Osteocalcin expression by circulating endothelial progenitor cells in patients with coronary atherosclerosis.
This study was designed to test whether patients with coronary atherosclerosis have increases in circulating endothelial progenitor cells (EPCs) expressing an osteogenic phenotype. Increasing evidence indicates a link between bone and the vasculature, and bone marrow and circulating osteogenic cells have been identified by staining for the osteoblastic marker, osteocalcin (OCN). Endothelial progenitor cells contribute to vascular repair, but repair of vascular injury may result in calcification. Using cell surface markers (CD34, CD133, kinase insert domain receptor [KDR]) to identify EPCs, we examined whether patients with coronary atherosclerosis had increases in the percentage of EPCs expressing OCN. We studied 72 patients undergoing invasive coronary assessment: control patients (normal coronary arteries and no endothelial dysfunction, n = 21) versus 2 groups with coronary atherosclerosis-early coronary atherosclerosis (normal coronary arteries but with endothelial dysfunction, n = 22) and late coronary atherosclerosis (severe, multivessel coronary artery disease, n = 29). Peripheral blood mononuclear cells were analyzed using flow cytometry. Compared with control patients, patients with early or late coronary atherosclerosis had significant increases (approximately 2-fold) in the percentage of CD34+/KDR+ and CD34+/CD133+/KDR+ cells costaining for OCN. Even larger increases were noted in the early and late coronary atherosclerosis patients in the percentage of CD34+/CD133-/KDR+ cells costaining for OCN (5- and 2-fold, p < 0.001 and 0.05, respectively). A higher percentage of EPCs express OCN in patients with coronary atherosclerosis compared with subjects with normal endothelial function and no structural coronary artery disease. These findings have potential implications for the mechanisms of vascular calcification and for the development of novel markers for coronary atherosclerosis.


Increasing social interactions of severely handicapped autistic children.
A peer-initiation training procedure was implemented across multiple peer trainers to investigate social interactions between severely withdrawn autistic children and their nonhandicapped peers. For one subject, substantial increases in spontaneous interactions with training and nontraining peers occurred after the peer-initiation procedure was applied across two training exemplars. Spontaneous social interactions continued even after the training procedure was removed. Although experimental control was established with the second subject during training, spontaneous interactions during nontraining periods were primarily with training peers. The results contribute to an emerging data base on the social interactions of autistic and severely withdrawn handicapped children and on peer-initiation training procedures.


Thawing of fresh-frozen plasma at 45 degrees C versus 37 degrees C. Comparison using satellite packs of the same donor units.
Packs of fresh-frozen plasma (FFP) from the same donor units were thawed at 37 degrees C and at 45 degrees C in order to determine the suitability of the higher temperature for thawing FFP. Measurements of prothrombin time, activated partial thromboplastin time, fibrinogen concentration, and Factor VIII activity showed no significant differences between the temperatures. Thawing time at 45 degrees C was approximately half that at 37 degrees C. The protocol for manipulation and inspection of the FFP was an important determinant of the thawing time, but did not appear to affect coagulation. FFP can safely be thawed in a 45 degrees C water bath if it is removed before thawing is complete.


Rheumatoid arthritis and the risk of major cardiometabolic diseases: a Mendelian randomization study.
Rheumatoid arthritis (RA) is suggested to be implicated in the development of cardiometabolic diseases. We conducted a Mendelian randomization (MR) study to assess potential causality for associations of RA with the risk of cardiometabolic diseases, including type 2 diabetes (T2D), coronary artery disease (CAD), and ischaemic stroke. Seventy independent single-nucleotide polymorphisms (SNPs) associated with RA were identified as instrumental variables from a genome-wide association study (GWAS) of 58 284 European subjects. Summary-level data for the associations of the 70 genetic variants with T2D, CAD, and ischaemic stroke were taken from three GWASs with a total of 1 529 131 participants. Inverse-variance weighted (IVW) MR was used in the main analyses. The main IVW MR analysis showed that genetically determined RA was associated with higher risks of T2D [odds ratio (OR): 1.04, 95% confidence interval (CI) 1.02-1.05; p < 0.001] and CAD (OR: 1.02, 95% CI 1.00-1.03; p = 0.012), but not ischaemic stroke (OR: 1.00, 95% CI 0.99-1.02; p = 0.961). Sensitivity analyses with multiple MR methods confirmed these associations. MR-Egger regression showed no evidence of pleiotropy in the association between genetically determined RA and the risk of T2D, CAD, and ischaemic stroke. Leave-one-out sensitivity analysis showed that the association between genetically determined RA and the risk of T2D, CAD, and ischaemic stroke was not driven by any individual SNP. Genetically determined RA was associated with increased risks of T2D and CAD, suggesting that RA plays a crucial role in the pathogenesis of T2D and CAD.


