Barriers to Medications for Opioid Use Disorder Among Veterans Involved in the Legal System: a Qualitative Study.
Veterans involved in the legal system are at high risk for overdose but have lower receipt of medications for opioid use disorder than other veterans. The study aimed to understand barriers to medication access from the perspective of legally involved veterans with opioid use disorder and people who work with these veterans in the Veterans Health Administration (VHA) and the legal system. This national qualitative study interviewed veterans and stakeholders from 14 geographically diverse VHA facilities to explore perceptions of barriers to medications for opioid use disorder. Participants included veterans with a history of opioid use disorder and legal involvement (n = 18), VHA Veterans Justice Programs Specialists (n = 15), VHA and community substance use disorder treatment providers (n = 5), and criminal justice staff (n = 12). We conducted interviews based on the Consolidated Framework for Implementation Research. Interview transcripts were analyzed using a team-based approach. Four key barriers, noted by group, were identified: (1) a preference for counseling along with or instead of medications (veterans, Specialists, treatment providers, criminal justice staff); (2) concerns about veterans using medications without a prescription, selling them, or providing them to others (veterans, Specialists, treatment providers, criminal justice staff); (3) concerns about perceived stigma towards medication use (veterans, Specialists, treatment providers, criminal justice staff); and (4) concerns about medication discontinuation after recurrent opioid use (veterans, criminal justice staff). A fifth theme, education, was noted by all stakeholders except providers as important to facilitating use of medications for opioid use disorder. All five themes mapped to the framework construct of knowledge and beliefs about the intervention. Based on identified barriers, interventions focused on enhancing medication knowledge, reducing stigma towards use of medications, and increasing knowledge that opioid use may recur during treatment may help increase access to medication for veterans with legal involvement.


Photoprotection in a zeaxanthin- and lutein-deficient double mutant of Arabidopsis.
When light absorption by a plant exceeds its capacity for light utilization, photosynthetic light harvesting is rapidly downregulated by photoprotective thermal dissipation, which is measured as nonphotochemical quenching of chlorophyll fluorescence (NPQ). To address the involvement of specific xanthophyll pigments in NPQ, we have analyzed mutants affecting xanthophyll metabolism in Arabidopsis thaliana. An npq1 lut2 double mutant was constructed, which lacks both zeaxanthin and lutein due to defects in the violaxanthin de-epoxidase and lycopene in-cyclase genes. The npq1 lut2 strain had normal Photosystem II efficiency and nearly wild-type concentrations of functional Photosystem II reaction centers, but the rapidly reversible component of NPQ was completely inhibited. Despite the defects in xanthophyll composition and NPQ, the npq1 lut2 mutant exhibited a remarkable ability to tolerate high light.


Immunocytochemical staining for human chorionic gonadotropin subunits does not predict malignancy in insulinomas.
Insulinomas, the most common pancreatic endocrine tumors, produce a clinical syndrome of hyperinsulinism and hypoglycemia. Although the majority of insulinomas are benign, a significant proportion (4-16%) behave aggressively. Because malignant potential cannot be assessed adequately by histopathologic criteria, reliable serum and immunocytochemical markers for malignancy have been sought. Recent reports suggest that subunits of human chorionic gonadotropin (hCG) are of prognostic value in pancreatic endocrine tumors. Elevated serum levels of either the alpha-subunit or beta-subunit of hCG have been reported to be associated with malignancy in pancreatic endocrine tumors. Both hCG and its alpha-subunit have been demonstrated in malignant pancreatic endocrine tumors by immunohistochemistry. In this study, 17 insulinomas have been analyzed by immunohistochemistry using monospecific antibodies to both the alpha-subunit and beta-subunit of hCG. Clinical follow-up was obtained in all cases, and four of the tumors proved to be malignant. Alpha-subunit immunoreactivity was found in only two tumors, both of which were benign. Immunoreactivity for the beta-subunit was not found in any tumor. The authors' results indicate that for this subset of pancreatic endocrine tumors, staining for hCG subunits is of no value in predicting malignant behavior.


Pseudopulse near-field subsurface tomography.
Decisive success has been achieved in developing the subsurface near-field scanning tomography that overcomes the Rayleigh diffraction limit of a resolution. It is related to the transformation of the multifrequency inverse scattering problem to that for a complex-valued synthesized pulse (pseudopulse). It leads to the integral equation that has maxima in the depth dependence of its kernel and, hence, to the much better depth resolution of tomography. Moreover, the noise related to surface scattering is mainly suppressed in such an approach. This idea is realized here in the microwave subsurface tomography of 3D inhomogeneous dielectric structures. For homogeneous dielectric targets, this approach is applied to obtain holography images of their shape.


Regulatory functions of CD8+CD28- T cells in an autoimmune disease model.
CD8+ T cell depletion renders CD28-deficient mice susceptible to experimental autoimmune encephalomyelitis (EAE). In addition, CD8-/-CD28-/- double-knockout mice are susceptible to EAE. These findings suggest a role for CD8+ T cells in the resistance of CD28-deficient mice to disease. Adoptive transfer of CD8+CD28- T cells into CD8-/- mice results in significant suppression of disease, while CD8+CD28+ T cells demonstrate no similar effect on the clinical course of EAE in the same recipients. In vitro, CD8+CD28- but not CD8+CD28+ T cells suppress IFN-gamma production of myelin oligodendrocyte glycoprotein-specific CD4+ T cells. This suppression requires cell-to-cell contact and is dependent on the presence of APCs. APCs cocultured with CD8+CD28- T cells become less efficient in inducing a T cell-dependent immune response. Such interaction prevents upregulation of costimulatory molecules by APCs, hence decreasing the delivery of these signals to CD4+ T cells. These are the first data establishing that regulatory CD8+CD28- T cells occur in normal mice and play a critical role in disease resistance in CD28-/- animals.


Unraveling the complex nature of prostate cancer stem cells.
The identification of distinct prostate cancer stem cell biomarkers is necessary as researchers attempt to isolate, characterize, and therapeutically target these tumor initiating cells. However, in reading the current literature it is frequently difficult to discern which biomarkers and cellular characteristics identify prostate cancer stem cells as opposed to the general population of prostate cancer cells or normal prostate stem cells. Within this review, we address this issue by dissecting out the cell surface markers, adhesion and cytoskeletal proteins, signaling pathways, epigenetic modifications, and the effects of androgens that are specific to and help to define the prostate cancer stem cell.


Intensivist physician staffing and the process of care in academic medical centres.
Although intensivist physician staffing is associated with improved outcomes in critical care, little is known about the mechanism leading to this observation. To determine the relationship between intensivist staffing and select process-based quality indicators in the intensive care unit. Retrospective cohort study in 29 academic hospitals participating in the University HealthSystem Consortium Mechanically Ventilated Patient Bundle Benchmarking Project. 861 adult patients receiving prolonged mechanical ventilation in an intensive care unit. Patient-level information on physician staffing and process-of-care quality indicators were collected on day 4 of mechanical ventilation. By day 4, 668 patients received care under a high intensity staffing model (primary intensivist care or mandatory consult) and 193 patients received care under a low intensity staffing model (optional consultation or no intensivist). Among eligible patients, those receiving care under a high intensity staffing model were more likely to receive prophylaxis for deep vein thrombosis (risk ratio 1.08, 95% CI 1.00 to 1.17), stress ulcer prophylaxis (risk ratio 1.10, 95% CI 1.03 to 1.18), a spontaneous breathing trial (risk ratio 1.37, 95% CI 0.97 to 1.94), interruption of sedation (risk ratio 1.64, 95% CI 1.13 to 2.38) and intensive insulin treatment (risk ratio 1.40, 95% CI 1.18 to 1.79) on day 4 of mechanical ventilation. Models accounting for clustering by hospital produced similar estimates of the staffing effect, except for prophylaxis against thrombosis and stress ulcers. High intensity physician staffing is associated with increased use of evidence-based quality indicators in patients receiving mechanical ventilation.


Home Manufacture of Drugs: An Online Investigation and a Toxicological Reality Check of Online Discussions on Drug Chemistry.
Emerging trends in market dynamics and the use of new psychoactive substances are both a public health concern and a complex regulatory issue. One novel area of investigation is the availability of homemade opioids, amphetamines and dissociatives, and the potential fueling of interest in clandestine home manufacture of drugs via the Internet. We illustrate here how online communal folk pharmacology of homemade drugs on drug website forums may actually inform home manufacture practices or contribute to the reduction of harms associated with this practice. Discrepancies between online information around purification and making homemade drugs safer, and the synthesis of the same substances in a proper laboratory environment, exist. Moderation and shutdown of synthesis queries and discussions online are grounded in drug websites adhering to harm-reduction principles by facilitating discussions around purification of homemade drugs only. Drug discussion forums should consider reevaluating their policies on chemistry discussions in aiming to reach people who cannot or will not refrain from cooking their own drugs with credible information that may contribute to reductions in the harms associated with this practice.


HLA-DPB1 mismatch alleles represent powerful leukemia rejection antigens in CD4 T-cell immunotherapy after allogeneic stem-cell transplantation.
Refractory or relapsed acute myeloid leukemia (AML) represents a frequent complication after allogeneic hematopoietic stem-cell transplantation (HSCT). We show herein that primary in vitro stimulation of CD45RA-selected CD4 T cells of stem-cell donors with 10/10 HLA-matched AML blasts results in expansion of cytolytic T-lymphocytes (CTL) that almost all recognize HLA-DPB1 mismatch alleles, which clinically occur in up to 80% of donor-patient pairs. Primary AML blasts were found to strongly express HLA-DPB1, whereas fibroblasts and keratinocytes used as surrogate target cells for graft-versus-host disease did express HLA-DPB1 only upon IFN-γ pre-treatment. Since patients' AML blasts are rarely available in clinical routine, we developed a protocol based on stimulation of donor-derived CD45RA-selected CD4 T cells with autologous dendritic cells electroporated with RNA encoding patients' HLA-DPB1 mismatch alleles. Short-term stimulated T cell-lines specifically lysed HLA-DPB1 mismatch-expressing AML blasts, but not fibroblasts and keratinocytes without IFN-γ pre-treatment. Notably, these CD4 CTL efficiently eliminated AML blasts upon adoptive transfer into leukemia-engrafted NSG mice. In conclusion, we show strong immunogenicity of HLA-DPB1 mismatch alleles in CD45RA-selected CD4 T cells of stem-cell donors and introduce a novel strategy to reliably generate HLA-DPB1-specific CD4 CTL that might be powerful cellular therapeutics in relapsed or refractory AML after HSCT.


