and Estimating Healthy Aging in Spain: A Cross-sectional Study.
Using an operational continuum of healthy aging developed by U.S. researchers, we sought to estimate the prevalence of healthy aging among older Spaniards, inform the development of a definition of healthy aging in Spain, and foster cross-national research on healthy aging. The ELES pilot study is a nationwide, cross-sectional survey of community-dwelling Spaniards 50 years and older. The prevalence of healthy aging was calculated for the 65 and over population using varying definitions. To evaluate their validity, we examined the association of healthy aging with the 8 foot up & go test, quality of life scores and self-perceived health using multiple linear and logistic regression. The estimated prevalence of healthy aging varied across the operational continuum, from 4.5% to 49.2%. Prevalence figures were greater for men and those aged 65 to 79 years and were higher than in the United States. Predicted mean physical performance scores were similar for 3 of the 4 definitions, suggesting that stringent definitions of healthy aging offer little advantage over a more moderate one. Similar to U.S. researchers, we recommend a definition of healthy aging that incorporates measures of functional health and limiting disease as opposed to definitions requiring the absence of all disease in studies designed to assess the effect of policy initiatives on healthy aging.


Relationship between Estimated Glomerular Filtration Rate and Cardiovascular Mortality in a Japanese Cohort with Long-Term Follow-Up.
Patients with renal impairment are at risk of not only end-stage kidney disease but also cardiovascular disease (CVD). The current definition of CKD stage G3a is eGFR 45-59 ml/min/1.73 m2 and of G3b is 30-44 ml/min/1.73 m2, and subjects in the CKD 3a category are considered to be at lower risk of mortality than are those in CKD 3b. We evaluated the outcome of 97,043 people (33,131 men and 63,912 women) living in Ibaraki Prefecture who underwent annual community-based health checkups beginning in 1993 at age 40-80 years and who were followed for a mean of 17.1 years. The number of all-causes deaths was 20,534 (10,375 men and 10,159 women), of which 5,995 (2,695 men and 3,300 women) were deaths due to CVD. Multivariable-adjusted hazard ratio for CVD death in the eGFR 45-49 ml/min/1.73 m2 category was significantly increased (1.82; 95% confidential interval, 1.23-2.69) in non-elderly men, whereas all-cause mortality and CVD mortality in elderly men with eGFR 45-49 ml/min/1.73m2 were non significant. In contrast, both in non-elderly women and in elderly women with eGFR 45-49 ml/min/1.73 m2 showed small, but significant, increases in the risks of all-cause mortality and CVD. We demonstrated proportionate increases in mortality with decreasing eGFR in a Japanese CKD population. Like patients in the CKD G3b subgroup, non-elderly men and women with an eGFR of 45-49 ml/min/1.73 m2 (i.e. a part of CKD G3a) are at considerable risk of CVD mortality. Age dependent and eGFR dependent finer risk recognition were required for CVD prevention in clinical practice with regard to CKD patients.


Effects of soy milk ingestion immediately after resistance training on muscular-related biomarkers in older men: a randomized controlled trial.
We evaluated the effects of soy milk ingestion on changes in body composition, strength, power, and muscular-related biomarkers following 12 weeks of resistance training in older men. Thirty healthy older men (age = 65.63 ± 3.16 years; body mass = 62.63 ± 3.86 kg) were randomly assigned to one of two groups: soy milk + resistance training (SR) or placebo + resistance training (PR). Participants in the SR group received 240 ml of vanilla-flavoured non-dairy soy milk immediately after every training session and at the same time on non-training days. Differences in muscle mass, upper limb body strength (UBS), lower limb aerobic power (LAP), activin A, and GDF15 were significantly greater in the SR group vs. the PR group (P < 0.05). Both intervention groups experienced a significant (p < 0.05) reduction in body mass (PR = -3.9 kg; SR = -3.2 kg), body fat % (PR = -0.8%; SR = -1.2%), activin A (PR = -5.1 pg/ml; SR = -12.8 pg/ml), GDF15 (PR = -8.1 pg/ml; SR = -14.7 pg/ml), TGFβ1 (PR = -0.43 pg/ml; SR = -0.41 pg/ml), and increase in muscle mass (PR = 0.81 kg; SR = 2.5 kg), UBS (PR = 3.4 kg; SR = 6.7 kg), lower limb body strength (PR = 2.8 kg; SR = 5.2 kg), upper limb aerobic power (PR = 34.3 W; SR = 38.6 W), LAP (PR = 23.2 W; SR = 45.2 W), BDNF (PR = 8.3 ng/ml; SR = 12.7 ng/ml), and irisin (PR = 1.5 ng/ml; SR = 2.9 ng/ml) compared to baseline. The ingestion of soy milk during 12 weeks of resistance training augmented lean mass, strength, and power, and altered serum concentrations of skeletal muscle regulatory markers in older men.


Integrated network analysis and machine learning approach for the identification of key genes of triple-negative breast cancer.
Triple-negative breast cancer (TNBC) has attracted more attention compared with other breast cancer subtypes due to its aggressive nature, poor prognosis, and chemotherapy remains the mainstay of treatment with no other approved targeted therapy. Therefore, the study aimed to discover more promising therapeutic targets and investigating new insights of biological mechanism of TNBC. Six microarray data sets consisting of 463 non-TNBC and 405 TNBC samples were mined from Gene Expression Omnibus. The data sets were integrated by meta-analysis and identified 1075 differentially expressed genes. Protein-protein interaction network was constructed which consists of 486 nodes and 1932 edges, where 29 hub genes were obtained with high topological measures. Further, 16 features (hub genes), 12 upregulated (AURKB, CCNB2, CDC20, DDX18, EGFR, ENO1, MYC, NUP88, PLK1, PML, POLR2F, and SKP2) and four downregulated ( CCND1, GLI3, SKP1, and TGFB3) were selected through machine learning correlation based feature selection method on training data set. A naïve Bayes based classifier built using the expression profiles of 16 features (hub genes) accurately and reliably classify TNBC from non-TNBC samples in the validation test data set with a receiver operating curve of 0.93 to 0.98. Subsequently, Gene Ontology analysis revealed that the hub genes were enriched in mitotic cell cycle processes and Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that they were enriched in cell cycle pathways. Thus, the identified key hub genes and pathways highlighted in the study would enhance the understanding of molecular mechanism of TNBC which may serve as potential therapeutic target.


Phosphine substitution and linkage isomerization in cyclopentadienylruthenium bis(triphenylphosphine)thiocyanide and selenocyanide, CpRu(PPh3)2NCS and CpRu(PPh3)2SeCN.
The reaction between CpRu(PPh3)2NCS (1a) and PMePh2 yields CpRu(PPh3)(PMePh2)NCS (2a) while CpRu(PPh3)(PMePh2)Cl reacts with SCN- to form the S-bonded isomer, CpRu(PPh3)(PMePh2)SCN (2b). Compound 1a and the linkage isomers of 2 were characterized by X-ray crystallography. The kinetics of the reaction between 1a and PMePh2 under pseudo-first order conditions in THF and in fluorobenzene to form 2a are consistent with a dissociative interchange mechanism. Activation parameters for the reaction are: ΔH† = 15.7 ± 0.6 kcal mol-1 and ΔS† = -35 ± 2 cal mol-1 K-1 in THF vs. ΔH† = 24.8 ± 1.2 kcal mol-1 and ΔS† = -6 ± 4 cal mol-1 K-1 in C6H5F. In the presence of added SCN-, the rate of phosphine substitution is unchanged but a mixture of 2a and 2b is observed. The selenocyanate derivative, CpRu(PPh3)2SeCN (3b), crystallizes as the Se-bonded linkage isomer. Compound 3b reacts with PMePh2 under pseudo-first order conditions in fluorobenzene to form CpRu(PPh3)(PMePh2)SeCN (4b) at a much faster rate than 1a with activation parameters: ΔH† = 30.9 ± 4.8 kcal mol-1 and ΔS† = 22.4 ± 15.9 cal mol-1 K-1 with no evidence for linkage isomerization to the N-bonded products.


Imaging glioma extent with 131I-TM-601.
TM-601, a 36-amino-acid peptide, selectively binds to glioma cells but not normal brain parenchyma. A phase I/II clinical trial of intracavitary 131I-TM-601 in adult patients with recurrent high-grade glioma was performed to determine the biodistribution and toxicity of this potential therapy. We evaluated imaging and biodistribution data from this trial to assess whether 131I-TM-601 might be useful in determining tumor extent. Adult patients with recurrent high-grade gliomas underwent tumor resection, implantation of an intracavitary reservoir, and a single-dose injection of 370 MBq (10 mCi) 131I-TM-601 (0.25-1.0 mg of 131I-TM-601) 2-4 wks after surgery. Total-body planar scans and whole-brain SPECT scans were obtained on days 0, 1, 2, 3, and 6-8 after injection. Postresection MR images were coregistered to the SPECT scans using image analysis software. Analysis of the rate of radioactive decay and biologic elimination from the body and at the cavity site was performed. T1-weighted with gadolinium contrast (T1-Wc), T2-weighted (T2), and SPECT volumes were estimated by stereological Cavalieri sections and compared for overlap. Nonbound 131I-TM-601 was eliminated by 48 h after injection with the remaining radiolabeled peptide bound to tumor for at least 6-8 d. Biologic decay rates from 24 to 168 h after injection were only slightly shorter than the physical decay of 131I (6.3 vs. 8.0 d). A comparison of tumor volume estimates using all 3 imaging parameters indicated that 131I-TM-601-determined tumor volumes more closely paralleled T2 volumes than T1-Wc volumes. Overlap between coregistered MRI and SPECT scans corroborated the presence of radiolabeled peptide in the vicinity of infiltrating tumor up to 168 h after injection. 131I-TM-601 provides a reliable estimate for primary tumor extent. Further modification of this radiopeptide with other better imaging isotopes may provide an important tool for determining tumor extent and differentiating regions of viable tumor from necrosis.