DARS2 overexpression is associated with PET/CT metabolic parameters and affects glycolytic activity in lung adenocarcinoma.
This study investigated the correlation between the expression of DARS2 and metabolic parameters of 18F-FDG PET/CT, and explored the potential mechanisms of DARS2 affecting the proliferation and glycolysis of lung adenocarcinoma (LUAD) cells. This study used genomics and proteomics to analyze the difference in DARS2 expression between LUAD samples and control samples. An analysis of 62 patients with LUAD who underwent 18F-FDG PET/CT examinations before surgery was conducted retrospectively. The correlation between DARS2 expression and PET/CT metabolic parameters, including SUVmax, SUVmean, MTV, and TLG, was examined by Spearman correlation analysis. In addition, the molecular mechanism of interfering with DARS2 expression in inhibiting LUAD cell proliferation and glycolysis was analyzed through in vitro cell experiments. DARS2 expression was significantly higher in LUAD samples than in control samples (p < 0.001). DARS2 has high specificity (98.4%) and sensitivity (95.2%) in the diagnosis of LUAD. DARS2 expression was positively correlated with SUVmax, SUVmean, and TLG (p < 0.001). At the same time, the sensitivity and specificity of SUVmax in predicting DARS2 overexpression in LUAD were 88.9% and 65.9%, respectively. In vitro cell experiments have shown that interfering with DARS2 expression can inhibit the proliferation and migration of LUAD cells, promote cell apoptosis, and inhibit the glycolytic activity of tumor cells by inhibiting the expression of glycolytic related genes SLC2A1, GPI, ALDOA, and PGAM1. Overexpression of DARS2 is associated with metabolic parameters on 18F-FDG PET/CT, which can improve LUAD diagnosis accuracy. DARS2 may be a useful biomarker to diagnose, prognosis, and target treatment of LUAD patients.


Traumatic aortic disruption: false positive diagnosis on transesophageal echocardiography.
A case is described in which there was a high index of suspicion for traumatic aortic disruption. Because angiography was equivocal, transesophageal echocardiography was performed, and interpreted as showing a noncircumferential aortic tear. At thoracotomy, however, no tear was seen. The false positive interpretation was caused by a crescent-shaped atherosclerotic plaque.


Redox Reaction in Ti-Mn Redox Flow Battery Studied by X-ray Absorption Spectroscopy.
We performed X-ray absorption studies for the electrolytes of a Ti-Mn redox flow battery (RFB) to understand the redox reaction of the Ti/Mn ions and formation of precipitates in charged catholyte, because suppression of the disproportionation reaction is a key to improve the cyclability of Ti-Mn RFB and enhance the energy density. Hard X-ray absorption spectroscopy with a high transmittance and soft X-ray absorption spectroscopy to directly observe the 3d orbitals were complementarily employed. Moreover, the Ti/Mn 3d electronic structure for each precipitate and solution in the charged catholyte was investigated by using scanning transmission X-ray microscopy: the valence of Mn in the precipitate is mostly attributed to 4+, and the solution includes only Mn2+ . This charge disproportionation reaction should occur after the Mn ions in the catholyte should be oxidized from Mn2+ to Mn3+ by charge.