Self-assembly of sensory neurons into ganglia-like microtissues.
Unraveling intra- and inter-cellular signaling networks managing cell-fate control, coordinating complex differentiation regulatory circuits and shaping tissues and organs in living systems remain major challenges in the post-genomic era. Resting on the laurels of past-century monolayer culture technologies, the cell culture community has only recently begun to appreciate the potential of three-dimensional mammalian cell culture systems to reveal the full scope of mechanisms orchestrating the tissue-like cell quorum in space and time. Capitalizing on gravity-enforced self-assembly of monodispersed primary embryonic mouse cells in hanging drops, we designed and characterized a three-dimensional cell culture model for ganglion-like structures. Within 24h, a mixture of mouse embryonic fibroblasts (MEF) and cells, derived from the dorsal root ganglion (DRG) (sensory neurons and Schwann cells) grown in hanging drops, assembled to coherent spherical microtissues characterized by a MEF feeder core and a peripheral layer of DRG-derived cells. In a time-dependent manner, sensory neurons formed a polar ganglion-like cap structure, which coordinated guided axonal outgrowth and innervation of the distal pole of the MEF feeder spheroid. Schwann cells, present in embryonic DRG isolates, tended to align along axonal structures and myelinate them in an in vivo-like manner. Whenever cultivation exceeded 10 days, DRG:MEF-based microtissues disintegrated due to an as yet unknown mechanism. Using a transgenic MEF feeder spheroid, engineered for gaseous acetaldehyde-inducible interferon-beta (ifn-beta) production by cotransduction of retro-/ lenti-viral particles, a short 6-h ifn-beta induction was sufficient to rescue the integrity of DRG:MEF spheroids and enable long-term cultivation of these microtissues. In hanging drops, such microtissues fused to higher-order macrotissue-like structures, which may pave the way for sophisticated bottom-up tissue engineering strategies. DRG:MEF-based artificial micro- and macrotissue design demonstrated accurate key morphological aspects of ganglions and exemplified the potential of self-assembled scaffold-free multicellular micro-/macrotissues to provide new insight into organogenesis.


Effects of Mental Health Support on the Grief of Bereaved People Caused by Sewol Ferry Accident.
Few studies have assessed the overall effects of multi-centered, complicated mental health support on the grief process. This study investigated the broader influence of mental health support provided practically to the bereaved family on the severity of complicated grief. Ninety-three bereaved family members of the Sewol ferry accident were recruited. Severity of complicated grief, post-traumatic stress disorder (PTSD) and depressive disorder was assessed through self-reporting questionnaire, inventory of complicated grief (ICG), PTSD Check List-5 (PCL-5) and Patient Health Questionnaire-9 (PHQ-9). We also included demographic, socioeconomic, health-related variables, and Functional Social Support Questionnaire (FSSQ), which affect the ICG score. Participants were divided into 4 groups based on the experience of psychotherapy or psychiatry clinic service before the accident and mental health support after the disaster. In univariate analysis, these 4 groups showed a significant difference in the mean ICG score (P = 0.020). Participants who received mental health support only after the Sewol ferry accident (group 2) showed a lower mean ICG score than those who received neither psychotherapy or psychiatry clinic service before the disaster nor mental health support after the accident (group 4). There was no significant correlation between the ICG score and other variables except for subjective health status measured 1 month after the disaster (P = 0.005). There was no significant difference in PCL-5 (P = 0.140) and PHQ-9 scores (P = 0.603) among groups, respectively. In conclusion, mental health support significantly reduced the severity of grief only in those participants who had not received any psychotherapy or psychiatry clinic service before the accident.


Optimal prophylactic para-aortic radiotherapy in locally advanced cervical cancer: anatomy-based versus margin-based delineation.
Precise delineation of the para-aortic nodal region is critical for the optimal therapeutic ratio of prophylactic para-aortic radiotherapy. We aimed to evaluate the para-aortic control and patient-reported gastrointestinal toxicity in patients with locally advanced cervical cancer who received anatomy-based or margin-based prophylactic para-aortic radiotherapy. We analyzed 160 patients with locally advanced cervical cancer who received prophylactic extended-field radiotherapy between January 2014 and November 2019 at two tertiary centers. Para-aortic nodal regions were delineated based on the anatomic principle-based atlas or marginal expansion from the aorta and inferior vena cava. The Patient-Reported Outcome version of the Common Terminology Criteria for Adverse Events was used to assess acute gastrointestinal toxicity, and a score of ≥3 was defined as severe gastrointestinal toxicity. Seventy-six (47.5%) and 84 (52.5%) patients received anatomy-based and margin-based prophylactic para-aortic radiotherapy, respectively. The median follow-up was 40.1 months (IQR 25.5-58.9). Para-aortic nodal failures occurred in one (1.3%) patient in the anatomy-based para-aortic radiotherapy group and in one (1.2%) patient in the margin-based para-aortic radiotherapy group (p=1.00). There was no in-field or marginal para-aortic nodal failure. The 3-year para-aortic recurrence-free survival for anatomy-based and margin-based para-aortic radiotherapy was 98.6% and 98.8%, respectively (p=0.94). Patients who received anatomy-based para-aortic radiotherapy reported less severe acute gastrointestinal toxicity than those who received margin-based para-aortic radiotherapy (13.2% vs 29.8%, p=0.01). A comparison of gastrointestinal toxicities showed that patients who received anatomy-based para-aortic radiotherapy reported significantly less severe gastrointestinal toxicity than those who received margin-based para-aortic radiotherapy in terms of frequency of diarrhea (7.9% vs 20.2%, p=0.03), severity of abdominal pain (3.9% vs 14.3%, p=0.03), and interference of abdominal pain (2.6% vs 11.9%, p=0.03). Anatomy-based prophylactic para-aortic radiotherapy achieved excellent para-aortic control and a lower incidence of severe patient-reported gastrointestinal toxicity. These findings suggest that anatomy-based delineation optimizes clinical outcomes of prophylactic para-aortic radiotherapy in locally advanced cervical cancer.


Clinical Relevance of +936 C>T VEGFA and c.233C>T bFGF Polymorphisms in Chronic Lymphocytic Leukemia.
Angiogenesis process contributes to the pathogenesis of B-cell chronic lymphocytic leukemia (B-CLL) being the levels of VEGFA and bFGF higher in patients than in healthy controls. Our aim was to evaluate the implication of angiogenesis factors genetic variants in the predisposition to B-CLL and their association with clinical factors and survival. We performed a population-based case-control study in 224 Spanish B-CLL patients and 476 healthy randomly selected controls to evaluate susceptibility to developing B-CLL. Six polymorphisms were evaluated: rs1109324, rs1547651, rs3025039 (+936 C>T), rs833052 of the VEGFA gene, rs1449683 (c.233C>T) of the bFGF gene and (-710 C>T) of the VEGFR1 gene. The association between clinical parameters and patient outcome was analyzed. Carriers of the CT/TT variants of rs3025039 showed a significant protective effect against developing B-CLL. The CT/TT variants of rs1449683 show a tendency towards the development of the disease and the same variants associated significantly with higher genetic risk and with reduced disease free survival. Moreover, the association persisted in the early-stage disease subgroup. Our study provides evidence of the protective effect of the T/- rs3025039 VEGFA variant against B-CLL development and the association of CT/TT variants of the rs1449683 bFGF gene with genetic risk and an adverse survival.


Controlled unidirectional reflection in cold atoms via the spatial Kramers-Kronig relation.
It is known that the Kramers-Kronig (KK) relation between real and imaginary parts of the optical susceptibility in the frequency domain can also be realized in the space domain, as first proposed in [Nat. Photonics9(7), 436 (2015)10.1038/nphoton.2015.106]. We here study a mechanism to implement spatial KK relations in a cold atomic sample and use it to control unidirectional reflectionless for probe light incident from either the left or right side of the sample at will. In our model, the complex frequency dependent atomic susceptibility is mapped into a spatially dependent one, employing a far-detuned driving field of intensity linearly varied in space. The reflection of an incident light from one side of the sample can then be set to vanish over a specific frequency band directly by changing the driving field parameters, such as its intensity and frequency. Also, by incorporating the Bragg scattering into the spatial KK relation, the reflectivity from the opposite side of the sample, though typically small for realistic atomic densities, can be made to increase to improve the reflectivity contrast. The present scheme bears potentials for all-optical network applications that require controllable unidirectional light propagation.


SNA-60-367 components, new peptide enzyme inhibitors of aromatase: structure of the fatty acid side chain and amino acid sequence by mass spectrometry.
SNA-60-367 components, new peptide enzyme inhibitors of aromatase, were isolated from the culture broth of soil bacterium, Bacillus sp. SNA-60-367. These inhibitors are a family of acylated decapeptides that differ from each other in terms of amino acid composition and the nature of the fatty acid side chain. The structures of the fatty acid moieties were shown to be (3-hydroxy)heptadecanoic acid and (3-hydroxy)hexadecanoic acid that possess normal-, iso- or anteiso-type alkyl groups. The amino acid sequence of the open form of the lactone ring of the acylpeptides is RCO-L-Glu-D-Orn-L(or D)-Tyr3-D-allo-Thr-L-Glu-D-X1 (Ala, Aba or Val)-L-Pro-L-Gln-D(or L)-Tyr-L-X2(10)(Ile or Val)-OH. The lactone ring of SNA-60-367 components is formed between Tyr3 and X2(10).


Microstructure and Mechanical Properties of Dual Scaled NbC/Ti2AlC Reinforced Titanium-Aluminum Composite.
A TiAl composite containing hybrid particles and whisker reinforcements is fabricated by vacuum melting. The results of this study show that the comprehensive mechanical properties and refining effect of the material are best when the content of reinforcement is 1 wt.%, and then the mechanical properties begin to deteriorate as the content increases further. Finely dispersed NbC particles and uniformly dispersed Ti2AlC whiskers are the ideal second phases. The synergistic strengthening effect of NbC particles and in situ Ti2AlC whiskers are key to the improvement of mechanical properties. Compared with the TiAlNb matrix, the fracture stress/strain of the composite at 1073 K is improved from 612 MPa/19.4% to 836 MPa/26.6%; the fracture toughness at room temperature is improved from 18.8 MPa/m2 to 27.4 MPa/m2.