Environmental Factors Impacting Bone-Relevant Chemokines.
Chemokines play an important role in normal bone physiology and the pathophysiology of many bone diseases. The recent increased focus on the individual roles of this class of proteins in the context of bone has shown that members of the two major chemokine subfamilies-CC and CXC-support or promote the formation of new bone and the remodeling of existing bone in response to a myriad of stimuli. These chemotactic molecules are crucial in orchestrating appropriate cellular homing, osteoblastogenesis, and osteoclastogenesis during normal bone repair. Bone healing is a complex cascade of carefully regulated processes, including inflammation, progenitor cell recruitment, differentiation, and remodeling. The extensive role of chemokines in these processes and the known links between environmental contaminants and chemokine expression/activity leaves ample opportunity for disruption of bone healing by environmental factors. However, despite increased clinical awareness, the potential impact of many of these environmental factors on bone-related chemokines is still ill defined. A great deal of focus has been placed on environmental exposure to various endocrine disruptors (bisphenol A, phthalate esters, etc.), volatile organic compounds, dioxins, and heavy metals, though mainly in other tissues. Awareness of the impact of other less well-studied bone toxicants, such as fluoride, mold and fungal toxins, asbestos, and chlorine, is also reviewed. In many cases, the literature on these toxins in osteogenic models is lacking. However, research focused on their effects in other tissues and cell lines provides clues for where future resources could be best utilized. This review aims to serve as a current and exhaustive resource detailing the known links between several classes of high-interest environmental pollutants and their interaction with the chemokines relevant to bone healing.


Tumor suppressive protein gene associated with retinoid-interferon-induced mortality (GRIM)-19 inhibits src-induced oncogenic transformation at multiple levels.
Interferons (IFNs) inhibit the growth of infectious pathogens and tumor development. Although IFNs are potent tumor suppressors, they modestly inhibit the growth of some human solid tumors. Their weak activity against such tumors is augmented by co-treatment with differentiation-inducing agents such as retinoids. Previous studies from our laboratory identified a novel gene product, gene associated with retinoid-interferon-induced mortality (GRIM)-19, as an IFN/all-trans retinoic acid-induced growth suppressor. However, the mechanisms of its growth suppressive actions are unclear. The src-family of tyrosine kinases is important regulators of various cell growth responses. Mutational activation of src causes cellular transformation by altering transcription and cytoskeletal properties. In this study, we show that GRIM-19 suppresses src-induced cellular transformation in vitro and in vivo by down-regulating the expression of a number of signal transducer and activator of transcription-3 (STAT3)-dependent cellular genes. In addition, GRIM-19 inhibited the src-induced cell motility and metastasis by suppressing the tyrosyl phosphorylation of focal adhesion kinase, paxillin, E-cadherin, and gamma-catenin. Effects of GRIM-19 on src-induced cellular transformation are reversible in the presence of specific short hairpin RNA, indicating its direct effect on transformation. GRIM-19-mediated inhibition of the src-induced tyrosyl phosphorylation of cellular proteins, such as focal adhesion kinase and paxillin, seems to occur independently of the STAT3 protein. GRIM-19 had no significant effect on the cellular transformation induced by other oncogenes such as myc and Ha-ras. Thus, GRIM-19 not only blocks src-induced gene expression through STAT3 but also the activation of cell adhesion molecules.


Interhemispheric transfer of predictive force control during grasping in cerebellar disorders.
When an object is repeatedly grasped and lifted, the balance between grip force (normal to the object's surface) and lift force (tangential to the object's surface) is programmed according to the mechanical object features within a few lifts. Information related to the mechanical object properties is easily transferred in between both hands, and the cerebellum may play an essential role for the integration and generalization of this information. Recently, we have shown that the transfer of weight-related information in between both hands is impaired in cerebellar degeneration (Nowak et al., Neuropsychologia, 43:20-27, 2005). Here, we investigated the role of the cerebellum for the inter-manual transfer of friction-related information. Healthy subjects and patients with either focal or generalized cerebellar disorders first repeatedly lifted an object with one hand followed by a series of lifts of the same object with the opposite hand. The experiments were performed with the object's grip surfaces covered with either silk or sandpaper. Patients and healthy subjects scaled grip force differentially to surface friction within a few lifts. However, the ability to transfer friction-related information from one hand to the other was disturbed in cerebellar patients. We interpret these data within the recent concept that the cerebellum is essential for the rapid integration and generalization of mechanical object features in between both hemispheres when handling objects in the environment.


Resilience and Associated Factors in Schizophrenia.
Resilience in schizophrenia has been associated with multiple clinical variables that, to the best of our knowledge, do not include impulsiveness, aggression and also personality and insight with possible influences, which remain as poorly investigated topics. This study investigated the relationships of resilience with depression, aggression, impulsivity, personality and insight in order to assess the factors that explain resilience in schizophrenia. The study included 139 individuals with clinically stable schizophrenia. Data were acquired by means of the Resilience Scale for Adults (RSA), the Positive and Negative Syndrome Scale (PANSS), the Calgary Depression Scale for Schizophrenia (CDSS), the Schedule for Assessment of Insight (SAI), the Eysenck Personality Questionnaire Revised-Abbreviated (EPQR-A), the Barratt Impulsiveness Scale, 11th version (BIS-11) and the Buss-Perry Aggression Questionnaire (BPAQ). Correlations of the scores of the RSA with the scores of the other psychometric scales and the demographic and clinical data were evaluated. Linear regression analysis was used to determine the factors predicting resilience. The PANSS total and general psychopathology scores and scale scores on depression, impulsiveness and aggression were negatively correlated with resilience scores. Attentional impulsiveness, neuroticism and depression predicted low levels of resilience. There were no significant correlations between insight and the total or subdimension scores of resilience except for the subdimension structural style. Treatments focusing only on clinical remission in schizophrenia are not sufficiently effective. Interventions for enhancing resilience in schizophrenia should consider depressive symptoms, attentional impulsivity and personality traits such as neuroticism.


PKA at a Cross-Road of Signaling Pathways Involved in the Regulation of Glioblastoma Migration and Invasion by the Neuropeptides VIP and PACAP.
Glioblastoma (GBM) remains an incurable disease, mainly due to the high migration and invasion potency of GBM cells inside the brain. PI3K/Akt, Sonic Hedgehog (SHH), and PKA pathways play major regulatory roles in the progression of GBM. The vasoactive intestinal peptide (VIP) family of neuropeptides and their receptors, referred in this article as the "VIP-receptor system", has been reported to regulate proliferation, differentiation, and migration in a number of tumor cell types and more particularly in GBM cells. These neuropeptides are potent activators of the cAMP/PKA pathway. The present study aimed to investigate the cross-talks between the above cited signaling cascades. Regulation by VIP-related neuropeptides of GBM migration and invasion was evaluated ex vivo in rat brain slices explanted in culture. Effects of different combinations of VIP-related neuropeptides and of pharmacological and siRNA inhibitors of PKA, Akt, and of the SHH/GLI1 pathways were tested on GBM migration rat C6 and human U87 GBM cell lines using the wound-healing technique. Quantification of nuclear GLI1, phospho-Akt, and phospho-PTEN was assessed by western-immunoblotting. The VIP-receptor system agonists VIP and PACAP-38 significantly reduced C6 cells invasion in the rat brain parenchyma ex vivo, and C6 and U87 migration in vitro. A VIP-receptor system antagonist, VIP10-28 increased C6 cell invasion in the rat brain parenchyma ex vivo, and C6 and migration in vitro. These effects on cell migration were abolished by selective inhibitors of the PI3K/Akt and of the SHH pathways. Furthermore, VIP and PACAP-38 reduced the expression of nuclear GLI1 while VIP10-28 increased this expression. Selective inhibitors of Akt and PKA abolished VIP, PACAP-38, and VIP10-28 effects on nuclear GLI1 expression in C6 cells. PACAP-38 induced a time-dependent inhibition of phospho-Akt expression and an increased phosphorylation of PTEN in C6 cells. All together, these data indicate that triggering the VIP-receptor system reduces migration and invasion in GBM cells through a PKA-dependent blockade of the PI3K/Akt and of the SHH/GLI1 pathways. Therefore, the VIP-receptor system displays anti-oncogenic properties in GBM cells and PKA is a central core in this process.