Direct Relationship between Interleukin-10 Gene Polymorphism and Hepatocellular Carcinoma Complicated by Direct Acting Antiviral Treatment of Hepatitis C Virus.
This study aimed to assess the correlation between the genotyping of interleukin-10 (IL-10 polymorphism rs 1800871) and the incidence hepatocellular carcinoma (HCC) among patients with hepatitis C virus (HCV) treated with direct acting antivirals (DAAs). For 200 patients with HCV infection who completed DAA treatment and followed up for 1 year, IL-10 polymorphism SNP(-819) rs 1800871 analysis was conducted via real time polymerase chain reaction. During the follow-up period, 100 patients who developed HCC were selected and compared with 100 patients who did not develop any complications. The studied patients were divided into two groups according to the incidence of complications after completion of DAA treatments. During the follow-up, 100 patients with HCV infection who developed HCC were selected and compared with 100 patients with HCV infection who did not develop any complications (positive control group). For the HCC group (n = 100), the mean age was 58.1 ± 6.4 years, with 92.7% being male and 7.3% being female; 91% had cirrhosis, 10% had lymphadenitis, 75% had splenomegaly, and 17% had ascites. In the positive control group (n = 100), mean age was 46.3 ± 9.4 years, with 68% being male and 32% being female; 20% had cirrhosis, 12% had splenomegaly, and 4.2% had ascites. The results demonstrated that sofosbuvir (SOF) + daclatasvir + ribavirin regimen was the most prevalent drug treatment for patients with HCC (72%), while SOF + Simeprevir was the most safe treatment for HCV infection among patients with HCC (2%). CT genotype was the most common genotype in the HCC group (56%), among different drug regimen (67.8%). T allele was the most prevalent in HCC group (61%), while the C allele was the least prevalent (39%). IL-10 genotyping may help in selecting the safest and most accurate drug regimen according to the safest genotype response relationship and follow-up of genotype resistance.


Control of ventilation in the hypercapnic skate Raja ocellata: I. Blood and extradural fluid.
In order to study the role of CO2 and acid-base status in contributing to ventilatory drive, skate were exposed to normoxic hypercapnia (PICO2 = 7.5 Torr) under conditions where the primary O2 drive would remain unaltered. Blood O2 transport was markedly insensitive to CO2, with no Root effect and only a small Bohr effect. Red blood cell pHi was not preferentially regulated, and there was no evidence of RBC swelling or nucleoside triphosphate adjustment. Although there were no changes in arterial O2 levels during hypercapnia, ventilation immediately increased 2.7-fold through large changes in stroke volume and small changes in frequency, and declined only slightly through 24-48 h. PaCO2 equilibrated rapidly with PICO2, driving down arterial pHa, which was 65% corrected through HCO3- accumulation by 24 h. In contrast, the extradural fluid outside the brain equilibrated only very slowly, and was clearly not involved in the ventilatory stimulation. Increased ventilation during hypercapnia may be related to depression in pHa.


Development as a dynamic system.
Development is about creating something more from something less, for example, a walking and talking toddler from a helpless infant. One current theoretical framework views the developmental process as a change within a complex dynamic system. Development is seen as the emergent product of many decentralized and local interactions that occur in real time. We examine how studying the multicausality of real-time processes could be the key to understanding change over developmental time. We specifically consider recent research and theory on perseverative reaching by infants as a case study that demonstrates this approach.