Is stereotactic body radiation therapy an attractive option for unresectable liver metastases? A preliminary report from a phase 2 trial.
To evaluate the feasibility of high-dose stereotactic body radiation therapy (SBRT) in the treatment of unresectable liver metastases. Patients with 1 to 3 liver metastases, with maximum individual tumor diameters less than 6 cm and a Karnofsky Performance Status of at least 70, were enrolled and treated by SBRT on a phase 2 clinical trial. Dose prescription was 75 Gy on 3 consecutive days. SBRT was delivered using the volumetric modulated arc therapy by RapidArc (Varian, Palo Alto, CA) technique. The primary end-point was in-field local control. Secondary end-points were toxicity and survival. Between February 2010 and September 2011, a total of 61 patients with 76 lesions were treated. Among the patients, 21 (34.3%) had stable extrahepatic disease at study entry. The most frequent primary sites were colorectal (45.9%) and breast (18%). Of the patients, 78.7% had 1 lesion, 18.0% had 2 lesions, and 3.3% had 3 lesions. After a median of 12 months (range, 2-26 months), the in-field local response rate was 94%. The median overall survival rate was 19 months, and actuarial survival at 12 months was 83.5%. None of the patients experienced grade 3 or higher acute toxicity. No radiation-induced liver disease was detected. One patient experienced G3 late toxicity at 6 months, resulting from chest wall pain. SBRT for unresectable liver metastases can be considered an effective, safe, and noninvasive therapeutic option, with excellent rates of local control and a low treatment-related toxicity.


Frailty and medical financial hardship among older adults with cancer in the United States.
Little is known about the association between frailty level and medical financial hardship among older adults with cancer. This study aims to describe the prevalence of frailty and to identify its association with medical financial hardship among older cancer survivors in the United States. The National Health Interview Survey (NHIS; 2019-2020) was used to identify older cancer survivors (n = 3,919). Both the five-item (Fatigue, Resistance, Ambulation, Illnesses, and Low weight-for-height) FRAIL and the three-domain (Material, Psychological, and Behavioral) medical financial hardship questions were constructed based on the NHIS questionnaire. Multivariable logistic models were used to identify the frailty level associated with financial hardship and its intensity. A total of 1,583 (40.3%) older individuals with cancer were robust, 1,421 (35.9%) were pre-frail, and 915 (23.8%) were frail. Compared with robust cancer survivors in adjusted analyses, frail cancer survivors were more likely to report issues with material domain (odds ratio (OR) = 3.19, 95%CI: 2.16-4.69; p < 0.001), psychological domain (OR = 1.47, 95%CI: 1.15-1.88; p < 0.001), or behavioral domain (ORs ranged from 2.19 to 2.90, all with p < 0.050), and greater intensities of financial hardship. Both pre-frail and frailty statuses are common in the elderly cancer survivor population, and frail cancer survivors are vulnerable to three-domain financial hardships as compared with robust cancer survivors. Ongoing attention to frailty highlights the healthy aging of older survivors, and efforts to targeted interventions should address geriatric vulnerabilities during cancer survivorship.


The effect of different covalent bond connections and doping on transport properties of planar graphene/MoS2/graphene heterojunctions.
The electronic transport properties of in-plane graphene/MoS2/graphene heterojunctions are studied using density functional theory and the nonequilibrium Green's function method. It is found that different covalent bond connections cause different electron distributions, such as accumulation or depletion, on the contact surface. The C-S structure exhibits more electron accumulation and depletion, indicating that the electrons can easily transfer from MoS2 to graphene. Since the three structures all form covalent or ionic bonds, the tunneling barrier for carriers is very small. The C-S structure exhibits a smaller p-type Schottky barrier, indicating that it has better transport properties than the other two structures. We found that the effective doping method can reduce the Schottky-barrier height (SBH), resulting in smaller contact resistance. Thus, the current-voltage curves of the undoped and doped C-S structures exhibit rectification and approximately linear characteristics under a given bias, which agrees with experimental reports. These results provide insight for designing high-performance devices.


The Resolution of Periodontal Inflammation Promotes Changes in Cytokine Expression in the Intestine and Gingival Tissues of Aged Rats with DSS-Induced Colitis.
Our research aimed to explore how resolving periodontal inflammation impacts cytokine expression in the colons of aged Wistar rats. Research studies involving animals have been conducted to investigate the two-way relationship between periodontitis and inflammatory bowel disease (IBD), where chronic inflammation in either the mouth or intestines can negatively affect the other. We allocated seventeen male Wistar rats aged between 8 and 11 months to one of four groups: (1) ligature-induced periodontitis (LIP) without the resolution of periodontal inflammation (RPI) (LIP; n = 4), (2) LIP + RPI (n = 4), (3) LIP + dextran-sulphate-sodium-induced colitis (DIC) without RPI (n = 4), and LIP + DIC + RPI (n = 5). We performed histopathological and immunological analyses on periodontal and intestinal tissues and analysed cytokine expressions using a Rat Cytokine 23-Plex Immunoassay. Our findings showed that animals with and without DIC who underwent RPI showed significantly lower levels of IL-2, IL-4, IL-5, IL-10, IL-13, IL-17, IL-18, and TNF-α in the intestine compared to those without treatment. The RPI effectively reduced the number of inflammatory cells in the lamina propria and restored the epithelial barrier in the intestine in animals with DIC. The resolution of periodontal inflammation significantly reduced the levels of pro-inflammatory cytokines and chemokines in the intestines of aged rats with and without DSS-induced colitis.


Towards sequence selective DNA binding: design, synthesis and DNA binding studies of novel bis-porphyrin peptidic nanostructures.
A new series of peptidic nanostructures bearing two intercalating moieties was designed and synthesized to achieve selective recognition of DNA sequences. A cationic porphyrin was attached to a glutamic acid side chain and the latter introduced into a peptidic sequence by standard solid-phase peptide synthesis methodology. Conformation of the hydrosoluble peptidic structures bearing two cationic porphyrins was studied by circular dichroism. Using UV-visible spectroscopy and induced circular dichroism, we demonstrate that the compounds are fully intercalated upon binding to double-stranded DNA and that the compounds exhibit a tremendous preference for GC over AT sequences for intercalation.


Effective degrees of nonlinearity in a family of generalized models of two-dimensional turbulence.
We study the small-scale behavior of generalized two-dimensional turbulence governed by a family of model equations, in which the active scalar theta=(-Delta)(alpha/2)psi is advected by the incompressible flow u=(-psi(y),psi(x)). Here psi is the stream function, Delta is the Laplace operator, and alpha is a positive number. The dynamics of this family are characterized by the material conservation of theta, whose variance theta2 is preferentially transferred to high wave numbers (direct transfer). As this transfer proceeds to ever-smaller scales, the gradient nublatheta grows without bound. This growth is due to the stretching term (nablatheta.nabla)u whose "effective degree of nonlinearity" differs from one member of the family to another. This degree depends on the relation between the advecting flow u and the active scalar theta (i.e., on alpha) and is wide ranging, from approximately linear to highly superlinear. Linear dynamics are realized when nablau is a quantity of no smaller scales than theta, so that it is insensitive to the direct transfer of the variance of theta, which is nearly passively advected. This case corresponds to alpha>or=2 , for which the growth of nablatheta is approximately exponential in time and nonaccelerated. For alpha<2, superlinear dynamics are realized as the direct transfer of theta2 entails a growth in nablau, thereby, enhancing the production of nablatheta. This superlinearity reaches the familiar quadratic nonlinearity of three-dimensional turbulence at alpha=1 and surpasses that for alpha<1. The usual vorticity equation (alpha=2) is the border line, where nablau and theta are of the same scale, separating the linear and nonlinear regimes of the small-scale dynamics. We discuss these regimes in detail, with an emphasis on the locality of the direct transfer.


Multiple pathways of capillary permeability.
Morphological and physiological studies indicate multiple routes for transport across capillary endothelium. However, the identification of the morphological counterparts of specific transport processes (or the assignment of specific transport roles to morphologically identifiable pathways) has been only partly achieved: the contribution of endothelial cell membranes to transport of water and small, lipid-insoluble molecules needs to be evaluated. The identification of the "small pore" pathway for water and lipid-insoluble molecules with the intercellular junctions still remains questionable. The contributions to total macromolecular transport of junctions, single vesicles (pinocytosis, cytopempsis), chains of vesicles, and fenestrae are not yet known.


[Pseudotumorous "skip area" in subtotal hepatic steatosis. Echographic and computed tomographic aspects].
In 75 patients ultrasound (US) demonstrated fatty infiltration of the liver with diffuse increased echogenicity except for a solitary hypoechogenic area located in the quadrate lobe. The liver was also followed-up with US, computed tomography (CT), radionuclide scintigraphy, and fine needle biopsy: a skip area unaffected by steatosis was thus demonstrated. This study and further information found in literature allowed the authors to identify the particular US features which lead to a correct interpretation of these findings, which might otherwise be incorrectly diagnosed as suggestive of substitutive lesions (primary or secondary). These features are: 1) the location of skip areas, usually in the IV segment, in close relationship to a portal vessel; 2) their morphology, triangular, or inverted-V shaped; 3) the absence of mass effects upon the hepatic border and/or upon the adjacent vessels; 4) the presence of fatty liver infiltration; 5) the coexistence of a biohumoral pattern significant for diffuse hepatopathy; 6) the lack of change in US patterns during the follow-up.


Comparative studies of the trans-cis photoisomerizations of azobenzene and a bridged azobenzene.
Using density-functional-based molecular dynamics simulations, we have performed comparative studies of the trans-cis isomerizations of azobenzene and bridged azobenzene (B-Ab) 5,6-dihydrodibenzo[c,g][1,2]diazocine induced by nπ* electronic excitation. The quantum yields found in our calculations, 45% for the bridged azobenzene versus 25% for azobenzene, are consistent with the experiment. Both isomerization processes involve two steps: (1) Starting from the trans structure, each molecule moves on its S(1) excited-state potential energy surface, via rotation around the NN bond, to an avoided crossing near the S(1)/S(0) conical intersection, where de-excitation occurs. (2) Subsequently, in the electronic ground state, there is further rotation around the NN bond, accompanied by twisting of the phenyl rings around their CN bonds, until the cis geometry is achieved. Because of its lower symmetry and smaller initial CNNC dihedral angle, the bridged azobenzene has a much shorter lifetime for the S(1) excited state, about 30 fs, as compared to about 400 fs for azobenzene. However, we find that the complete isomerizations have approximately the same time scales. Although the bridging feature in trans-B-Ab does not hinder rotation around the NN bond in step 1, it makes twisting of the two phenyl rings around the CN bonds much slower in step 2.