Video-assisted thoracic surgery lobectomy for stage I lung cancer.
The technique, safety, and oncologic efficacy of video-assisted thoracic surgery (VATS) lobectomy are controversial. Issues include operative time, lymph node yield, conversion to thoracotomy, resource utilization, recurrence, complications, and survival. From January 1995 to December 2001, 179 patients underwent VATS lobectomy for preoperative stage I lung cancer (T1N0, 118 patients; T2N0, 61 patients). Mean age was 64.34 years (range, 38 to 87); 91 were female and 88 were male. Contraindications to VATS lobectomy included any suggestion of hilar, endobronchial, or central lesions. Video-assisted thoracic surgery lobectomy was performed using three ports, partial anatomic hilar dissection, and mediastinal node dissection. Distribution of lobectomies was as follows: left upper lobe, 50 patients; left lower lobe, 27 patients; right upper lobe, 33 patients; right upper and right middle lobe, 29 patients; right middle lobe, 9 patients; right lower lobe, 30 patients; right middle lobe and right lower lobe, 1 patient. Mean operative time was 75 +/- 6 minutes. Mean lymph node yield was 11 +/- 5 nodes. Pathologic upstaging was noted in 14 of the 179 patients (7.8%). Mean hospitalization was 4.1 days (range, 2 days to 4 months). There were no conversions to thoracotomy and there was 1 death (1 of 179, 0.05%). Complications included air leak in 24 of 179 (13.4%), subcutaneous emphysema in 4 of 179 (2.2%), pneumonia in 10 of 179 (5.6%), wound infection in 5 of 179 (2.8%), respiratory failure in 3 of 179 (1.7%), pulmonary embolism in 2 of 179 (1.1%), and myocardial infarction in 1 of 179 (0.5%). At a mean follow-up of 37 months, local recurrence rate was 0.013 per person per year. Actuarial recurrence-free survival was 88% and 85% at 36 and 60 months respectively. For carefully selected patients VATS lobectomy for early stage lung cancer is a safe and effective strategy. Long-term follow-up is required to fully evaluate recurrence and survival.


Modulation of the effects of sotalol on Purkinje strand electromechanical characteristics.
The modulation of the effects of sotalol (30 microM) by two sodium channel blockers, tetrodotoxin (0.07 microM) and lidocaine (50 microM), and by a potassium channel activator, nicorandil (30 microM), were examined. Sotalol alone greatly increased Purkinje fiber transmembrane action potential duration and, in some preparations, induced early after depolarizations. Concurrent with the changes in action potential duration, sotalol also increased isolated Purkinje strand developed force paced at slow rates (0.33 Hz). These sotalol-induced alterations of Purkinje strand electromechanical characteristics were similar to those produced by either veratrine (0.6 or 1.0 micrograms/mL) or by tetraethylammonium (10 mM). The effects of sotalol on action potential duration and force development were reversed by exposure to either tetrodotoxin or nicorandil. Lidocaine also reversed the effects of sotalol on action potential duration and developed force. The sotalol-induced increase in action potential duration and development of early after depolarizations may, therefore, be abated by combination with drugs that either block cardiac sodium channels or that increase membrane potassium conductance. Combination with such drugs may help prevent the adverse arrhythmogenic effects of sotalol.


Knowledge structure and hotspots research of glioma immunotherapy: a bibliometric analysis.
Glioma is the most common primary brain tumor. Traditional treatments for glioma include surgical resection, radiotherapy, chemotherapy, and bevacizumab therapy, but their efficacies are limited. Immunotherapy provides a new direction for glioma treatment. This study aimed to summarize the knowledge structure and research hotspots of glioma immunotherapy through a bibliometric analysis. Publications pertaining to glioma immunotherapy published during the period from 1st January 1990 to 27th March 2023 were downloaded from the Web of Science Core Collection (WoSCC). Bibliometric analysis and visualization were performed using the CiteSpace, VOSviewer, Online Analysis Platform of Literature Metrology, and R software. The hotspots and prospects of glioma immunotherapy research were illustrated via analyzing the countries, institutions, journals, authors, citations and keywords of eligible publications. A total of 1,929 publications pertaining to glioma immunotherapy in 502 journals were identified as of 27th March 2023, involving 9,505 authors from 1,988 institutions in 62 countries. Among them were 1,285 articles and 644 reviews. Most of publications were produced by the United States. JOURNAL OF NEURO-ONCOLOGY published the majority of publications pertaining to glioma immunotherapy. Among the authors, Lim M contributed the largest number of publications. Through analyzing keyword bursts and co-cited references, immune-checkpoint inhibitors (ICIs) were identified as the research focus and hotspot. Using a bibliometric analysis, this study provided the knowledge structure and research hotspots in glioma immunotherapy research during the past 33 years, with ICIs staying in the current and future hotspot. Our findings may direct the research of glioma immunotherapy in the future.


Dynamic regulation of Src-family kinases by CD45 in B cells.
CD45 is a key protein tyrosine phosphatase regulating Src-family protein tyrosine kinases (Src-PTKs) in lymphocytes; precisely how it exerts its effect remains controversial, however. We previously demonstrated that CD45 negatively regulates Lyn in the WEHI-231 B-cell line. Here we show that negative regulation by CD45 is physiologically significant in B cells and that some CD45 is constitutively associated with glycolipid-enriched microdomains (GEMs), where it inhibits Src-PTKs by dephosphorylating both the negative and the positive regulatory sites. Upon B-cell receptor (BCR) ligation, however, CD45 dissociates from GEMs within 30 seconds, inducing phosphorylation of 2 regulatory sites and activation of Src-PTKs, but subsequently reassociates with the GEMs within 15 minutes. Disruption of GEMs with methyl-beta-cyclodextrin results in abrogation of BCR-induced apoptosis in WEHI-231 cells, suggesting GEMs are critical to signals leading to the fate determination. We propose that the primary function of CD45 is inhibition of Src-PTKs and that the level of Src-PTK activation and the B-cell fate are determined in part by dynamic behavior of CD45 with respect to GEMs.


Constructing tunable coordinatively unsaturated sites in Fe-based metal-organic framework for effective degradation of pharmaceuticals in water: Performance and mechanism.
Micropollutants are ubiquitously detected in the aqueous environment, which needs to be removed by novel materials effectively. Herein, we synthesized a photo-Fenton catalyst based on MIL-53 (Fe) to effectively degrade sulfadimidine, one of the micropollutants in water. Abundant Lewis acid active sites (54.26 μmol/g) were successfully constructed within the metal cluster using FeCl3·6H2O, 1,4-benzene dicarboxylate, and modulators. This study reports a strategy by effectively constructing tunable Lewis acid active sites within the cavities in MIL-53 (Fe) via a facile solvothermal reaction for sixteen micropollutants removal. The photo-Fenton degradation of sulfamethazine was completely removed (∼99%) within only 1 min with a small amount of hydrogen peroxide added. Both theoretical calculation and the experiment results prove that introducing the unsaturated coordinated/lewis acid sites can remarkably reduce the band gap energy and increase the charge-separation efficiency by changing the electron configuration with more distribution asymmetry of structures. The effective degradation of structurally diverse pharmaceuticals with environmentally relevant concentrations was studied by immobilizing MOF-catalyst into a PVDF support. This work advanced the development of effective approaches for emergency contaminants control.


VirusCircBase: a database of virus circular RNAs.
Circular RNAs (circRNAs) are covalently closed long noncoding RNAs critical in diverse cellular activities and multiple human diseases. Several cancer-related viral circRNAs have been identified in double-stranded DNA viruses (dsDNA), yet no systematic study about the viral circRNAs has been reported. Herein, we have performed a systematic survey of 11 924 circRNAs from 23 viral species by computational prediction of viral circRNAs from viral-infection-related RNA sequencing data. Besides the dsDNA viruses, our study has also revealed lots of circRNAs in single-stranded RNA viruses and retro-transcribing viruses, such as the Zika virus, the Influenza A virus, the Zaire ebolavirus, and the Human immunodeficiency virus 1. Most viral circRNAs had reverse complementary sequences or repeated sequences at the flanking sequences of the back-splice sites. Most viral circRNAs only expressed in a specific cell line or tissue in a specific species. Functional enrichment analysis indicated that the viral circRNAs from dsDNA viruses were involved in KEGG pathways associated with cancer. All viral circRNAs presented in the current study were stored and organized in VirusCircBase, which is freely available at http://www.computationalbiology.cn/ViruscircBase/home.html and is the first virus circRNA database. VirusCircBase forms the fundamental atlas for the further exploration and investigation of viral circRNAs in the context of public health.


Son and father.
I have traced in my deliberations the mutual influence of drive and ego development throughout the male child's dyadic and triadic father relatedness as it proceeds within a changing soma and social surround during the first two decades of life. I have made the effort to conceptualize the normal developmental progression in male personality formation with explicit reference to the fate of the boy's dyadic father relationship as well as his negative Oedipus complex in general. These considerations, restricted as they are in scope and gender, assign to the dyadic father complex a nuclear role in neurosogenesis as well as recognize in it an etiological factor in relation to specific forms of psychopathology throughout the male life cycle.


In child and adult migraineurs the somatosensory cortex stands out … again: An arterial spin labeling investigation.
Over the past decade, human brain imaging investigations have reported altered regional cerebral blood flow (rCBF) in the interictal phase of migraine. However, there have been conflicting findings across different investigations, making the use of perfusion imaging in migraine pathophysiology more difficult to define. These inconsistencies may reflect technical constraints with traditional perfusion imaging methods such as single-photon emission computed tomography and positron emission tomography. Comparatively, pseudocontinuous arterial spin labeling (pCASL) is a recently developed magnetic resonance imaging technique that is noninvasive and offers superior spatial resolution and increased sensitivity. Using pCASL, we have previously shown increased rCBF within the primary somatosensory cortex (S1) in adult migraineurs, where blood flow was positively associated with migraine frequency. Whether these observations are present in pediatric and young adult populations remains unknown. This is an important question given the age-related variants of migraine prevalence, symptomology, and treatments. In this investigation, we used pCASL to quantitatively compare and contrast blood flow within S1 in pediatric and young adult migraineurs as compared with healthy controls. In migraine patients, we found significant resting rCBF increases within bilateral S1 as compared with healthy controls. Furthermore, within the right S1, we report a positive correlation between blood flow value with migraine attack frequency and cutaneous allodynia symptom profile. Our results reveal that pediatric and young adult migraineurs exhibit analogous rCBF changes with adult migraineurs, further supporting the possibility that these alterations within S1 are a consequence of repeated migraine attacks. Hum Brain Mapp 38:4078-4087, 2017. © 2017 Wiley Periodicals, Inc.