Exosomal miR-130a-3p regulates osteogenic differentiation of Human Adipose-Derived stem cells through mediating SIRT7/Wnt/β-catenin axis.
It is of profound significance for clinical bone regeneration to clarify the specific molecular mechanism from which we found that osteogenic differentiation of adipose-derived stem cells (ADSCs) will be probably promoted by exosomes. By means of lentiviral transfection, miR-130a-3p overexpression and knockdown ADSCs were constructed. Alizarin Red S was used to detect the calcium deposits, and qPCR was used to detect osteogenesis-related genes, to verify the effect of miR-130a-3p on the osteogenic differentiation of ADSCs. CCK-8 was used to detect the effect of miR-130a-3p on the proliferation of ADSCs. The target binding between miR-130a-3p and SIRT7 was verified by dual-luciferase reporter gene assay. Furthermore, the role of Wnt signalling pathway in the regulation of ADSCs osteogenesis and differentiation by miR-130a-3p was further verified by detecting osteogenic-related genes and proteins and alkaline phosphatase activity. (a) Overexpression of miR-130a-3p can enhance the osteogenic differentiation of ADSCs while reducing protein and mRNA levels of SIRT7, a target of miR-130a-3p. (b) Our study further found that overexpression of miR-130a-3p leads to down-regulation of SIRT7 expression with up-regulation of Wnt signalling pathway-associated protein. (c) Overexpression of miR-130a-3p inhibited proliferation of ADSCs, while knockdown promoted it. The obtained findings indicate that exosomal miR-130a-3p can promote osteogenic differentiation of ADSCs partly by mediating SIRT7/Wnt/β-catenin axis, which will hence promote the application of exosomal microRNA in the field of bone regeneration.


The treatment of wartime brain wounds: traditional versus minimal debridement.
Since World War II, surgeons in Western armies dealing with brain wounds have generally advocated thorough missile track debridement, and many have urged meticulous dural closure to prevent cerebral spinal fluid (CSF) leakage and subsequent infection. For the last decade some reports have appeared wherein wartime brain wounds have been treated by minimal brain debridement with little or no attention to tight dural closure. This report compares and contrasts postdebridement complications reported with each method. I reviewed the pertinent neurosurgical papers from Vietnam, the Israeli war in Lebanon, and the Iran-Iraq war and compared the results of traditional debridement and water-tight dural closure to those following minimal debridement without close attention to dural closure. Minimal brain debridements without tight dural closure were up to 20 to 30 times more likely to require additional debridement, had a 10-15 times higher incidence of life-threatening CSF leakage, a fivefold increase in postdebridement meningitis, and a 2.5 times greater risk of fatal meningitis. Compared to thorough brain debridement and watertight dural closure, minimal debridements and nonwatertight dural closure give inferior results.


Enhanced butanol production in a microbial electrolysis cell by Clostridium beijerinckii IB4.
Reducing power such as NADH is an essential factor for acetone/butanol/ethanol (ABE) fermentation using Clostridium spp. The objective of this study was to increase available NADH in Clostridium beijerinckii IB4 by a microbial electrolysis cell (MEC) with an electron carrier to enhance butanol production. First of all, a MEC was performed without electron carrier to study the function of cathodic potential applying. Then, various electron carriers were tested, and neutral red (NR)-amended cultures showed an increase of butanol concentration. Optimal NR concentration (0.1 mM) was used to add in a MEC. Electricity stimulated the cell growth obviously and dramatically diminished the fermentation time from 40 to 28 h. NR and electrically reduced NR improved the final butanol concentration and inhibited the acetone generation. In the MEC with NR, the butanol concentration, yield, proportion and productivity were increased by 12.2, 17.4, 7.2 and 60.3 %, respectively. To further understand the mechanisms of NR, cathodic potential applying and electrically reduced NR, NADH and NAD(+) levels, ATP levels and hydrogen production were determined. NR and electrically reduced NR also improved ATP levels and the ratio of NADH/NAD(+), whereas they decreased hydrogen production. Thus, the MEC is an efficient method for enhancing the butanol production.