Genome-Wide Analysis and Identification of 1-Aminocyclopropane-1-Carboxylate Synthase (ACS) Gene Family in Wheat (Triticum aestivum L.).
Ethylene has an important role in regulating plant growth and development as well as responding to adversity stresses. The 1-aminocyclopropane-1-carboxylate synthase (ACS) is the rate-limiting enzyme for ethylene biosynthesis. However, the role of the ACS gene family in wheat has not been examined. In this study, we identified 12 ACS members in wheat. According to their position on the chromosome, we named them TaACS1-TaACS12, which were divided into four subfamilies, and members of the same subfamilies had similar gene structures and protein-conserved motifs. Evolutionary analysis showed that fragment replication was the main reason for the expansion of the TaACS gene family. The spatiotemporal expression specificity showed that most of the members had the highest expression in roots, and all ACS genes contained W box elements that were related to root development, which suggested that the ACS gene family might play an important role in root development. The results of the gene expression profile analysis under stress showed that ACS members could respond to a variety of stresses. Protein interaction prediction showed that there were four types of proteins that could interact with TaACS. We also obtained the targeting relationship between TaACS family members and miRNA. These results provided valuable information for determining the function of the wheat ACS gene, especially under stress.


Aging-associated enzyme human clock-1: substrate-mediated reduction of the diiron center for 5-demethoxyubiquinone hydroxylation.
The mitochondrial membrane-bound enzyme Clock-1 (CLK-1) extends the average longevity of mice and Caenorhabditis elegans, as demonstrated for Δclk-1 constructs for both organisms. Such an apparent impact on aging and the presence of a carboxylate-bridged diiron center in the enzyme inspired this work. We expressed a soluble human CLK-1 (hCLK-1) fusion protein with an N-terminal immunoglobulin binding domain of protein G (GB1). Inclusion of the solubility tag allowed for thorough characterization of the carboxylate-bridged diiron active site of the resulting GB1-hCLK-1 by spectroscopic and kinetic methods. Both UV-visible and Mössbauer experiments provide unambiguous evidence that GB1-hCLK-1 functions as a 5-demethoxyubiquinone-hydroxylase, utilizing its carboxylate-bridged diiron center. The binding of DMQn (n = 0 or 2) to GB1-hCLK-1 mediates reduction of the diiron center by nicotinamide adenine dinucleotide (NADH) and initiates O2 activation for subsequent DMQ hydroxylation. Deployment of DMQ to mediate reduction of the diiron center in GB1-hCLK-1 improves substrate specificity and diminishes consumption of NADH that is uncoupled from substrate oxidation. Both Vmax and kcat/KM for DMQ hydroxylation increase when DMQ0 is replaced by DMQ2 as the substrate, which demonstrates that an isoprenoid side chain enhances enzymatic hydroxylation and improves catalytic efficiency.


Variability of the respiratory response to diazepam.
The authors investigated the respiratory effects of diazepam in 24 healthy volunteers using a modified Read rebreathing circuit. Resting end-tidal CO2 (PETCO2) and the slopes of the ventilatory (VE/PETCO2) and occlusion pressure (P0.1/PETCO2) response to CO2 were measured just prior to and 5, 20, 40, and 60 min after diazepam, 0.1 mg/kg iv. The slope of VE/PETCO2 for all 24 subjects analyzed as a single group was never significantly depressed. The slope of P0.1/PETCO2 for all 24 subjects analyzed as a single group was significantly depressed only at 5 min after diazepam. The resting PETCO2, however, had small but statistically significant increases throughout the 1 h of study. Group or cluster analysis of the slope of P0.1/PETCO2 clearly divided subjects into one group of five subjects, whose P0.1/PETCO2 slope was significantly and consistently augmented for 1 h and a second group of 19 subjects whose P0.1/PETCO2 slope was always less than control for the entire hour. Diazepam may, through effects on pulmonary mechanics and/or the central nervous system, sometimes enhance respiratory responses to CO2 rebreathing. Failure to select for such group effects when studying drug effects by CO2 rebreathing may obscure the severity and duration of respiratory depression that occurs in the majority of individuals. Resting PETCO2 indicated consistent depression of resting minute ventilation by diazepam and may be a more appropriate or sensitive measure of mild or subtle drug-induced respiratory effects.


The association of dietary patterns and weight change in rural older adults 75 years and older.
Little is known about the relationship between weight change and dietary patterns (DP) in older adults, especially in those of advanced age (≥ 75 years). We examined the association of DP with obesity and five-year weight change in community-dwelling older adults (n = 270; mean ± SD age: 78.6 ± 3.9 years). Dietary data were collected from four, random, 24-hour dietary recalls over a 10-month period. Weight change was examined as: (1) 10-pound weight loss; (2) 10-pound weight gain; (3) 10% weight loss; and (4) 10% weight gain. Cluster analysis was used to derive 3 DP ("Health-conscious," "Sweets and dairy," and "Western"). Kaplan-Meier plots and Cox proportional hazards regression models were used. About 39% of participants lost at least 10 pounds during follow up. In the unadjusted model, five-year weight loss was not associated with dietary pattern. However, when stratified by gender, females who were characterized by the Sweets and Dairy and the Western DP were three and two times more likely to lose 10 pounds, respectively, compared to those in the Health-conscious DP (P < 0.05). These observations suggest that it is appropriate to recommend a Health-conscious DP for women 75 years and older who may be at risk for weight loss.


The tendon of flexor pollicis longus: its effects on the muscular control of force and position at the human thumb.
Human flexor pollicis longus tendons obtained at autopsy were subjected to repeated sinusoidal stretching movements. The associated force changes were almost in phase with the movement (force led position by less than 4 degrees), and alterations in the frequency of movement between 2 and 16 Hz had little effect on them. Examination of the thumbs of formalin-fixed cadavers demonstrated that the tendon exerts its force 7.4-8.0 mm in front of the axis of movement of the interphalangeal joint. From a knowledge of the tendon properties and the joint anatomy, one can calculate the changes in tendon length that would accompany any force change at the joint. Equipped with this information one can re-examine the responses to sinusoidal movements of the thumb interphalangeal joints of normal subjects. When the subject exerts a steady flexing force in which stretch reflexes play no important part, measurements of joint stiffness indicate that only a portion of the imposed movement reaches the muscle fibres. The extension of those (visco-elastic) muscle fibres lags behind the extension of the (elastic) tendon. Stretch reflexes contribute to the mechanical resistance of muscle fibres to low frequency (3-5 Hz) displacements, but in the presence of a compliant tendon the length of the muscle fibres does not determine the angle of the joint in any positive way. It is suggested that the compliant tendons of many thumb and finger muscles simplify the neuromuscular control of forces during gripping and handling movements.


Transfer of Borrelia burgdorferi s.s. infection via blood transfusion in a murine model.
Without antibiotic treatment, the Lyme-disease-causing bacterium, Borrelia burgdorferi can be cultured from the peripheral blood of human patients nearly 6 wk post-tick bite. To determine if Lyme disease spirochetes can be transmitted from a spirochetemic donor mouse to a naive recipient during blood transfusion, blood taken from immunocompetent infected mice was transfused into either immunodeficient (SCID) mice, inbred immunocompetent animals (C3H/HeJ), or outbred mice. Nine of 19 (47.7%) immunodeficient mice, 7 of 15 (46.8%) inbred immunocompetent mice, and 6 of 10 (60.0%) outbred mice became infected with B. burgdorferi after transfusion. Our results indicate that it is possible to acquire B. burgdoferi infection via transfused blood in a mouse model of Lyme borreliosis.


Circadian ATP Release in Organotypic Cultures of the Rat Suprachiasmatic Nucleus Is Dependent on P2X7 and P2Y Receptors.
The circadian rhythms in physiological and behavioral functions are driven by a pacemaker located in the suprachiasmatic nucleus (SCN). The rhythms continue in constant darkness and depend on cell-cell communication between neurons and glia. The SCN astrocytes generate also a circadian rhythm in extracellular adenosine 5'-triphosphate (ATP) accumulation, but molecular mechanisms that regulate ATP release are poorly understood. Here, we tested the hypothesis that ATP is released via the plasma membrane purinergic P2X7 receptors (P2X7Rs) and P2Y receptors (P2YRs) which have been previously shown to be expressed in the SCN tissue at transcriptional level. We have investigated this hypothesis using SCN organotypic cultures, primary cultures of SCN astrocytes, ATP bioluminescent assays, immunohistochemistry, patch-clamping, and calcium imaging. We found that extracellular ATP accumulation in organotypic cultures followed a circadian rhythm, with a peak between 24:00 and 04:00 h, and the trough at ~12:00 h. ATP rhythm was inhibited by application of AZ10606120, A438079, and BBG, specific blockers of P2X7R, and potentiated by GW791343, a positive allosteric modulator of this receptor. Double-immunohistochemical staining revealed high expression of the P2X7R protein in astrocytes of SCN slices. PPADS, a non-specific P2 antagonist, and MRS2179, specific P2Y1R antagonist, also abolished ATP rhythm, whereas the specific P2X4R blocker 5-BDBD was not effective. The pannexin-1 hemichannel blocker carbenoxolone displayed a partial inhibitory effect. The P2Y1R agonist MRS2365, and the P2Y2R agonist MRS2768 potentiated ATP release in organotypic cultures and increase intracellular Ca2+ level in cultured astrocytes. Thus, SCN utilizes multiple purinergic receptor systems and pannexin-1 hemichannels to release ATP.


Anxiety, vocalization, and agitation following peripheral nerve block with ropivacaine.
Central nervous system (CNS) and cardiovascular toxicity are potential side effects of local anesthetics. However, ropivacaine has been reported to be less CNS toxic than bupivacaine in human volunteers. We describe three cases of peripheral nerve blockade with ropivacaine that resulted in unusual symptoms of CNS toxicity. In three patients, unexpected behavioral changes occurred during administration of ropivacaine. The patients became extremely agitated, anxious, and screamed, and they did not respond to verbal commands. This case report shows that ropivacaine may cause CNS toxicity that differs from classical signs of local anesthetic-induced toxicity. This effect might be related to the unique structure of ropivacaine, which is formulated in an S-enantiomer preparation. It has been shown that S-enantiomers bind differently to receptors in both the CNS and cardiovascular systems. This property may account for the disinhibition of select neural pathways that are specifically involved in mediation of anxiety and aggression.


T-wave amplitude attenuation/augmentation in patients with changing edematous states: implications for patients with congestive heart failure.
Since peripheral edema impacts the entire electrocardiographic curve, it was hypothesized that it would also affect T waves. The amplitude of T waves were measured in all electrocardiographic leads and a sum (SigmaT) was calculated in 28 patients with and 28 patients without peripheral edema (controls). For patients with peripheral edema, SigmaT on admission was 21.9+/-10.6 mm and SigmaT at peak weight was 8.3+/-6.3 mm (P=.0005). For patients with peripheral edema who subsequently lost weight, SigmaT at peak weight was 7.2+/-6.1 mm and SigmaT at the lowest weight was 14.1+/-12.2 (P=.006). For controls, SigmaT from admission and SigmaT from discharge were 24.4+/-16.9 mm and 24.7+/-15.7 mm (P=.82), respectively. Percent change (Delta%SigmaT) from admission to peak weight correlated with Delta% in weight (r=0.58; P=.001) and Delta% in the sum of QRS complexes (SigmaQRS) (r=0.71; P=.00005). Delta%SigmaT from peak weight to the lowest weight correlated with the corresponding Delta%SigmaQRS (r=0.65; P=.02). Changes in T waves with development and alleviation of peripheral edema mirror the changes shown by the QRS complexes and may be useful in the treatment of patients with congestive heart failure or other edematous states.