A prospective randomized comparison of type of nephrostomy drainage following percutaneous nephrostolithotomy: large bore versus small bore versus tubeless.
We compared postoperative outcomes among tubeless, conventional large bore nephrostomy drainage and small bore nephrostomy drainage following percutaneous nephrostolithotomy (PCNL) in a prospective randomized fashion. Between January and June 2001, 30 patients undergoing PCNL were randomized to receive conventional large bore (20Fr) nephrostomy drainage (group 1, 10 patients), small bore (9Fr) nephrostomy drainage (group 2, 10 patients) or no nephrostomy drainage (group 3, 10 patients). Inclusion criteria included a single subcostal tract, uncomplicated procedure, normal preoperative renal function and complete stone clearance. Factors compared among the 3 groups were postoperative analgesia requirement, urinary extravasation, duration of hematuria, duration of urinary leak, decrease in hematocrit and hospital stay. The postoperative analgesic requirement was significantly higher in group 1 (217 mg) compared to groups 2 (140 mg, p <0.05) and 3 (87.5 mg, p <0.0001). Patients in group 3 had a significantly shorter duration (4.8 hours) of urinary leak through the percutaneous renal tract compared to patients in groups 1 (21.4 hours, p <0.05) and 2 (13.2 hours, p <0.05). Hospital stay was significantly shorter in group 3 (3.4 days) compared to groups 1 (4.4 days, p <0.05) and 2 (4.3 days, p <0.05). All 3 groups were similar in terms of operative time, duration of hematuria and decrease in hematocrit. Postoperative ultrasound did not reveal significant urinary extravasation in any case. Tubeless PCNL is associated with the least postoperative pain, urinary leakage and hospital stay. Small bore nephrostomy drainage may be a reasonable option in patients in whom the incidence of stent dysuria is likely to be higher.


Optical configuration of a horizontal-switching liquid-crystal cell for improvement of the viewing angle.
We propose an optical configuration of a horizontal-switching liquid-crystal cell, consisting of a splayed liquid-crystal cell and uniaxial films, to improve the viewing angle characteristics by compensating for the phase dispersion in a diagonal direction. The optical design of the proposed configuration was performed on a Poincaré sphere with geometric calculations. By fabricating in-plane switching cells with the introduced configuration, we demonstrated their optical performances. As a result, we found that the diagonal viewing angle of the proposed horizontal-switching cell could be increased by 80% compared to a symmetrical viewing cone.


Aromaticity and amyloid formation: effect of π-electron distribution and aryl substituent geometry on the self-assembly of peptides derived from hIAPP(22-29).
A comprehensive investigation of peptides derived from the 22-29 region of human islet amyloid polypeptide (hIAPP) that contain phenylalanine analogs at position 23 with a variety of electron donating and withdrawing groups, along with heteroaromatic surrogates, has been employed to interrogate how π-electron distribution effects amyloid formation. Kinetic aggregation studies using turbidity measurements indicate that electron rich aromatic ring systems consistently abolish the amyloidogenic propensity of hIAPP(22-29). Electron poor systems modulate the rate of aggregation. Raman and Fourier transform infrared spectroscopy confirm the parallel β-sheet secondary structure of aggregates derived from peptides containing electron poor phenylalanine analogs and provide direct evidence of ring stacking. Transmission electron microscopy confirms the presence of amyloid fibrils. The effect of aryl substituent geometry on peptide self-assembly reveals that the electronic nature of substituents and not their steric profile is responsible for failure of the electron donating group peptides to aggregate. Non-aggregating hIAPP(22-29) peptides were found to inhibit the self-assembly of full-length hIAPP(1-37). The most potent inhibitory peptides contain phenylalanine with the p-amino and p-formamido functionalities. These novel peptides may serve as leads for the development of future aggregation inhibitors. A potential mechanism for inhibition of amylin self-assembly by electron rich (-29) peptides is proposed.


MicroRNA‑20 induces methylation of hepatitis B virus covalently closed circular DNA in human hepatoma cells.
Methylation was suggested to suppress the transcriptional activity of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) in hepatocytes. This may be associated with its low replicative activity during the inactive stage of chronic HBV infection; however, the exact mechanisms of methylation in HBV infection remain unknown. We have previously shown that short hairpin RNAs induced the methylation of the HBV genome in hepatoma cell lines. We also reported that the microRNA (miR) 17‑92 cluster negatively regulates HBV replication in human hepatoma cells. In addition, miR‑20a, a member of the miR 17‑92 cluster, has sequence homology with the short hairpin RNA that induces HBV methylation. In the present study, we investigated whether miR‑20a can function as an endogenous effector of HBV DNA methylation. The results indicated that overexpression of miR‑20a could suppress the replicative activity of HBV and increased the degree of methylation of HBV cccDNA in the HepAD38 hepatoma cell line. Argonaute (AGO)1 and AGO2, effectors of the RNA‑induced silencing complex, were detected in the nucleus of HepAD38 cells; however, only AGO2 was bound to HBV cccDNA. In addition, intranuclear AGO2 was determined to be bound with miR‑20a. In conclusion, miR‑20a may be loaded onto AGO2, prior to its translocation into the nucleus, inducing the methylation of HBV DNA in human hepatoma cells, leading to the suppression of HBV replication.


Establishing the criterion validity of self-report measures of adherence in hemodialysis through associations with clinical biomarkers: A systematic review and meta-analysis.
Accurate measurement of adherence is crucial to rigorously evaluate interventions aimed at improving this outcome in patients undergoing in-center hemodialysis. Previous research has shown great variability in non-adherence rates between studies, mainly due to the use of different direct (e.g., clinical biomarkers) and indirect (e.g., questionnaires) measures. Although self-reported adherence in hemodialysis has been widely explored, it is still unclear which is the most accurate questionnaire to assess this outcome; therefore, the question of how to optimize adherence measurement in research and clinical practice has emerged as a key issue that needs to be addressed. This systematic review and meta-analysis aimed to explore the criterion validity of self-report measures of adherence in hemodialysis established through the association between test scores and clinical biomarkers (the criterion measure). The protocol was registered in PROSPERO (2021 CRD42021267550). The last search was performed on March 29th, 2022, on Web of Science (all databases included), Scopus, CINHAL, APA PsycInfo, and MEDLINE/PubMed. Twenty-nine primary studies were included, and thirty-eight associations were analyzed. The Hunter-Schmidt's meta-analysis was computed for the associations with more than two studies (n = 20). The results showed that six associations were large (16%), 11 were medium (29%) and the remaining were of small strength. The test scores from the End-Stage Renal Disease Adherence Questionnaire (range: 0.212<rc <0.319) and the Dialysis Diet and Fluid Non-Adherence Questionnaire (range: 0.206<rc <0.359) had medium to large strength associations with interdialytic weight gain, serum phosphorus, and potassium levels, indicating that these questionnaires have reasonable concurrent criterion validity to measure fluid control and adherence to dietary restrictions in patients receiving hemodialysis. The available data did not allow exploring the criterion validity of the test scores in relation to hemodialysis attendance (skipping and/or shortening sessions). These results suggest that the decision to use one questionnaire over another must be made with caution, as researchers need to consider the characteristics of the sample and the objectives of the study. Given that direct and indirect methods have their advantages and disadvantages, the combination of adherence measures in hemodialysis is recommended to accurately assess this complex and multidimensional outcome.


Integration between abutting retinas: role of glial structures and associated molecules at the interface.
Integration between subretinal grafts and the host retina is limited in part by the presence of a barrier at the graft-host interface. This study was conducted to identify factors that may contribute to this barrier, by examining the distribution of glial structures and associated molecules in different setups of overlapping retinal pieces. Neuroretinal tissue derived from mice that express green fluorescent protein (GFP) was fragmented and transplanted into the subretinal space of adult rd1 mice. In an in vitro system, two retinal pieces, derived from GFP and rd1 mice, respectively, were placed overlapping each other and forming either laminar-laminar pairs or fragment-laminar pairs. The glia-associated markers analyzed included glial fibrillary acidic protein (GFAP), cellular retinaldehyde-binding protein (CRALBP), and two molecules known to inhibit neurite outgrowth: CD44 and neurocan. Bridging fibers and migrated cells were visualized with GFP fluorescence and retinal cell markers. A thick CRALBP-immunolabeled band was observed in the interface in cultured laminar-laminar pairs, whereas a thinner band was seen in cultured fragment-laminar pairs and in transplants. Accumulation of CD44 and neurocan was also observed in the interface between abutting retinal pieces in all setups. GFP(+) bridging fibers and GFP(+) cells (some of which coexpressed neuronal markers) were observed within the abutting rd1 retina in some areas. However, such integration occurred exclusively where CRALBP, CD44, and neurocan immunolabeling appeared disrupted in the interface, but coincided with high GFAP expression within the rd1 retina. The results demonstrate that, on the one hand, an accumulation of glial-associated inhibitory molecules in the interface correlates with limited integration between overlapping retinal pieces. On the other hand, glial reactivity within the rd1 retina does not appear to be incompatible with integration.