Combined photolysis and catalytic ozonation of dimethyl phthalate in a high-gravity rotating packed bed.
In this study, a high-gravity rotating packed bed (HGRPB) was used as a catalytic ozonation reactor to decompose dimethyl phthalate (DMP), an endocrine disrupting chemical commonly encountered. The HGRPB is an effective gas-liquid mixing equipment which can enhance the ozone mass transfer coefficient. Platinum-containing catalyst (Pt/-Al2O3) of Dash 220N and ultra violet (UV) lamp were combined in the high-gravity ozonation (HG-OZ) system to enhance the self-decomposition of molecular ozone in liquid to form highly reactive radical species. Different combinations of HG-OZ with Dash 220N and UV for the degradation of DMP were tested. These include HG-OZ, HG catalytic OZ (HG-Pt-OZ), HG photolysis OZ (HG-UV-OZ) and HG-UV-Pt-OZ. The result indicated that all the above four ozonation processes result in significant decomposition of DMP and mineralization of total organic carbon (TOC) at the applied ozone dosage per volume of liquid sample of 1.2gL(-1). The UV and Pt/gamma-Al2O3 combined in HG-OZ can enhance the TOC mineralization efficiency (eta(TOC)) to 56% (via HG-UV-OZ) and 57% (via HG-Pt-OZ), respectively, while only 45% with ozone only. The process of HG-UV-Pt-OZ offers the highest eta(TOC) of about 68%.


FAM87A as a Competing Endogenous RNA of miR-424-5p Suppresses Glioma Progression by Regulating PPM1H.
Far less has been unveiled about the functions of lncRNAs on cancers yet. Here, we reported that lncRNA FAM87A, as a ceRNA of miR-424-5p, played a vital role in glioma development. qRT-PCR result indicated that FAM87A was abnormally downregulated in glioma tissue and cells. Survival analysis suggested that the FAM87A expression was negatively correlated with the survival rate. Effects of FAM87A on human glioma cell lines were also analyzed by MTT, Edu, and transwell assays. FAM87A hastened proliferation and migration of glioma cells. MiR-424-5p, predicted target of FAM87A, was fostered in glioma, which was examined by qRT-PCR. A negative correlation was indicated between FAM87A and miR-424-5p. Results of bioinformatics, dual luciferase, and RIP assays unveiled that FAM87A and miR-424-5p act upon each other. In addition, miR-424-5p targeted 3'-UTR of PPM1H. Also, effects of miR-424-5p/FAM87A on glioma cells were identified via the cell function experiments. FAM87A suppressed PPM1H by binding to miR-424-5p competitively, thereby restraining cell proliferation, migration, and invasion. Collectively, these findings illuminated a new mechanism for glioma progression. Therefore, FAM87A may act as a feasible target for glioma treatment.


Lipid droplets and autophagosomes together with chaperones fine-tune expression of SGK1.
Serum-glucocorticoid-induced kinase-1 (SGK1) regulates ion homeostasis and promotes survival under stress conditions. The expression of SGK1 is under transcriptional and post-translational regulations that are frequently altered in cancer and immune disorders. We report that an N-terminal amphipathic alpha-helix determines SGK1 expression levels through two distinct mechanisms. It tethers SGK1 to intracellular organelles generating a large pool of membrane-bound SGK1, which is differentially stabilized in lipid droplets (LD) in fed conditions or degraded in the endoplasmic reticulum by ER-phagy in starvation. Association of the α-helix to organelles does not depend on dedicated receptors or special phospholipids rather, it is intrinsic to its physicochemical properties and depends on the presence of bulky hydrophobic residues for attachment to LDs. The second mechanism is recruitment of protein-chaperones that recognize the α-helix as an unfolded protein promoting survival of the cytosolic SGK1 fraction. Together, the findings unveil an unexpected link between levels of energy storage and abundance of SGK1 and how changes in calorie intake could be used to modulate SGK1 expression, whereas the inhibition of molecular chaperones could serve as an additional enhancer in the treatment of malignancies and autoimmune disorders with high levels of SGK1 expression.


Comparative gas exchange of four California beach taxa.
Laboratory gas exchange measurements were conducted on four pioneering beach species from southern California. Atriplex leucophylla (Moq.) D. Dietr., a C4 species, had a photosynthetic temperature optimum substantially higher than leaf temperatures normally experienced on the beach during the primary growing season. The C3 species, Cakile maritima Scop., Ambrosia chamissonis Less. and Abronia maritima Nutt. ex Wats., had photosynthetic temperature optima close to their growth temperature and higher photosynthetic rates than the C4 species at normal field growth temperatures. Atriplex leucophylla had higher mesophyll conductances which resulted in higher water use efficiencies at all measurement temperatures. Leaf chlorophyll and protein contents were not correlated with photosynthetic rates. The possible significance of water use efficiency is discussed in relation to the characteristics of the beach habitat.