Seasonal nitrogen cycling in the bark of field-grown Grey poplar is correlated with meteorological factors and gene expression of bark storage proteins.
Seasonal tree-internal nitrogen cycling is an important strategy for trees to achieve high efficiency in the use of nitrogen (N). Key processes of this N redistribution are autumnal leaf senescence and storage of released N as bark storage proteins (BSP) in perennial tissues. While the regulation of leaf senescence has been intensively analysed in trees, the coordination of the complementary storage processes is still poorly understood. Therefore, we ascertained relationships between physiological-level and molecular-level processes and environmental factors under natural conditions in the bark of Populus x canescens. We analysed amino-N concentrations, total soluble protein concentration and transcript abundances of BSP genes in the bark of field-grown P. x canescens harvested during two annual growth cycles. By correlation analysis and linear modelling, we assessed interactions between biological data and meteorological conditions. Day length correlated with BSP expression, and air temperature correlated strongly with total protein concentration (r = -0.92), gamma-aminobutyric acid (GABA; r = 0.76) and arginine (r = -0.70). GABA and arginine also correlated significantly with total protein concentration and transcript abundances of BSP genes. We conclude that GABA and arginine potentially contribute to adjust storage processes in the bark of poplar trees to seasonal changes in environmental conditions.


The 10 Pillars of Lung Cancer Screening: Rationale and Logistics of a Lung Cancer Screening Program.
On the basis of the National Lung Screening Trial data released in 2011, the U.S. Preventive Services Task Force made lung cancer screening (LCS) with low-dose computed tomography (CT) a public health recommendation in 2013. The Centers for Medicare and Medicaid Services (CMS) currently reimburse LCS for asymptomatic individuals aged 55-77 years who have a tobacco smoking history of at least 30 pack-years and who are either currently smoking or had quit less than 15 years earlier. Commercial insurers reimburse the cost of LCS for individuals aged 55-80 years with the same smoking history. Effective care for the millions of Americans who qualify for LCS requires an organized step-wise approach. The 10-pillar model reflects the elements required to support a successful LCS program: eligibility, education, examination ordering, image acquisition, image review, communication, referral network, quality improvement, reimbursement, and research frontiers. Examination ordering can be coupled with decision support to ensure that only eligible individuals undergo LCS. Communication of results revolves around the Lung Imaging Reporting and Data System (Lung-RADS) from the American College of Radiology. Lung-RADS is a structured decision-oriented reporting system designed to minimize the rate of false-positive screening examination results. With nodule size and morphology as discriminators, Lung-RADS links nodule management pathways to the variety of nodules present on LCS CT studies. Tracking of patient outcomes is facilitated by a CMS-approved national registry maintained by the American College of Radiology. Online supplemental material is available for this article.


[Prognostic value of antibodies against p53 in patients with oral squamous cell carcinoma--five years survival rate].
p53 gene aberrations are the most common genetic changes seen in human carcinogenesis. Frequently, single point mutations are detected, resulting in increased levels of (an aberrant) p53 protein in tumor cells. The cellular protein produced appears to become immunogenic during tumor development, inducing the production of circulating antibodies against p53. For this study, sera from 126 patients with oral squamous cell carcinomas (102 primary tumours and 24 recurrent/secondary tumours) were examined for p53 autoantibodies and their further clinical course was followed up for more than 5 years. 80 sera from internal medicine patients without known or suspected neoplasm served as control. A sandwich ELISA (enzyme linked immuno sorbent assay) designed by Dianova, Hamburg was used to detect p53 autoantibodies. In 18.6 % of the patients with primary oral squamous cell carcinomas, p53 autoantibodies were detected, and also in 50 % of the patients with recurrent or local secondary carcinomas. None of the sera of the control group was positive. Patients with anti-p53 have noticeably poorer prognosis (Log Rank Test, p < 0.005). After a period of 5 years, the overall survival rate of the p53-positive group was 24 % - less than half of that of the p53-negative group with a survival rate of 51 %. : The detection of p53 autoantibodies definitely permits a clearer prognostic assessment, which in turn influences clinical procedures. If p53 autoantibodies are detected in a patient during therapy, the applied therapeutic method should be reconsidered and the patient be more closely observed than other, p53 negative patients.


Imaging the Solvation of a One-Dimensional Solid on the Molecular Scale.
We have observed the inversion of the solvation environment of a one-dimensional solid by low-temperature scanning tunneling microscopy. Adsorption of 3-methoxy-9-diazofluorene on Ag(111) yields highly oriented supramolecular chains, which are then exposed to water molecules. The annealing of dry and water-decorated chains results in diametrically opposed outcomes. While the former simply leads to an increase in chain length and number, the latter results in a complete loss of order and produces water clusters decorated with the organic molecule.


Rationale for choices of occlusal schemes for complete dentures supported by implants.
This review of occlusal considerations for implant-supported complete dentures reflects the majority opinion of authors according to clinical observations and research-documented evidence. Occlusal concepts are presented for the implant-supported complete dentures regarding analysis of loads applied to dental implants, location and number of implants, occlusal materials, and occlusal scheme.


[Prevalence of plasmid-mediated AmpC beta-lactamases in Escherichia coli and Klebsiella spp. isolated in children].
To study the plasmid-mediated AmpC β-lactamases and the genotypes of Escherichia coli and Klebsiella spp. in children. Escherichia coli and Klebsiella spp. of strains were isolated at our division from January to December 2009. Cefoxitin disk diffusion method was used to screen Escherichia coli and Klebsiella spp. for phenotypic AmpC enzyme. Multiple PCR method was adopted to test the genotypes of AmpC enzyme-positive Escherichia coli and Klebsiella spp.strains. Of all Escherichia coli and Klebsiella spp., 65 were insensitive to cefoxitin disk and 17 strains carried DHA type AmpC gene. The prevalence of plasmid-mediated AmpC enzyme in Escherichia coli and Klebsiella spp. was 26.2% (17/65). Among plasmid-mediated AmpC enzyme isolates, 14 (38.9%) Klebsiella pneumoniae strains, 2 (7.7%) Escherichia coli strains and 1 (33.3%) Klebsiella oxytoca strains carried the DHA-1 AmpC gene. The genes of MOX, CIT, DHA, ACC, MIR and FOX were not found in other 48 strains. The identified plasmid-mediated AmpC genes are all of DHA-1 genotype in Escherichia coli and Klebsiella spp. The prevalence of plasmid-mediated AmpC enzyme in Klebsiella pneumoniae isolates is relatively high in children.


Ecological Momentary Assessment of Physical Activity: Validation Study.
Ecological momentary assessment (EMA) may elicit physical activity (PA) estimates that are less prone to bias than traditional self-report measures while providing context. The objective of this study was to examine the convergent validity of EMA-assessed PA compared with accelerometry. The participants self-reported their PA using International Physical Activity Questionnaire (IPAQ) and Behavioral Risk Factor Surveillance System (BRFSS) and wore an accelerometer while completing daily EMAs (delivered through the mobile phone) for 7 days. Weekly summary estimates included sedentary time and moderate-, vigorous-, and moderate-to vigorous-intensity physical activity (MVPA). Spearman coefficients and Lin's concordance correlation coefficients (LCC) examined the linear association and agreement for EMA and the questionnaires as compared with accelerometry. Participants were aged 43.3 (SD 13.1) years, 51.7% (123/238) were African American, 74.8% (178/238) were overweight or obese, and 63.0% (150/238) were low income. The linear associations of EMA and traditional self-reports with accelerometer estimates were statistically significant (P<.05) for sedentary time (EMA: ρ=.16), moderate-intensity PA (EMA: ρ=.29; BRFSS: ρ=.17; IPAQ: ρ=.24), and MVPA (EMA: ρ=.31; BRFSS: ρ=.17; IPAQ: ρ=.20). Only EMA estimates of PA were statistically significant compared with accelerometer for agreement. The mobile EMA showed better correlation and agreement to accelerometer estimates than traditional self-report methods. These findings suggest that mobile EMA may be a practical alternative to accelerometers to assess PA in free-living settings.


Use of incentives to encourage sexually transmissible infection testing amongst sex-on-premises venue patrons.
Incentives have been explored as a strategy for increasing access to sexually transmissible infection (STI) testing. This project sought to trial the offer of free entry to sex-on-premises venues (SOPVs) for venue patrons as an incentive to access sexual health checks. SOPV patrons were offered free entry into venues if they took advantage of sexual health testing at a range of clinics. Patrons were given testing cards from the SOPV that could be exchanged at the time of the clinical consultation for a free entry pass to the SOPV of their choice. Cards collected at clinics and SOPVs were collated. In total, 244 cards were distributed to patrons from four venues over a 6-month period. Ten persons accessed one of the six clinical sites, one person attending twice. Of these persons, five attended two general practices and the remaining five accessed public sexual health clinics. Of these 10 persons, three used their free entry passes to attend an SOPV. Two persons accessed these clinical sites for the first time, one of whom tested reactive for an STI. Another regular attendee also tested reactive. Despite the low uptake, the free entry promotion was inexpensive and could, given sufficient time, be considered an effective incentive. Nonetheless, this study may have contributed to at least two new persons undertaking testing, one of whom was diagnosed with an STI.


Switching anti-TNF-alpha agents: what is the evidence?
The availability of biologic agents targeting tumor necrosis factor (TNF)-alpha represents a significant advance in the management of rheumatoid arthritis. Anti-TNF-alpha therapy has been associated with dramatic improvements in the clinical signs and symptoms of rheumatoid arthritis and has been shown to greatly retard the destructive process that too often characterizes this condition. Although effective and well-tolerated in a substantial proportion of patients, primary and secondary failures of anti-TNF-alpha strategies have been well described, affecting up to one-third to one-half of subjects treated with these agents. Switching from one anti-TNF-alpha agent to a second (or even third) anti-TNF-alpha therapy has emerged as a means of addressing treatment failures with this drug class. This review examines data addressing the practice of switching anti-TNF-alpha agents in the context of initial treatment failure, with a focus on data from peer-reviewed reports.