Pulsed light treatment enhances starch hydrolysis and improves starch physicochemical properties of germinated brown rice.
Recently, germinated brown rice (GBR) has gained substantial attention as a functional food because of its nutritional attributes. Notably, pulsed light technology (PLT) has emerged as a promising tool for enhancing rice germination and, consequently, has improved the nutritional and functional qualities of GBR-derived products. However, further research is required to comprehensively understand the impact of PLT on GBR physicochemical properties. The present study aimed to investigate the stimulating effects of PLT on starch hydrolysis, starch structure and functional properties of GBR. The PLT substantially boosted α-amylase activity during brown rice germination, leading to a 10.9% reduction in total starch content and a 17.3% increase in reducing sugar content, accompanied by elevated free water levels. Structural analysis indicated no changes in starch crystalline types, whereas gelatinization temperature slightly increased. Pasting properties exhibited a significant drop in peak viscosity. Scanning electron microscopy showed surface erosion of starch granules with microstructural changes. Furthermore, correlation analysis established positive links between α-amylase activity, reducing sugar accumulation, starch structure and functional properties in GBR. The present study demonstrates that PLT enhanced the physicochemical properties of GBR starch, significantly improving the stability of GBR products, thereby contributing to expanded applicability of rice starch in the food industry. © 2023 Society of Chemical Industry.


Participation of Na+ channels in the response of carotid body chemoreceptor cells to hypoxia.
The role played by Na+ channels of carotid body (CB) chemoreceptor cells was investigated by studying the effects of tetrodotoxin (TTX) on the release of 3H-labeled catecholamines ([3H]CA) by adult rabbit CBs previously incubated with the precursor [3H]tyrosine. TTX inhibited partially the release of [3H]CA elicited by mild hypoxia (10 or 7% O2) or by depolarizing incubation medium containing 20 or 30 mM KCl, but the response to more intense hypoxia (5 or 2% O2) or to higher KCl concentration (40 or 50 mM) was not significantly affected. The release of [3H]CA elicited by acidic stimuli, either 20% CO2 (pH 6.6) or the protonophore dinitrophenol (100 microM), although comparable in magnitude to that elicited by mild hypoxia, was not modified by TTX. These results provide evidence for the first time that Na+ channels of chemoreceptor cells participate in the transduction of hypoxic stimuli into the neurotransmitter release response of these cells and suggest that Na+ current operates as an amplifying device that enhances the initial cell depolarization mediated by the closure of the O2-sensitive K+ channels. Sympathetic denervation of CBs was followed by a marked reduction in the release of [3H]CA elicited by veratridine or by 20 mM KCl, suggesting that the number of Na+ channels in chemoreceptor cells decreases after denervation.


Characterization of cDNAs encoding small and large subunits of ADP-glucose pyrophosphorylases from watermelon (Citrullus vulgaris S.).
Three cDNA clones encoding ADP-glucose pyrophosphorylases were isolated from a full red fruit cDNA library of watermelon (Citrullus vulgaris S.). Sequence analyses indicated that one clone, wms1, corresponds to the small subunit, and two clones, wml1 and wml2 (a partial gene), are the large subunits of AGPase. The presumed AGPase proteins encoded by wms1, wml1, and wml2 have 526, 526, and 481 amino acids, respectively. The protein sequences have the conserved amino acids important for the substrate or regulator binding site, with some variation. Developmental changes in the amounts of wms1, wml1, and wml2 transcripts in fruits were measured by northern blot analysis. Their expression levels decreased from the small green to medium green stages, then increased in accordance with fruit ripening, which was different from those of tomato and oriental melon.


Cultured human ocular surface epithelium on therapeutic contact lenses.
This study was initiated after observation of some intriguing epithelial growth properties of contact lenses used as a bandage for patients after pterygium surgery. To determine the efficacy of culturing human ocular surface epithelial cells on therapeutic contact lenses in autologous serum with a view of using this system to transfer epithelial cells to patients with persistent corneal or limbal defects. Excess graft tissue resected from patients undergoing pterygium surgery (n = 3) consisting of limbal epithelium was placed on siloxane-hydrogel contact lenses (lotrafilcon A and balafilcon A). Limbal explants were cultured in media with 10% autologous serum. Morphology, proliferative capacity and cytokeratin profile were determined by phase contrast, light and electron microscopy, and immunohistochemical analysis. Lotrafilcon A contact lenses sustained proliferation and migration from limbal tissue. Cells became confluent after 10-14 days and consisted of 2-3 layers with a corneal phenotype (CK3(+)/CK12(+)/CK19(-)) and a propensity to proliferate (p63(+)). Electron microscopy showed microvilli on the apical surface with adhesive projections, indicating that these cells were stable and likely to survive for a long term. Growth was not observed from limbal explants cultured on balafilcon A contact lenses. A method for culturing human ocular surface epithelium on contact lenses that may facilitate expansion and transfer of autologous limbal epithelial cells while avoiding the risks associated with transplanting allogeneic tissue has been developed. This technique may be potentially useful for the treatment of patients with limbal stem cell deficiency.


The complete chloroplast genome sequence of medicinal plant: Cynanchum thesioides (Asclepiadaceae).
Cynanchum thesioides is a medicinal plant. The complete chloroplast genome sequence of is 158,547 bp in length, contains 131 complete genes, including 85 protein-coding genes (85 PCGs), 8 ribosomal RNA genes (8 rRNAs), and 37 tRNA genes (37 tRNAs). The overall AT content of cp DNA is 62.1%, the corresponding values of the LSC, SSC, and IR regions are 63.7, 67.7, and 56.5%. Phylogenetic tree shows that C. thesioides was identified as the most divergent among the sequenced species of Cynanchum used.


Tetrandrine inhibits proinflammatory cytokines, iNOS and COX-2 expression in human monocytic cells.
Tetrandrine (TET), a bis-benzylisoquinoline alkaloid isolated from the dried root of hang-fang-chi (Stephania tetrandra S. Moore), is traditionally used in China for treating inflammation, hypertension and silicosis. In this study, our aim was to examine the anti-inflammatory mechanism of TET through measuring the inducible nitric oxide synthase (iNOS), cyclooxygenase-1, and -2 (COX-1 and COX-2) expression, cytokines (TNF-alpha, IL-4 and IL-8) formation, nitric oxide (NO) release and prostaglandin E2 (PGE2) generation in lipopolysaccharide (LPS)-induced human monocytic (THP-1) cells. Results showed that TET remarkably suppressed the LPS (1 microg/ml) induction of NO release and PGE2 generation. It also significantly attenuated the LPS-induced transcription of proinflammatory cytokines (TNF-alpha, IL-4 and IL-8) in a dose-dependent manner. Furthermore, TET at 100 microM significantly blocked the LPS induction of iNOS and COX-2 expression, but not the COX-1. Taken together, these results suggest that TET exerts anti-inflammatory effects probably through the suppression of COX-2 and iNOS expression.


Esophageal Cancer Patients Have a High Incidence of Severe Periodontitis and Preoperative Dental Care Reduces the Likelihood of Severe Pneumonia after Esophagectomy.
Poor oral health is a risk factor for causing upper aerodigestive tract tumors, including esophageal cancer. Our aim was to determine the periodontitis rate in our cohort of esophageal cancer patients. We also analyzed whether preoperative dental examination and care reduces the likelihood of severe pneumonia after esophagectomy. Between 2003 and 2014, 529 esophageal cancer patients received esophagectomy at Akita University Hospital. We studied 232 patients who had preoperative dental examinations and care (dental care group) retrospectively and assessed the severity of their periodontitis. The dental care group was compared to 297 patients who did not have preoperative dental care (control group) with respect to the incidence of severe pneumonia after esophagectomy. Ninety-one patients (39.2%) in the dental care group were diagnosed with slight periodontitis and 69 (29.7%) were diagnosed with severe periodontitis. Among all the patients, 69 patients (13.0%) were diagnosed with grade 3B postoperative severe pneumonia. The dental care group had a significantly lower incidence of severe pneumonia than the control group. Moreover, multivariable logistic regression analysis revealed that anastomotic leakage, preoperative dental care, gender and %VC were correlated significantly with the occurrence of postoperative severe pneumonia. Preoperative dental examination and care by a dentist are essential to reduce the likelihood of postoperative severe pneumonia in esophageal cancer patients.


Cross-Sectional Study of Clients' Satisfaction With Outpatient and Inpatient Services of Public Health Facilities of a North Indian State.
Satisfaction with health care services is a desired outcome of health care delivery. Nonetheless, there is scant information on client satisfaction with services provided in public health facilities in India. A cross-sectional study of persons attending public health facilities in Punjab, North India, was carried out in 2016. All district hospitals, subdistrict hospitals, 2 community health centres (CHCs), and 6 primary health centres (PHCs) were randomly selected from each of the 22 districts. A 60-item pre-tested and validated questionnaire was used to collect data. Participants (3278 outpatient department [OPD] and 1614 inpatient department [IPD]) visiting health care facilities were interviewed. Majority of OPD participants were satisfied with registration process, care providers, and personal issues like safety and security at the health facilities. Major domains of dissatisfaction were long waiting time and concern shown for patients during lab tests and x-rays. Most IPD participants were satisfied with care received from nurses and doctors, availability of medicines, and hospital environment. Domains of dissatisfaction were cleanliness of rooms and bathrooms and quietness at night. Varying levels of satisfaction were observed for experiences during stay, information about new medicine being given, pain control, and locomotion to bathroom or using bedpan. Around 71% were likely to recommend the health facility to others. Satisfaction with public health facilities is context dependent. Lack of drugs and supplies, poor information about medicines, long waiting time, poor cleanliness, lack of privacy, and peace were the major reasons for dissatisfaction in our study.