Vedolizumab therapy for pediatric steroid-refractory gastrointestinal acute graft-versus-host disease.
Vedolizumab, an immunosuppressive drug that acts locally on the gastrointestinal tract, is mainly used for the treatment of inflammatory bowel disease, and has been reported to be effective against gastrointestinal acute graft-versus-host disease (GI-aGVHD) in adults. However, there is insufficient evidence for pediatric GI-aGVHD. We used vedolizumab to treat three cases of GI-aGVHD in patients aged 1.5-4.4 years. It was significantly effective in two patients and did not cause serious side effects in any patient. Vedolizumab might be effective and safe for pediatric GI-aGVHD refractory to other treatments, but this must be confirmed in future studies.


Treatment of experimental Naegleria meningoencephalitis with a combination of amphotericin B and rifamycin.
The treatment of primary amoebic meningoencephalitis was examined using a mouse model. Rifamycin by itself was ineffective. However, a synergistic effect was observed when used in combination with amphotericin B. This finding may prove useful in the treatment of patients with primary amoebic meningoencephalitis, for which satisfactory treatment is currently unavailable.


[Use of the echotomography in the exploration of aneurisms of the abdominal aorta (author's transl)].
Twenty-six cases of abdominal aortic aneurysm were shown by echotomography, at of a series of 80 subjects in whom a pulsatile abdominal mass was perceived clinically or suspected. There seems to exist an excellent correlation between the results echotomography and arteriography concerning either the lesion itself or the ocasional complications such as partial thrombosis, dissection and rupture.


Socioeconomic status and the prevalence of clinical gallbladder disease.
The prevalence of clinical gallbladder disease was determined in a cross-sectional survey of Mexican Americans and non-Hispanic whites. The study population was randomly selected from three urban neighborhoods representing different socioeconomic strata. Gallbladder disease was defined as a history of cholecystectomy, or of stones on cholecystography. Mexican American women had an age-standardized prevalence of 16.9%, vs 8.7% for non-Hispanic whites (p less than 0.0001). Prevalences in men were 4.2 and 3.4%, respectively. The ethnic differences in women persisted after stratification by age, parity, and body mass index. Gallbladder disease prevalence was inversely related to four measures of socioeconomic status. After controlling for age, obesity, parity, and ethnicity, the prevalence in women was inversely related to levels of education, income, occupational status, and neighborhood. These socioeconomic differences, if not the result of detection bias, suggest that environmental factors may play a role in gallstone pathogenesis. Identification of such factors may lead to the development of preventive strategies.


One-pot preparation of layered double oxides-engineered biochar for the sustained removal of tetracycline in water.
Tetracycline (TC) and sugarcane bagasse had both exerted enormous strain on environmental security. In this work, new composite adsorbent designed by impregnating bio-waste bagasse with magnesium-aluminum layered double oxides (BC-MA) was innovatively brought forward for TC removal. Benefiting from the abundant adsorption sites supplied by developed pores structure (0.308 cm3·g-1), enlarged surface area (256.8 m2·g-1) and reinforced functional groups, the maximum adsorption amount of BC-MA for TC reached 250.6 mg g-1. Moreover, BC-MA displayed desirable adsorption capacity in diverse water environments coupled with excellent sustainable regeneration ability. The absorption process of TC by BC-MA was spontaneous and endothermic, and the pivotal rate-limiting stage pertained to intraparticle diffusion. The mechanisms proposed here mainly concerned π-π interactions, pore filling, complexation and hydrogen bonding. These findings suggested that the synthesis of modified biochar from bagasse would offer new opportunities for simultaneous waste resource reuse and water pollution control.