Infection as a Stroke Trigger.
Background and Purpose- The relationships between different infection types and stroke subtype are not well-characterized. We examined exposure to infections in different organ systems in different time periods before the acute ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Methods- We used the New York State Inpatient Databases and Emergency Department Databases (2006-2013). Validated International Classification of Diseases, Ninth Edition definitions identified index hospitalizations for acute ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage, and emergency department visits and hospitalizations for infection (skin, urinary tract infection, septicemia, abdominal, and respiratory). We used case cross-over analysis with conditional logistic regression to estimate odds ratios (OR) for the association between each infection type during case periods compared with control periods 1 year before. Results- Every infection type was associated with an increased likelihood of acute ischemic stroke. The greatest association was for urinary tract infection, with OR of 5.32 (95% CI, 3.69-7.68) within the 7-day window. The magnitude of association between urinary tract infection and intracerebral hemorrhage was of lesser magnitude, with OR of 1.80 (1.04-3.11) in the 14-day exposure period and OR of 1.54 (1.23-1.94) in the 120-day exposure period. Only respiratory infection was associated with subarachnoid hemorrhage, with OR of 3.67 (1.49-9.04) in the 14-day window and 1.95 (1.44-2.64) in the 120-day window. Conclusions- All infection types were associated with subsequent acute ischemic stroke, with the greatest association for urinary tract infection.


Formation of aminoxy and oxo complexes from the reaction of Nb(NMe2)5 with O2 and the crystal structure of Nb(NEt2)5.
The reaction of Nb(NMe(2))(5) with O(2) gives three complexes: monomeric (Me(2)N)(n)Nb(eta(2)-ONMe(2))(5-n) (n = 3, 4) and dimeric (Me(2)N)(4)Nb(2)[eta(2)-N(Me)CH(2)NMe(2)](2)(mu-O)(2). Nb(NEt(2))(5) was prepared in a mixture of pentane and THF, leading to its purification and characterization by single-crystal X-ray diffraction. Unlike Nb(NMe(2))(5), which adopts a square pyramidal structure, Nb(NEt(2))(5) is a distorted trigonal bipyramid. The reaction of Nb(NEt(2))(5) with O(2) gives an insoluble white solid.


Supplementation with antioxidants and phenolic compounds in ruminant feeding and its effect on dairy products: a systematic review.
Milk and dairy products have great importance in human nutrition related to the presence of different nutrients, including protein, fatty acid profile and bioactive compounds. Dietary supplementation with foods containing these types of compounds may influence the chemical composition of milk and dairy products and hence, potentially, the consumer. Our objective was to summarize the evidence of the effect of supplementation with antioxidants and phenolic compounds in the diets of dairy animals and their effects on milk and dairy products. We conducted a systematic search in the MEDLINE/PubMed database for studies published up until July 2022 that reported on supplementation with antioxidants and phenolic compounds in diets that included plants, herbs, seeds, grains and isolated bioactive compounds of dairy animals such as cows, sheep and goats and their effects on milk and dairy products. Of the 94 studies identified in the search, only 15 met the inclusion criteria and were analyzed. The review revealed that supplementation with false flax cake, sweet grass, Acacia farnesiana, mushroom myceliated grains and sweet grass promoted an effect on the milk lipid profile, whereas supplementation with dried grape pomace and tannin extract promoted an effect on the milk and cheese lipid profiles. In six studies, the addition of Acacia farnesiana, hesperidin or naringin, durum wheat bran, mushroom myceliated grains, dried grape pomace and olive leaves increased the antioxidant activity of milk. In conclusion, supplementation with bioactive compounds had a positive impact which ranged from an increase in antioxidant capacity to a decrease in oxidative biomarkers such as malondialdehyde.


Grapevine (Vitis vinifera L.).
Grapevine (Vitis) is considered to be one of the major fruit crops in the world based on hectares cultivated and economic value. Grapes are used not only for wine but also for fresh fruit, dried fruit, and juice production. Wine is by far the major product of grapes, and the focus of this chapter is on wine grape cultivars. Grapevine cultivars of Vitis vinifera L. have a reputation for producing premium quality wines. These premium quality wines are produced from a small number of cultivars that enjoy a high level of consumer acceptance and are firmly entrenched in the market place because of varietal name branding and the association of certain wine styles and regions with specific cultivars. In light of this situation, grapevine improvement by a transgenic approach is attractive when compared to a classical breeding approach. The transfer of individual traits as single genes with a minimum disruption to the original genome would leave the traditional characteristics of the cultivar intact. However, a reliable transformation system is required for a successful transgenic approach to grapevine improvement. There are three criteria for achieving an efficient Agrobacterium-mediated transformation system: (1) the production of highly regenerative transformable tissue, (2) optimal cocultivation conditions for both grapevine tissue and Agrobacterium, and (3) an efficient selection regime for transgenic plant regeneration. In this chapter, we describe a grapevine transformation system that meets these criteria. We also describe a protocol for the production of transformed roots suitable for functional gene studies and for the production of semi-transgenic grafted plants.


Drug use--problem in pregnancy.
The consumption of drugs during pregnancy considered as a specific medical problem. Drug consumption and drug compliance in pregnancy were analysed in our study. Structured questionnaire and data from mothers were used as principal sources for analysis. Consumption of drugs and compliance with therapy were evaluated in 331 pregnant women, 60% city and 40% rural population, of Region Nitra, Slovakia, after their child birth. Drug's use was confirmed in 75% of pregnant women. The consumption was significantly higher in the first and second pregnancy when compared to the females by in their third or further pregnancies. Medical prescription was the reason of drug use in 89% pregnant women. The number of prescribed drugs similarly as the total consumption was higher in the first and second pregnancies. We noted medical prescribing drug compliance in 70% pregnant women. 16% of pregnant women used anagetic drugs, out of whom 57% on the basis of medical prescription. Adverse drug reactions (gastrointestinal problems and)headache were reported by 15% of pregnant women. In the observed group 6% of women gave birth premature infants (once gemini, once trimini). Two newborns overcomed sepsis. One baby suffered from cheilognatopalatoschisis and two newborns from vitium cordis congenitum. We do not suppose any correlation between child abnormalities and drug consumption during pregnacy. (Tab. 1, Ref. 9.).


GATA factors in vertebrate heart development and disease.
Vertebrate heart formation is dependent upon complex hierarchical gene regulatory networks, which effect both the specification and differentiation of cardiomyocytes and subsequently cardiac morphogenesis. GATA-4, -5 and -6 comprise an evolutionarily conserved subfamily of transcription factors, which are expressed within the precardiac mesoderm from early stages in its specification and continue to be expressed within the adult heart. We review here the functional roles of individual GATA transcription factors in cardiac development, normal homeostasis and disease. We also review the cellular mechanisms employed to regulate the expression and downstream targets of the different GATA factors.


Host-Pathogen Interaction in Fusarium oxysporum Infections: Where Do We Stand?
Fusarium oxysporum, a ubiquitous soilborne pathogen, causes devastating vascular wilt in more than 100 plant species and ranks 5th among the top 10 fungal plant pathogens. It has emerged as a human pathogen, too, causing infections in immune-compromised patients. Therefore, it is important to gain insight into the molecular processes involved in the pathogenesis of this transkingdom pathogen. A complex network comprising interconnected and overlapping signal pathways-mitogen-activated protein kinase signaling pathways, Ras proteins, G-protein signaling components and their downstream pathways, components of the velvet (LaeA/VeA/VelB) complex, and cAMP pathways-is involved in perceiving the host. This network regulates the expression of various pathogenicity genes. However, plants have evolved an elaborate protection system to combat this attack. They, too, possess intricate mechanisms at the molecular level which, once triggered by pathogen attack, transduce signals to activate defense response. This review focuses on understanding and presenting a wholistic picture of the molecular mechanisms of F. oxysporum-host interactions in plant immunity.


Room-Temperature Quantum Ballistic Transport in Monolithic Ultrascaled Al-Ge-Al Nanowire Heterostructures.
Conductance quantization at room temperature is a key requirement for the utilizing of ballistic transport for, e.g., high-performance, low-power dissipating transistors operating at the upper limit of "on"-state conductance or multivalued logic gates. So far, studying conductance quantization has been restricted to high-mobility materials at ultralow temperatures and requires sophisticated nanostructure formation techniques and precise lithography for contact formation. Utilizing a thermally induced exchange reaction between single-crystalline Ge nanowires and Al pads, we achieved monolithic Al-Ge-Al NW heterostructures with ultrasmall Ge segments contacted by self-aligned quasi one-dimensional crystalline Al leads. By integration in electrostatically modulated back-gated field-effect transistors, we demonstrate the first experimental observation of room temperature quantum ballistic transport in Ge, favorable for integration in complementary metal-oxide-semiconductor platform technology.


Using Debates to Teach Evidence-Based Practice in Large Online Courses.
To engage in evidence-based practice (EBP), baccalaureate nursing graduates' competencies must include locating, interpreting, appraising, and applying research findings. Faculty are challenged to find effective ways to incorporate this content in large online courses. Faculty in a thriving college of nursing used interactive debates to teach EBP skills in a large (200+ students) online undergraduate course. Students remain highly engaged while practicing critical thinking, team-work, leadership, delegation, communication skills, and peer evaluation through participation in a series of faculty-facilitated online debates. Meticulous course organization and use of structured debates allows one instructor to teach skills for EBP, while keeping students engaged with each other, the instructor, and the material. Use of debates and the amount of engagement among students and faculty achieved could not be accomplished in a large face-to-face course.


New rules for new drugs: the challenge of AIDS to the regulatory process.
AIDS is systematically changing attitudes and practices regarding the regulation and use of drugs. The complex framework and rigorous research protocols developed by the Food and Drug Administration prior to the 1980s to minimize risk to subjects is shifting in the epidemic's wake to maximize innovation. The FDA has adopted new procedures hastening access to investigational drugs and easing drug importation for personal use, which, in effect, transfers decisions about the benefits and risks of drugs from the agency's staff to patients and their physicians. While the FDA's tilt toward embracing consumer rights may continue in the near future, disappointing results could prompt the agency to reassert its authority in controlling drug policy more restrictively.