Obesity and stones.
The incidence of urolithiasis has shown a prominent increase in the last two to three decades and evidence-based data have clearly indicated the certain role of obesity and overweight in both children and adults. As a certain component of metabolic syndrome, 'obesity' has been found to have a significant impact on the urinary metabolic risk factors which may be important in stone formation. In this present review article, we aimed to evaluate the possible association between obesity and urolithiasis and related risk factors. The epidemiology, pathophysiology, and management of stone disease in obese cases will be discussed in detail. The possible influence of overweight/obesity on the metabolic stone-forming risk factors has been subjected to several studies which in turn well demonstrated the increased risk of stone formation in this population. Although the exact underlying mechanisms are still to be outlined, some certain pathogenetic factors, namely, changes in urinary pH and increased excretion of some urinary stone components have been well demonstrated. Given this increased risk status, these cases require a more comprehensive workup for urolithiasis. Appropriate metabolic evaluation-based medical therapy alongside dietary recommendations will be effective in preventing stone formation. Patients suffering from obesity problem have particular risk factors for urolithiasis when compared with their normal-weight counterparts. All efforts should be taken to increase the awareness of this problem and necessary precautions with well-planned treatment plan are the main tasks for urologists.


Comparison of the efficacy of pterygium resection combined with conjunctival autograft versus pterygium resection combined with amniotic membrane transplantation.
To compare the efficacy of pterygium resection combined with conjunctival autograft versus pterygium resection combined with amniotic membrane transplantation in the treatment of pterygium. A total of 118 cases (133 eyes) were randomly assigned to receive pterygium resection combined with conjunctival autograft (n=81) or pterygium resection combined with amniotic membrane transplantation (n=52). Corneal wound healing and neovascularization and the presence or absence of conjunctival proliferation and hyperemia were analyzed at 12 months post-operatively. In the conjunctival autograft group, 6 eyes (7.4%) had recurrent pterygium, while in the amniotic membrane transplantation group, 10 eyes showed recurrence (19.2%, P<0.05, chi-square). Patients in the conjunctival autograft group recovered significantly faster compared with those in the amniotic membrane transplantation group. Patients receiving pterygium surgery combined with conjunctival autograft had lower recurrence rates and experience faster recovery compared with those undergoing pterygium resection combined with amniotic membrane transplantation.


[Systematic study of sequential salivary gland scintigraphy during rheumatoid arthritis and collagenosis. Apropos of 150 examinations].
Sequential salivary scintigraphy has been practised systematically in 130 patients hospitalized in a rheumatology unit. These patients were suffering from typical, classical rheumatoid arthritis, rheumatoid arthritis with high positivity for anti-nuclear antibodies, clearly defined polyarthritis, systemic scleroderma, other types of collagenosis, forms of inflammatory polyarticular rheumatism other than rheumatoid arthritis and collagenosis, and from different degenerative diseases. The scintigraphic anomalies were divided in three stages according to a personal classification. Nine patients presented a patend Gougerot-Sjögren syndrome. All of them had abnormal or very abnormal scintigraphy. However, the patients with classical rheumatoid arthritis without signs of the Gougerot-Sjögren syndrome, also showed a high frequency of isotopic anomalies that were equally severe. These were clearly connected only with the particular diagnosis (with classical rheumatoid arthritis, but not with clearly defined polyarthritis or collagenosis). No other direct relationship could be established between these diseases and the clinical, radiological, laboratory, or therapeutic aspects of the case. On the other hand, they were often associated with a reduction in lacrymal and salivary secretion. These isotopic studies, in combination with other findings shed a new light on the Gougerot-Sjögren syndrome, taking into account the diffusion of the exocrine lesions and of the contributions of the most modern methods of investigation.


Sports Medicine Staffing Across National Collegiate Athletic Association Division I, II, and III Schools: Evidence for the Medical Model.
The ratio of clinicians to patients has been associated with health outcomes in many medical contexts but has not been explored in collegiate sports medicine. The relationship between administrative and financial oversight models and staffing is also unknown. To (1) evaluate staffing patterns in National Collegiate Athletic Association sports medicine programs and (2) investigate whether staffing was associated with the division of competition, Power 5 conference status, administrative reporting structure (medical or athletic department), or financial structure (medical or athletic department). Cross-sectional study. Collegiate sports medicine programs. Representatives of 325 universities. A telephone survey was conducted during June and July 2015. Participants were asked questions regarding the presence and full-time equivalence of the health care providers on their sports medicine staff. The number of athletes per athletic trainer was determined. Responding sports medicine programs had 0.5 to 20 full-time equivalent staff athletic trainers (median = 4). Staff athletic trainers at participating schools cared for 21 to 525 athletes per clinician (median = 100). Both administrative and financial oversight from a medical department versus the athletics department was associated with improved staffing across multiple metrics. Staffing levels were associated with the division of competition; athletic trainers at Division I schools cared for fewer athletes than athletic trainers at Division II or III schools, on average. The support of graduate assistant and certified intern athletic trainers varied across the sample as did the contributions of nonphysician, nonathletic trainer health care providers. In many health care settings, clinician : patient ratios are associated with patient health outcomes. We found systematic variations in clinician : patient ratios across National Collegiate Athletic Association divisions of competition and across medical versus athletics organizational models, raising the possibility that athletes' health outcomes vary across these contexts. Future researchers should evaluate the relationships between clinician : patient ratios and athletes' access to care, care provision, health care costs, health outcomes, and clinician job satisfaction.


Should children and adolescents undergo genetic testing?
Genetic testing comes in many shapes and sizes. The decision to undergo genetic testing must involve consideration of the medical, psychosocial, and reproductive benefits and risks of testing. The evaluation of risks and benefits varies significantly both between and within families. Pediatricians should keep up with the rapid advances in genetic medicine and the myriad of tests that are being developed and marketed. They also need to be familiar with the psychosocial risks and benefits that these new tests generate for individuals, families and communities. In some situations, genetic testing is merely another diagnostic tool; in other situations, genetic testing offers information about the risks for future diseases. Pediatricians need to be knowledgeable about tests that are indicated clinically and their potential psychosocial implications to best serve children, adolescents, and their families.


[Eccrine-nevus (author's transl)].
The eccrine nevus is an exceptional entity, formed by well-differentiated adnexa which can be classified as hamartoma or organoid nevus. It is characterized by a high degree of structural maturation. The authors report a case of eccrine nevus observed in a 32-year-old woman and compare clinical and histological features of the lesion with literature data.


EVALUATION OF THE BONE MINERAL DENSITY OF ASIAN ELEPHANTS (ELEPHAS MAXIMUS) VIA DUAL-ENERGY X-RAY IMAGING OF TAILS.
Musculoskeletal problems are one of the top five causes of disease in elephants. However, recent blood chemistry analysis is the only routine protocol for bone mineral status evaluation, with no assessment method currently available for the direct measurement of elephant bone mineral density (BMD). This work applied the the dual-energy X-ray technique (DXA) technique for bone density assessment. The elephant's tail was chosen for the analysis to avoid the radiation harm. Twelve live Asian elephants (Elephas maximus) comprising eight males and four females with ages in the range of 4-77 yr were investigated. The BMD was calculated based on radiographic images acquired using the DXA technique carried out at 40 kVp 2 mAs and 50 kVp 2 mAs. Blood serum analysis of total calcium (Ca), phosphorus (Phos) and alkaline phosphatase (ALP) content was conducted in parallel with the physical examination to correlate age and BMD. Analyses produced an overall mean BMD value in the range of 0.54-1.39 g/cm2, with that of the males higher than that of the females. The BMD was found to be negatively correlated with age, Ca, and Phos, but not with ALP. In summary, the BMD analysis of an elephant's tail might be used with blood serum Ca and Phos to predict the overall bone mineral status of the animal.


Icaritin acts synergistically with epirubicin to suppress bladder cancer growth through inhibition of autophagy.
Bladder cancer is one of the most commonly diagnosed urological malignancies. Acquired resistance to chemotherapy is a great barrier for achieving successful treatment of bladder cancer. In the present study, we investigated the effect and mechanisms of icaritin, a flavonol glycoside derived from genus Epimedium, against human bladder cancer cells. It was found that despite the low cytotoxicity in normal human HEK293 cells, icaritin significantly inhibited the proliferation and colony formation of BT5637 and T24 bladder cancer cells time- and dose-dependently compared to the DMSO vehicle control. Moreover, cell viability monitored through mitochondrial membrane potential was inhibited markedly after icaritin treatment. Further investigation indicated that icaritin may inhibit epirubicin (EPI)-induced autophagy, and acted synergistically with EPI to suppress the proliferation of BT5637 and T24 cells. These findings suggest that icaritin may prove to be a novel potent therapeutic agent for the treatment of bladder cancer.