Calcium ions inhibit reduction of heme a in bovine cytochrome c oxidase.
The effect of Ca(2+) on the rate of heme a reduction by dithionite and hexaammineruthenium (RuAm) was studied in the cyanide-complexed bovine cytochrome oxidase (CcO). The rate of heme a reduction is proportional to RuAm concentration below 300 μM with kv of 0.53×10(6) M(-1) s(-1). Ca(2+) inhibits the rate of heme a reduction by dithionite by ∼25%. As the reaction speeds up with increased concentrations of RuAm, the inhibition by Ca(2+) disappears. The inhibition of heme a reduction may contribute to recently described partial inhibition of CcO by Ca(2+) in the enzymatic assays. The inhibitory effect of Ca(2+) on heme a reduction indicates that ET through heme a may be coupled to proton movement in the exit part of the proton channel H.


An analysis of predictive markers for intracranial haemorrhage in warfarinised head injury patients.
Minor head injury in older patients on warfarin may present in a variety of ways that often fall outside the remit of conventional guidelines. The aim of this study was to determine the relative risks for intracranial haemorrhage (ICH) in patients with subtherapeutic, therapeutic and supratherapeutic INR levels, in addition to the relative risks for the common symptoms at presentation. The notes were retrospectively reviewed of all patients who had a CT scan requested by the emergency department over a 2-year period (January 2008 to December 2009) and from these warfarinised head injuries were identified. 82 warfarinised head injury patients were identified from 3338 requested CT scans. 12 of these patients (15%) had evidence of ICH on the CT. 72 patients had their INR checked (88%) and the RR of ICH for the INR subgroups were calculated: INR <2 (RR 1.89; 95% CI 0.65 to 5.55); INR 2-3 (RR 0.84; 95% CI 0.27 to 2.64); and INR >3 (RR 0.53; 95% CI 0.13 to 2.29). The greatest proportion of those with ICH (42%) had a subtherapeutic INR. 2 out of the 12 patients (17%) were found to have intracranial bleeding despite not meeting the criteria for a CT scan according to the NICE guidelines. The results of the INR subgroup analysis suggest that a subtherapeutic INR may not be protective against ICH in patients with minor head injury.


Meeting the Sexual Health Needs of Bisexual Men in the Age of Biomedical HIV Prevention: Gaps and Priorities.
The field of HIV/STI prevention has primarily focused on gay men (or "men who have sex with men" [MSM] as a broad category) with limited attention to bisexual men in particular. Although bisexual men are also at increased risk for HIV and other STI, they are less likely to utilize HIV/STI prevention services than gay men, and very few interventions have been developed to address their unique needs. Further, while biomedical advances are changing the field of HIV prevention, bisexual men are also less likely to use biomedical HIV prevention strategies (e.g., pre-exposure prophylaxis [PrEP]) than gay men. In an effort to advance research on bisexual men and their sexual health needs, the goals of this commentary are: (1) to review the empirical literature on the prevalence of HIV/STI among bisexual men, the few existing HIV/STI prevention interventions developed for bisexual men, and the use of biomedical HIV prevention among bisexual men; (2) to describe the ways in which the field of HIV/STI prevention has largely overlooked bisexual men as a population in need of targeted services; and (3) to discuss how researchers can better address the sexual health needs of bisexual men in the age of biomedical HIV prevention.