DNA-based methodologies for rapid detection, quantification, and species- or strain-level identification of respiratory pathogens (Mycobacteria and Pseudomonads) in metalworking fluids.
Mycobacteria and pseudomonads occurring in modern metalworking fluids (MWF) have been implicated in occupational health hazards as causal agents for hypersensitivity pneumonitis (HP) and other respiratory illnesses in machine workers exposed to these fluids and their aerosols. Unlike the conventional cultural and biochemical methods, which are often slow and ambiguous and detect only culturable cells, DNA-based methods offer a time-saving alternative for reliable detection and identification of both culturable and nonculturable bacteria in MWF and for selective quantification of individual genera of pathogens of interest in these fluids. This is the first report on DNA-based direct detection of mycobacteria and pseudomonads in MWF without culturing. Genus-specific PCR approach was successfully applied for screening of field MWF samples originating from different industrial users for detection of mycobacteria or pseudomonads including both culturable and nonculturable cells. PCR in combination with amplicon DNA sequencing led to the identification of Mycobacterium chelonae, Pseudomonas nitroreducens, and an undefined Pseudomonas species from these fluids. Genome fingerprinting by pulsed-field gel electrophoresis (PFGE) on Mycobacterium isolates further showed that the isolates represented three strains of M. chelonae although the possibility of one of the strains being clonal with M. immunogenum cannot be excluded. In parallel efforts, a quantitative competitive PCR method developed based on the Pseudomonas-specific PCR was applied to quantify total P. fluorescens cells in contaminated metalworking fluid and MWF aerosol without culturing. The DNA-based protocols developed in this study will allow rapid screening of field MWF samples for the presence of both culturable and nonculturable cells and thus facilitate effective fluid management and timely exposure assessment.


Monocytes and impaired leukocyte migration inhibitory factor production in head and neck squamous carcinoma.
Impaired cell-mediated immunity has been consistently associated with head and neck squamous carcinoma (HNSC). Previous work has implicated monocytes in this impairment. The present study shows that in a subgroup of untreated patients with advanced HNSC, monocytes are responsible for impaired in vitro lymphokine (leukocyte migration inhibitory factor) production. In view of recent studies suggesting interactions between lymphokines and monocytes in the immune response, the present findings may be relevant to future immunotherapeutic approaches.


A randomized trial in the investigation of anxiety and depression in patients with coronavirus disease 2019 (COVID-19).
In March 2020, the World Health Organization (WHO) declared COVID-19 a public health emergency of international concern. A small proportion of patients infected with COVID-19 go on to develop pneumonia. We speculated that COVID-19 may be likely to result in psychological disorders such as anxiety and depression. In this study, we conducted an investigation of anxiety and depression in patients with COVID-19. Sixty-five COVID-19 patients were randomly enrolled into this study. Anxiety and depression among participants were measured through the completion of anonymous Chinese-language Zung self-rating anxiety scale and self-rating depression scale questionnaires. Data were analyzed using independent samples t-tests, Mann-Whitney U-tests, and χ2 tests. The questionnaire results showed that 26.15% and 41.54% of participants suffered from anxiety and depression, respectively, although there was no significantly statistical difference between the proportions of COVID-19 patients with anxiety and depression. Statistically significant differences in employment status, partial pressure of oxygen, and corticosteroid application existed between moderate- and severe COVID-19 patients (P<0.05). In particular, the partial pressure of oxygen was significantly lower in severe COVID-19 patients than in their moderate counter parts (71.31±23.54 vs. 101.06±34.43, U=156, P=0.006). Total lymphocytes was lower in severe group than in moderate group [1.659±0.643 vs. 0.745 (0.645, 0.928), U=109, P=0.000]. Also, a higher proportion of female than male patients had anxiety (χ2=5.388, P=0.02). COVID-19 patients who received antiviral medications also displayed a higher rate of anxiety (χ2=4.481, P=0.034). Total lymphocytes between the non-anxiety and anxiety had statistical difference (U=321, P=0.019). Meanwhile, total lymphocytes between the non-depression and depression also had statistical difference (U=389.5, P=0.01). Among patients with COVID-19, females and those treated with antiviral medications were more likely to experience anxiety. In addition, our findings reflected the effect of anxiety and depression on immune system.


Majocchi's Granuloma after Topical Corticosteroids Therapy.
Majocchi's granuloma (MG) is an unusual but not rare dermatophyte infection of dermal and subcutaneous tissues. Dermatophytes usually result in the infections of hair, epidermis, and nail, and are rarely involved in deep cutaneous and subcutaneous tissues. Now it is considered that MG includes two forms: one is a small perifollicular papular form and the other is a deep subcutaneous nodular form; the front one mainly occurs in healthy individuals and the latter one usually presents in immunocompromised hosts. The clinical manifestations of MG are many and varied, except the common presentations of erythema, papule and nodules, and Kaposi sarcoma-like and molluscum-like lesions have been reported in literatures (Kim et al. (2011), Bord et al. (2007), and Lillis et al. (2010)). This characteristic induces the difficulty of diagnosis, and thus it is so important and necessary to make direct microscopical and histological examinations. We describe a case of MG over the face in a patient who had been treated with topical corticosteroids over a long time.


The heat shock factor gene family in Salix suchowensis: a genome-wide survey and expression profiling during development and abiotic stresses.
Heat shock transcription factors (Hsfs), which act as important transcriptional regulatory proteins, play crucial roles in plant developmental processes, and stress responses. Recently, the genome of the shrub willow Salix suchowensis was fully sequenced. In this study, a total of 27 non-redundant Hsf genes were identified from the S. suchowensis genome. Phylogenetic analysis revealed that the members of the SsuHsf family can be divided into three groups (class A, B, and C) based on their structural characteristics. Promoter analysis indicated that the SsuHsfs promoters included various cis-acting elements related to hormone and/or stress responses. Furthermore, the expression profiles of 27 SsuHsfs were analyzed in different tissues and under various stresses (heat, drought, salt, and ABA treatment) using RT-PCR. The results demonstrated that the SsuHsfs were involved in abiotic stress responses. Our results contribute to a better understanding of the complexity of the SsuHsf gene family, and will facilitate functional characterization in future studies.


Preparing Platelet-Rich Plasma with Whole Blood Harvested Intraoperatively During Spinal Fusion.
BACKGROUND Platelet-rich plasma (PRP) has gained growing popularity in use in spinal fusion procedures in the last decade. Substantial intraoperative blood loss is frequently accompanied with spinal fusion, and it is unknown whether blood harvested intraoperatively qualifies for PRP preparation. MATERIAL AND METHODS Whole blood was harvested intraoperatively and venous blood was collected by venipuncture. Then, we investigated the platelet concentrations in whole blood and PRP, the concentration of growth factors in PRP, and the effects of PRP on the proliferation and viability of human bone marrow-derived mesenchymal stem cells (HBMSCs). RESULTS Our results revealed that intraoperatively harvested whole blood and whole blood collected by venipuncture were similar in platelet concentration. In addition, PRP formulations prepared from both kinds of whole blood were similar in concentration of platelet and growth factors. Additional analysis showed that the similar concentrations of growth factors resulted from the similar platelet concentrations of whole blood and PRP between the two groups. Moreover, these two kinds of PRP formulations had similar effects on promoting cell proliferation and enhancing cell viability. CONCLUSIONS Therefore, intraoperatively harvested whole blood may be a potential option for preparing PRP spinal fusion.


Adrenocortical involvement during diverse stress in soft-shelled turtle Lissemys p. punctata Bonnoterre.
Adrenocortical responses to diverse stressful situations (dehydration, formaldehyde treatment and salt loading) were studied in the adult female soft-shelled turtle, Lissenmys p. punctata. Dehydration, formaldehyde treatment (formalin, 1%: 0.1 ml/100 g body weight daily) or salt loading (NaCl, 1%: 0.1 ml/100 g body weight daily) treatments consecutively for 7 days caused hypertrophy of the adrenocortical cells with their nuclear diameter increased, and depletions of adrenal cholesterol and ascorbic acid concentrations followed by decreased acid phosphatase and alkaline phosphatase activities in turtles. Corticosterone levels were elevated in both the adrenal gland and serum of turtles after dehydration and formalin stress, but the hormone level remained unaltered after salt loading in turtles. The results suggest active involvement of adrenal cortex in stress for homeostasis in Lissemys turtles.


[Expression of microRNA-221 and IL-17 in papillary thyroid carcinoma and correlation with clinicopathologic features].
Objective: To study the expression of microRNA-221(miR-221) and IL-17 in papillary thyroid carcinoma (PTC) and their roles in the carcinogenesis of PTC. Methods: Real-time RT-PCR, Western blot and immunohistochemistry (IHC) were used to detect the expression of miR-221 and IL-17 in 40 cases of PTC, 20 adjacent normal thyroid tissues and 20 cases of nodular goiter, and the correlation with clinicopathologic features was analyzed. Results: (1)The expression level of miR-221 was significantly higher in PTC compared with nodular goiter and adjacent normal thyroid tissue (P<0.05), but not between the latter two (P>0.05). The expression of miR-221 was related to TNM staging, capsular invasion and lymph node metastasis (P<0.05) but not to patients' age, sex, tumor size, multifocality, tumor spread and vascular invasion.(2)Real-time RT-PCR and Western blot showed that higher levels of IL-17 mRNA and IL-17 protein in PTC than nodular goiter and adjacent normal thyroid tissue (P<0.05), but not between the latter two (P>0.05). IHC assay showed positive expression of IL-17 in PTC but not in nodular goiter and adjacent normal thyroid tissue. IL-17 expression was related to TNM staging, capsular invasion and lymph node metastasis, but not to patients' age, sex, tumor size, tumor spread and vascular invasion.(3) Expression analysis revealed a significant correlation between the miR-221 and IL-17 expression (r=0.524, P=0.001). Conclusions: The expressions of miR-221 and IL-17 are significantly higher and positively correlated in PTC, suggesting that miR-221 may regulate IL-17 expression by interacting with a variety of cytokines and inflammatory cells to participate in the development of PTC. miR-221 may be a potential novel prognostic indicator and therapeutic target for PTC.


Human tryptophanyl-tRNA synthetase binds with heme to enhance its aminoacylation activity.
Mammalian tryptophanyl-tRNA synthetases (TrpRSs) are Zn2+-binding proteins that catalyze the aminoacylation of tRNATrp. The cellular expression level of human TrpRS is highly upregulated by interferon-gamma (IFN-gamma). In this study, a heme biosynthesis inhibitor, succinylacetone (SA), was found to inhibit cellular TrpRS activity in IFN-gamma-activated cells without affecting TrpRS protein expression. In addition, supplementation of lysates from the SA-treated cells with hemin fully restored TrpRS activity to control levels. Biochemical analyses using purified TrpRS demonstrated that heme can interact strongly with Zn2+-depleted human full-length TrpRS with a stoichiometric heme:protein ratio of 1:1 to enhance the aminoacylation activity significantly. In contrast, the Zn2+-bound form of TrpRS did not bind heme. Further studies using site-directed mutagenesis clarified that the Zn2+-unbound human H130R mutant cannot bind heme. These results provide the first evidence of the involvement of heme in regulation of TrpRS aminoacylation activity. The regulation mechanism and its physiological roles are discussed.