[Nature medicine as intoxicant].
Documentation is often scarce about adverse effects of herbal products used in alternative medicine. Five patients were admitted to hospital with altered consciousness after taking the herbal product Relaxir, a remedy for insomnia and restlessness, produced mainly from the fruit from the passion flower (Passiflora incarnata). Relaxir is thought to have an intoxicating and sedative effect and may also potentiate the effect of other drugs. It is questionable that herbal products liable to cause intoxication are sold without restriction.


Recovery of bacteria from growth media by starch-dependent floc formation.
Addition of starch to suspensions of Escherichia coli K-12 resulted in the formation of bacterial flocs. The flocculation was dependent on the high expression of a receptor for starch (maltoporin) on the surface of the bacterium. Factors influencing floc formation were investigated and optimal conditions for flocculation based on cell density, starch concentration, time, and pH established. As quantitated by a sedimentation assay, over 80% of bacteria in a culture could be removed by settling without centrifugation in 3 h under optimal conditions. Floc formation was evident with bacteria containing wild-type maltoporin but was faster and occurred to a greater extent with strains expressing a high-affinity allele (lamB1400) of the starch receptor. Bacteria could be harvested by floc formation directly in growth medium under defined conditions of maltoporin expression and medium composition. These results demonstrate the effectiveness of starch-dependent aggregation in the harvesting of cells, using an inexpensive, biologically acceptable agent to induce flocculation.


Effects of cyclosporin A and insulin on peripheral lymphocytes in BB/W rats.
The effects of cyclosporin A (Cs-A) and insulin on peripheral lymphocytes in BB/W rats were studied. The cumulative incidence of overt diabetes in untreated BB/W rats was 72% up to 120 days of observation, whereas the incidence was 13% in Cs-A-treated rats. Lymphocytopenia, consisting of decreased OX19+ (pan T), W3/25+ (helper/inducer T) and OX8+ (cytotoxic/suppressor T) cells, was present in BB/W rats. Cs-A significantly decreased both the percentage and the absolute number of OX8+, OX6+ (Ia-positive) and OX12+ (B) cells, and augmented the ratio of W3/25+ to OX8+ cells in BB/W rats. On the other hand, insulin injection significantly decreased the percentage of OX6+ cells and the ratio of W3/25+ to OX8+ cells in BB/W rats. Thus, rearrangement of the ratio of helper/inducer T to cytotoxic/suppressor T cells and reduction in the number of Ia antigen-bearing cells could be important for the inhibitory effects of diabetes in BB/W rats upon treatment with Cs-A or insulin.


Cobalamin and folate status in women during early pregnancy in Bhaktapur, Nepal.
The demand for cobalamin (vitamin B12) and folate is increased during pregnancy, and deficiency during pregnancy may lead to complications and adverse outcomes. Yet, the status of these micronutrients is unknown in many populations. We assessed the concentration of cobalamin, folate and their functional biomarkers, total homocysteine (tHcy) and methylmalonic acid (MMA), in 561 pregnant women enrolled in a community-based randomised controlled trial in Bhaktapur, Nepal. Plasma concentrations of cobalamin, folate, tHcy and MMA were measured and a combined indicator of vitamin B12 status (3cB12) was calculated. We report mean or median concentrations and the prevalence of deficiency according to commonly used cut-offs, and assessed their association with indicators of socio-economic status, and maternal and dietary characteristics by linear regression. Among the women at gestational week less than 15, deficiencies of cobalamin and folate were seen in 24 and 1 %, respectively. Being a vegetarian was associated with lower plasma cobalamin, and a higher socio-economic status was associated with a better micronutrient status. We conclude that cobalamin deficiency defined by commonly used cut-offs was common in Nepalese women in early pregnancy. In contrast, folate deficiency was rare. As there is no consensus on cut-off points for vitamin B12 deficiency during pregnancy, future studies are needed to assess the potential functional consequences of these low values.


THIOUREA DERIVATIVES OF 4-AZATRICYCLO[184.108.40.206(2.6)]UNDEC-8-ENE-3,5 DIONE - SYNTHESIS AND BIOLOGICAL ACTIVITY.
A series of halogeno derivatives of thiourea bearing a polycyclic imide core has been efficiently synthesized and evaluated for antimicrobial activity. The structures of the compounds were established by 1H and 13C NMR and MS methods. The molecular structure of 4Clc was determined by an X-ray crystallography. Compounds containing 3-chloro-4-fluorophenyl substituent (3Cl4Fb, 3Cl4Fd) were found to be the most promising against Gram-positive bacteria (MIC values ranged from 8 to 32 pg/mL for standard and 32 - 64 µg/mL for hospital strains). The in vitro cytotoxicity against MT-4 cells of all compounds was evaluated.


Stroke, statins, and cholesterol. A meta-analysis of randomized, placebo-controlled, double-blind trials with HMG-CoA reductase inhibitors.
To estimate the effect of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors ("statins") on stroke ris, we combined the data of the randomized, placebo-controlled, double-blind trials with HMG-CoA reductase inhibitors published so far. The studies were identified using the Medline CD+ and Current Contents databases from January 1980 through May 1996, inclusive. All studies were evaluated on the use of a placebo control, monotherapy, and double blindness. When the type of stroke or the occurrence of clinical events or adverse effects were incompletely or not reported, the investigators were contacted personally. For each trial, the number of strokes in the treatment arm was compared with the number of strokes expected on all observations under the assumption that drug treatment had no effect. A total of 462 strokes among 20438 participants in 13 trials could be analyzed. A total of 181 strokes were observed in patients randomized to treatment with an HMG-CoA reductase inhibitor and 261 strokes in patients randomized to placebo. A lower than expected number of strokes was observed in the treatment groups of all but one trial (P = .001). Treatment with an HMG-CoA reductase inhibitor led to an overall risk reduction of 31% (odds ratio, 0.69; 95% confidence interval, 0.57 to 0.83). The combined data suggest that treatment with HMG-CoA reductase inhibitors prevents stroke in middle-aged persons. Because stroke is especially common in older age, these data reinforce the need for clinical trials to evaluate the effect of HMG-CoA reductase inhibitors in preventing stroke in the elderly.


Joint analysis of the influence of CYP11B1 and DGAT1 genetic variation on milk production, somatic cell score, conformation, reproduction, and productive lifespan in German Holstein cattle.
Recent publications indicate genetic variation in milk production traits on proximal BTA14, which cannot be explained solely with genetic variation in the DGAT1 gene. To elucidate these QTL effects, animals from a German Holstein granddaughter design (18 families, 1,291 sons) were genotyped for CYP11B1 (V30A) and DGAT1 (K232A) polymorphisms. Frequencies of alleles of maternal descent were estimated for CYP11B1(V) (0.776) and DGAT1(K) (0.549). Allele substitution effects (alpha/2) were first calculated for both alleles in separate models and then in a joint model. From the joint analysis, CYP11B1(V) effects on fat content (+0.04%) and protein content (+0.01%) were positive. Effects on milk yield (-82 kg), fat yield (-0.5 kg), and protein yield (-1.9 kg) were negative. Compared with the individual analysis, DGAT1(K) effects on fat content (+0.28%), protein content (+0.06%), and milk yield (-258 kg) were reduced; fat yield (+10.8 kg) was enhanced; and protein yield (-3.8 kg) was reduced. In the joint analysis, allele substitution effects of CYP11B1(V) and DGAT1(K) together explained more of the variation in milk production traits than DGAT1(K) alone. Further significant effects were found for CYP11B1(V) and DGAT1(K) among 6 reproduction traits and 14 conformational traits. These observations indicate a possible negative influence of DGAT1(K) on maternal nonreturn rate, and thus, on length of productive life.


Are fashion models a group at risk for eating disorders and substance abuse?
Few studies to date have investigated whether in fact the prevalence of eating disorders (ED) and/or use of illicit drugs is higher among models than among other groups of females. A group of 63 professional fashion models of various nationalities were studied by means of self-reported questionnaires. They were compared with a control group of 126 female subjects recruited from the general population. Fashion models weigh significantly less than controls, but only a small percentage of them uses unhealthy methods to control their weight. The current frequency of full-syndrome ED did not differ between the groups, but partial-syndrome ED were significantly more common among fashion models than among controls. Current substance use or alcohol abuse was reported by 35% of fashion models and 12% of controls. Our findings suggest that fashion models are more at risk for partial ED and use of illicit drugs than females in the general population.


[Applying Team Resource Management to Accelerate Rewarming Among Patients Undergoing General Anesthesia].
Hypothermia is the cause of multiple problems such as delayed awaking from anesthesia, feelings of discomfort, increased oxygen consumption, and increased risks of surgical wound infection and complications. A review of the record of post-operative patients receiving general anesthesia (GA) revealed that only 74% of the patients in our post-anesthesia room (PAR) had restored their body temperature to 36℃ after 60 minutes. Through situation analysis, several causes were identified, including insufficient warming facilities, lack of standard procedures and an audit system, lack of knowledge regarding hyperthermia among nurses, and the incompleteness of perioperative warming interventions performed by the healthcare team. The aim of the present project was to apply team resource management (TRM) to raise the rate of body temperature restoration to 36°C after 60 minutes in our post-anesthesia room (PAR) from 74% to 100%. Several strategies were implemented to accelerate the post-operative rewarming for patients receiving GA, including: establishment of standard operating procedures for warming, conducting routine audits, purchasing warming facilities, conducting in-service education, applying TRM, and cooperating with nurses in operating rooms on executing the warming plan. After implementing these strategies, our PAR achieved a 100% success rate in raising the body temperature of postoperative patients to 36°C after 60 minutes. The result demonstrates that hypothermia may be effectively avoided and that the quality of post-operative care may be effectively improved through transdisciplinary teamwork.


The influence of age structure and fecundity on effective population size.
Simple formulae are developed which define the effective size (Ne) of populations with overlapping generations, and their use is illustrated using data from a squirrel population. Two mating systems are considered, the random union of gametes and monogamy, in combination with age-independent fecundity. In the simplest case of age-independent (type 2) survivorship in a population of N adults, Ne = N/(2-T-1) where T is the generation time. As T increases, Ne declines asymptomatically to N/2. A generalization of this result (Ne = N/[1 + k-1-T-1], where k influences survivorship) shows that given type 1 survivorship (k greater than 1) this decline in Ne is less severe. A biased sex ratio results in Ne differing between the two mating systems; however, in both systems, a sex ratio bias resulting from survival differences has much less influence on Ne than a sex ratio bias resulting from recruitment differences. Low fecundity can increase Ne, but realistic levels of variation among breeding individuals (Poisson or greater) negate the effect. The effect on Ne of variation resulting from the presence of non-breeders is also considered.


Social cognition in context: validating a cartoon-based attributional measure for urban girls.
Standard approaches to the development of psychological measures emphasize the role of the research team in identifying constructs, generating and retaining items, and establishing psychometric soundness. Although there are a number of strengths associated with these methods, the resulting measures may not be culturally sensitive to minority cultural groups. In order to address this need, the authors partnered with African American inner-city 3rd- and 4th-grade girls (predominantly 9- and 10-year-olds) to design and validate a cartoon-based hostile attributional bias measure that is developmentally and culturally sensitive. This paper illustrates how a partnership-based research model can be used to design measurement tools sensitive to the ways in which developmental processes are influenced by an urban, low-income, ecological context.


Differential expression of apolipoprotein d in human astroglial and oligodendroglial cells.
Apolipoprotein D (Apo D) is a secreted lipocalin in the nervous system that may be related to processes of reinnervation and regeneration. Under normal conditions, Apo D is present in the central nervous system in oligodendrocytes, astrocytes, and some scattered neurons. To elucidate the regional and cellular distribution of Apo D in normal human brain, we performed double immunohistochemistry for glial fibrillary acidic protein (GFAP) and Apo D in samples of postmortem human cerebral and cerebellar cortices. Most of the GFAP-positive cells in the gray matter had features of protoplasmic astrocytes and were mainly Apo D-positive. Apo D staining was mostly confined to the cell soma and proximal processes, whereas GFAP extended to a rich and extensive array of processes. The fibrous astrocytes in the white matter were immunoreactive for GFAP but not for Apo D. In the white matter, Apo D was mainly detected in oligodendrocytes and extracellularly in the neuropil. The results of the present study support a specific behavior for each astrocyte type. These findings suggest that Apo D expression may be cell-specific, depending on the particular tissue physiology at the time of examination.


Assessing the Safety of Expanded Polytetrafluoroethylene Synthetic Grafts in Living Donor Liver Transplantation: Graft Migration Into Hollow Viscous Organs - Diagnosis and Treatment Options.
BACKGROUND Our recent studies have highlighted the importance and safety of backtable venoplasty for middle hepatic vein (MHV) and inferior right hepatic veins (IRHV) reconstruction using expanded polytetrafluoroethylene (ePTFE) vascular grafts. In this study, we aim to analyze the complications associated with ePTFE graft use and discuss the management of the rare, but, potentially life threatening complications directly related to ePTFE conduits. MATERIAL AND METHODS From January 2012 to October 2015 a total of 397 patients underwent living donor liver transplantation (LDLT). The ePTFE vascular grafts were used during the backtable venoplasty for outflow reconstruction in 262 of the liver allografts. Recipients who developed ePTFE-related complications were analyzed. RESULTS ePTFE-related complications developed in 1.52% (4/262) of the patients. One patient (0.38%) developed complete thrombosis with sepsis at 24 months post-transplantation and died due to multiorgan failure. Three patients (1.1%) developed graft migration into the second portion of the duodenum, without overt peritonitis. Surgical exploration and ePTFE graft removal was done in all the patients. One patient died due to overwhelming sepsis. CONCLUSIONS ePTFE graft migration into the duodenum causing perforation is a new set of complications that has been recently described in LDLT and can be treated effectively by surgical removal of the infected vascular graft and duodenal perforation closure. Despite of such complications, in our experience, ePTFE use in LDLT continues to have wide safety margin, with a complication rate of only 1.52%.


Beta-endorphin, ACTH, and cortisol response to hemorrhage in conscious pigs.
Some of the interrelations of neuroendocrine changes associated with hypovolemia were investigated in a model simulating an arterial hemorrhage. beta-Endorphin, adrenocorticotropin hormone (ACTH), and cortisol levels were measured by radioimmunoassay before, during, and after controlled bleeding of conscious splenectomized pigs. All animals showed significant (P less than 0.05) increases in the three neuroendocrine substances during hemorrhage. beta-Endorphin values initially were 55 +/- 7 pg/ml (+/- SE) and rose to a peak of 386 +/- 44 pg/ml at the nadir of blood pressure (mean arterial pressure = 47.5 mmHg). ACTH showed a similar pattern, increasing from 49 +/- 10 to a peak of 518 +/- 56 pg/ml. Cortisol values reached their peak of 18.2 +/- 2.5 micrograms % during the recovery phase. beta-Endorphin values displayed a close inverse correlation to blood pressure during hemorrhage, but returned to basal levels more rapidly than blood pressure during the recovery period. Plasma ACTH levels rose significantly more slowly than beta-endorphin as the hemorrhage progressed. An equimolar ratio of ACTH and beta-endorphin returned only as levels declined following the hemorrhagic insult. In awake pigs therefore an arterial hemorrhage is accompanied by endorphin release proportional to the decrement in blood pressure, a somewhat retarded buildup of ACTH, and a still later cortisol peak during recovery.


Episomal HIV-1 DNA and its relationship to other markers of HIV-1 persistence.
Reverse transcription of HIV-1 results in the generation of a linear cDNA that serves as the precursor to the integrated provirus. Other classes of extrachromosomal viral cDNA molecules can be found in acutely infected cells including the 1-LTR and 2-LTR circles of viral DNA, also referred as episomal HIV-1 DNA. Circulating CD4+ T-cells of treatment-naïve individuals contain significant levels of unintegrated forms of HIV-1 DNA. However, the importance of episomal HIV-1 DNA in the study of viral persistence during antiviral therapy (ART) is debatable. 2-LTR circles are preferentially observed in the effector memory CD4+ T cell subset of long-term treated subjects. Treatment intensification of standard regimens has been used to determine if more potent ART can impact viral reservoir activity. Adding a potent antiretroviral drug to a stable triple-drug regimen has no measurable impact on plasma HIV-1 RNA levels, suggesting that ongoing cycles of HIV-1 replication are not a major mechanism driving persistent plasma viremia during triple-drug ART. However, in randomized clinical trials of HIV-1-infected adults on apparently effective ART, the addition of an integrase inhibitor (raltegravir) to stable regimens resulted in a transient increase in 2-LTR circles in some patients, suggesting a pre-intensification steady-state in which the processes of virion generation and de novo infection were occurring. Mathematical modeling of 2-LTR production during integrase inhibitor intensification suggests the coexistence, at different levels, of ongoing de novo infection and de novo replication mechanisms, specifically in inflamed lymphoid drug sanctuaries. Most reports looking into potential changes in 2-LTR circles in interventional clinical studies have simultaneously assessed other potential surrogate markers of viral persistence. Transient increases in 2-LTR circles have been correlated to decreases in CD8+ T-cell activation, transient CD45RA-CD4+ T-cell redistribution, and decreases in the hypercoagulation biomarker D-dimer in ART-intensified individuals. It is difficult, however, to establish a systematic association because the level of correlation with different types of markers differs significantly among studies. In conclusion, despite suppressive ART, a steady-state of de novo infection may persist in some infected individuals and that this may drive immune activation and inflammation changes reflecting residual viral reservoir activity during otherwise apparently suppressive ART.


Stimulation of 5-HT2A receptors on astrocytes in primary culture opens voltage-independent Ca2+ channels.
Mechanisms underlying the 5-HT2A receptor induction of intracellular Ca2+ mobilization and Ca2+ influx in type I astroglial cells in primary culture from newborn rat cerebral cortex were evaluated. The 5-HT-evoked Ca(2+)-transients, inhibited by the 5-HT2A antagonists ketanserin or 4-(4-fluorobenzoyl)-1-(4-phenylbutyl) piperidine oxalate, consisted of an initial peak caused by inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ release from internal stores, and a second sustained part which was due to Ca2+ transport over the plasma membrane. The responses were pertussis toxin-insensitive, suppressed by the phospholipase C inhibitor neomycin and were inhibited by the Ca(2+)-ATPase inhibitor thapsigargin. Furthermore, the responses were inhibited by the IP3 receptor antagonist heparin. When the second sustained part of the 5-HT-evoked response was studied, it was concluded that Ca2+ influx was not a result of opening of voltage operated calcium channels of either L, N or T-type. Instead it appeared that Ca2+ entered the cells through specialized voltage independent Ca2+ channels which were dependent of the IP3 production and subsequent Ca2+ release from internal stores. From this, we conclude that 5-HT opens Ca2+ channels in astrocytes which closely resemble depletion-operated Ca2+ channels (DOCCs).