AlCl3-catalyzed tandem acetylation of hydroarylated [60]fullerenes.
The AlCl3-catalyzed acetylation of 1,2-hydrophenylated [60]fullerenes, HC60-Ar, proceeded via a sequential manner involving the acetylation at the hydrogenated fullerene carbon, the following intramolecular cyclization with the adjacent aryl group, the facile loss of water, and the second acetylation of the generated indenylidene double bond. However, the similar reaction of the hydrobiphenylated analogue brought about the normal acetylation at the terminal aromatic ring prior to the same sequential reactions as did hydrophenylated fullerenes.


Cultivating our humanity: A systematic review of care farming & traumatic grief.
Traumatic grief is a complex biopsychosocial experience, frequently (and contentiously) medicalized in the Western world. Care farming is an increasingly popular place-based intervention utilizing agricultural settings to care for vulnerable groups. We sought to establish the extent of care farming in relation to traumatic grief and query the potential of care farming as an intervention for this specific population. A systematic review highlights that whilst understudied, the success of care farming as an intervention for other populations experiencing psychological distress demonstrates the huge potential for care farming as a means to therapeutically engage with individuals experiencing traumatic grief.


Natural History of Type II Autosomal Dominant Osteopetrosis: A Single Center Retrospective Study.
Autosomal dominant osteopetrosis II (ADO II, MIM166600) is a sclerosing bone disorder caused by CLCN7 mutation. The main clinical characteristics include minor trauma-related fracture and hip osteoarthritis, whereas cranial nerve palsy and bone marrow failure rarely develop. Although it is generally believed that ADO II has a relatively benign course, the natural course of the disease in Chinese patients remains unclear. Thirty-six patients diagnosed with ADO II in Shanghai Jiao Tong University Affiliated Sixth People's Hospital from 2008 to 2021 were studied retrospectively. Among them, 15 patients were followed for an average of 6.3 years (1-14 years). In this study, minor trauma-related fractures of the limb were the most typical clinical manifestations. Visual loss (1/36) and bone marrow failure (2/36), was rare in this study. The condition of ADO II seems to be stable in most patients. There were no correlations between markedly elevated bone mineral density (BMD) and minor trauma-related fractures. In total, 21 diseases causing mutations were detected. Among them, the mutation c.2299C>T (p.Arg767Trp) was the most common (16.67%), and mutation c.937G>A [p.(Glu313Lys)] was associated with severe fractures, haematological defects and cranial palsy. Minor trauma-related fracture is the most typical clinical manifestation of ADO II and always occurs in. The mutation c.2299C>T (p.Arg767Trp) is in general a relatively common variant, while the mutation c.937G>A [p.(Glu313Lys)] seems to be associated with severe phenotype. In our study, ADO II seems to remain stable over time.


Highly uniform growth of monolayer graphene by chemical vapor deposition on Cu-Ag alloy catalysts.
One of the major challenges for the practical application of graphene is the large scale synthesis of uniform films with high quality at lower temperature. Here, we demonstrate the use of Ag-plated Cu substrates in the synthesis of high-quality graphene films via chemical vapor deposition (CVD) of methane gas at temperatures as low as 900 °C. Various experimental analyses show that the plated Ag diffuses into Cu to form a uniform Cu-Ag alloy that suppresses the formation of multilayer nucleation and decreases the activation energy of precursor formation, leading to a lower synthesis temperature with enhanced monolayer coverage. In addition, we also observed an unusual Ag-assisted abnormal grain growth of Cu into the cube texture with larger grain sizes and reduced grain boundaries, which is believed to provide the homogeneous environment needed for uniform graphene growth.


Decoupling: what is it and does it really help increase consent to organ donation?
Although the notion of decoupling is simple and potentially controllable by organ donation requestors, evidence to date of its potential has been inconsistent. The impact of the timing of requests was analyzed using data from a study of organ donor-eligible patients and their families (N = 420), involving 9 trauma hospitals located in southwest Pennsylvania and northeast Ohio. In-depth interviews where conducted with family members, healthcare professionals, and organ procurement organization staff involved in the process. Only a weak effect was found for the impact of timing on the decision using a bivariate, correlational analysis. Moreover, we found that raising the issue before rather than after the pronouncement of death was most strongly associated with consent to donation. This effect disappeared after examining decoupling in relation to other factors. However, active consideration of the patient's donation wishes and a clear understanding of the families' initial inclination toward donation were associated with consent to organ donation.


Sex differences in distribution and identity of aromatase gene expressing cells in the young adult rat brain.
Aromatase catalyzes the synthesis of estrogens from androgens. Knowledge on its regional expression in the brain is of relevance to the behavioral implications of these hormones that might be linked to sex differences in mental health. The present study investigated the distribution of cells expressing the aromatase coding gene (Cyp19a1) in limbic regions of young adult rats of both sexes, and characterized the cell types expressing this gene. Cyp19a1 mRNA was mapped using fluorescent in situ hybridization (FISH). Co-expression with specific cell markers was assessed with double FISH; glutamatergic, gamma-aminobutyric acid (GABA)-ergic, glial, monoaminergic, as well as interneuron markers were tested. Automated quantification of the cells expressing the different genes was performed using CellProfiler. Sex differences in the number of cells expressing Cyp19a1 was tested non-parametrically, with the effect size indicated by the rank-biserial correlation. FDR correction for multiple testing was applied. In the male brain, the highest percentage of Cyp19a1+ cells was found in the medial amygdaloid nucleus and the bed nucleus of stria terminalis, followed by the medial preoptic area, the CA2/3 fields of the hippocampus, the cortical amygdaloid nucleus and the amygdalo-hippocampal area. A lower percentage was detected in the caudate putamen, the nucleus accumbens, and the ventromedial hypothalamus. In females, the distribution of Cyp19a1+ cells was similar but at a lower percentage. In most regions, the majority of Cyp19a1+ cells were GABAergic, except for in the cortical-like regions of the amygdala where most were glutamatergic. A smaller fraction of cells co-expressed Slc1a3, suggesting expression of Cyp19a1 in astrocytes; monoaminergic markers were not co-expressed. Moreover, sex differences were detected regarding the identity of Cyp19a1+ cells. Females show overall a lower number of cells expressing Cyp19a1 in the limbic brain. In both sexes, aromatase is expressed in a region-specific manner in GABAergic and glutamatergic neurons. These findings call for investigations of the relevance of sex-specific and region-dependent expression of Cyp19a1 in the limbic brain to sex differences in behavior and mental health.


L-Ascorbic acid and D-isoascorbic acid in a common cold survey.
In a survey of double-bind design, 3 groups of approximately 70 student volunteers took 1 g L-ascorbic acid, 1 g D-isoascorbic acid, or placebo tablets every day for 15 weeks and the incidence and duration of colds were recorded. The group taking D-isoascrobic acid suffered 34% fewer colds than the other two groups; the results were also analyzed in relation to the sex and smoking habits of the volunteers. The rationale for investigating D-isoascorbic acid, an isomer of L-ascorbic acid which has limited antiscorbutic activity, is discussed.


Eluxadoline for the treatment of diarrhoea-predominant irritable bowel syndrome.
Irritable bowel syndrome (IBS) treatment is challenging physicians because of its multifactorial physiopathology. In particular, abdominal pain and diarrhea management lack one unique effective pharmacological remedy. Opioid receptors, present in the central nervous system (CNS) and the enteric nervous system (ENS), are involved in visceral sensitivity and gastrointestinal motility control. To date only a few opioid receptor modulators are currently in use for the treatment of IBS but with dosage limitations due to the early development of severe constipation. In this drug evaluation manuscript we review the irritable bowel syndrome therapeutic needs and chemistry, pharmacokinetics and -dynamics, clinical study results with the new opioid receptor ligand eluxadoline for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D). Eluxadoline shows a peculiar pharmacological profile with μ-opioid agonism and δ-opioid antagonism actions. Its efficacy over placebo for the treatment of abdominal pain and diarrhea in IBS-D has been demonstrated in short- and long-term clinical studies in humans. Its safety has been evaluated in the same studies. Interestingly, eluxadoline showed a low rate of constipation development in IBS patients in comparison with known effects of other opioid receptor modulators. Patients with a history of acute pancreatitis should not be treated with eluxadoline.


[Difficulty in Preoperative Diagnosis of Residual Gastric Cancer after Distal Gastrectomy for Duodenal Ulcer].
A 67-year-old man underwent distal gastrectomy via the Billroth Ⅱ method (B-Ⅱ) for a duodenal ulcer. He presented with appetite loss and nausea in May 2014. Gastrointestinal endoscopy revealed wall thickness around gastrojejunostomy and the gastric mucosal fold. Biopsy and re-biopsy revealed a group 2 tumor. Laparotomy for diagnosis was performed because of stenosis and tumor progression. Intraoperative frozen section examination revealed adenocarcinoma in the lymph nodes of the jejunum. Residual gastrectomy with reconstruction using the Roux-en-Y method was performed for residual gastric cancer. Histopathological findings revealed pT4a, pN0, pM1 for the tumor in the lymph nodes of the jejunum, pStage Ⅳ. A distorted gastrojejunostomy site and the presence of anastomotic strictures are important for the rapid diagnosis of residual gastric cancer.


Oxidant-mediated cAMP response element binding protein activation: calcium regulation and role in apoptosis of lung epithelial cells.
Oxidant stress-mediated regulation of extracellular signal-regulated kinases (ERK1/2) is linked to pathologic outcomes in lung epithelium, yet a role for Ca2+ and Ca2+/cAMP-response element binding protein (CREB) in ERK1/2 signaling has not been defined. In this study, we tested the hypotheses that oxidants induce Ca2+-mediated phosphorylation of ERK and CREB, and that CREB is required for oxidant-induced proliferation and apoptosis. H2O2 initiated an influx of extracellular Ca2+ that was required for phosphorylation of both ERK and CREB in C10 lung epithelial cells. H2O2-mediated CREB phosphorylation was sensitive to MEK inhibition, suggesting that crosstalk between Ca2+, ERK, and CREB signaling pathways contributes to the oxidant-induced response. Reduction of CREB activity, using a dominant-negative CREB construct, inhibited c-fos steady-state mRNA levels, but unexpectedly enhanced bcl-2 steady-state mRNA levels after H2O2 exposure. Whereas inhibition of CREB activity had no detectable effect on H2O2 stimulation of cell cycle, loss of CREB activity significantly reduced the number of cells undergoing apoptosis. These data support a novel communication between Ca2+-ERK1/2 and CREB elicited by H2O2, and further provide evidence that CREB is an important regulator of apoptosis in oxidant-mediated responses of lung epithelial cells.