Identifying predictive biomarkers of CIMAvaxEGF success in non-small cell lung cancer patients.
Immunosenescence biomarkers and peripheral blood parameters are evaluated separately as possible predictive markers of immunotherapy. Here, we illustrate the use of a causal inference model to identify predictive biomarkers of CIMAvaxEGF success in the treatment of Non-Small Cell Lung Cancer Patients. Data from a controlled clinical trial evaluating the effect of CIMAvax-EGF were analyzed retrospectively, following a causal inference approach. Pre-treatment potential predictive biomarkers included basal serum EGF concentration, peripheral blood parameters and immunosenescence biomarkers. The proportion of CD8 + CD28- T cells, CD4+ and CD8+ T cells, CD4/CD8 ratio and CD19+ B cells. The 33 patients with complete information were included. The predictive causal information (PCI) was calculated for all possible models. The model with a minimum number of predictors, but with high prediction accuracy (PCI > 0.7) was selected. Good, rare and poor responder patients were identified using the predictive probability of treatment success. The mean of PCI increased from 0.486, when only one predictor is considered, to 0.98 using the multivariate approach with all predictors. The model considering the proportion of CD4+ T cell, basal Epidermal Growth Factor (EGF) concentration, neutrophil to lymphocyte ratio, Monocytes, and Neutrophils as predictors were selected (PCI > 0.74). Patients predicted as good responders according to the pre-treatment biomarkers values treated with CIMAvax-EGF had a significant higher observed survival compared with the control group (p = 0.03). No difference was observed for bad responders. Peripheral blood parameters and immunosenescence biomarkers together with basal EGF concentration in serum resulted in good predictors of the CIMAvax-EGF success in advanced NSCLC. Future research should explore molecular and genetic profile as biomarkers for CIMAvax-EGF and it combination with immune-checkpoint inhibitors. The study illustrates the application of a new methodology, based on causal inference, to evaluate multivariate pre-treatment predictors. The multivariate approach allows realistic predictions of the clinical benefit of patients and should be introduced in daily clinical practice.


Black grain mycetoma. Atomic absorption and spark source mass spectrophotometry of the tissue grain in Madurella mycetomi infection.
The tissue grain of Madurella mycetomi infection shows a spread of mineral constituents which is somewhat higher than the known values for the dermis, but differs little in relative concentrations. The unique physical resistance of the grain cannot be related to departures in concentration of calcium or of trace elements. Our earlier hypothesis of a tanned protein structure for the grain therefore still holds (Findlay & Vismer, 1974).


Women's and clinician's acceptability of participation in a hypothetical obstetric randomized controlled trial: a qualitative survey.
Involving patients and consumers in research design helps ensure relevance for those affected by the problem being investigated and can optimize recruitment to clinical trials. This is particularly important when conducting research involving pregnant women. We investigated women's motivations to participate in a hypothetical randomized control trial (RCT) of a third-trimester screening test for intrapartum fetal compromise (IFC) and adverse perinatal outcomes. Women attending for routine antenatal care at a tertiary center were invited to complete a short, anonymized patient acceptability survey. The survey was developed with the assistance of the Perinatal Society of Australia and New Zealand's Consumer Advisory Panel and consisted of Likert scales and open-ended questions. It was designed to ascertain women's responses to research issues, particularly the acceptability of being randomized to a non-revealed arm of a screening test RCT. 100 pregnant women took part; 40% indicated that they would agree/strongly agree to participate in a hypothetical RCT regardless of whether they were given the result of a screening test and 31% were unsure. Randomization to either an intervention or control group was acceptable to 47%, 30% were unsure and 23% were not willing to be randomized. Reasons to participate included the desire to contribute to research and to improve pregnancy care. Participation in an RCT of a screening test for IFC involving non-disclosure of the test result was acceptable to a large minority of pregnant women. This finding supports the feasibility of conducting a large-scale study of this design.


Trends in the incidence of syphilis in the middle-aged and older adults in Japan: A nationwide observational study, 2009-2019.
Sexually transmitted infections remain a neglected area of research in geriatrics. However, in the global aging societies, sexual health among the middle-aged and older adults is an emerging public concern. High-income countries are facing a resurgence of syphilis cases among young generations, but little is known about its prevalence in older populations. We aimed to investigate the national trend of syphilis cases in Japan. This nationwide observational study used the publicly-available database (2009-2019) to calculate crude and age-adjusted incidence rates of syphilis per 100 000 population by age, sex and clinical stage. We collected data from patients aged ≥50 years and performed joinpoint regression analysis to estimate long-term trends and average annual percentage changes (AAPCs). The total number of patients with syphilis increased about 8-fold from 165 in 2009 to 1280 in 2019. AAPCs of crude incidence rates significantly increased in every age category; 33.2% in 50-59 years, 23.8% in 60-69 years and 20.9% in ≥70 years. Age-adjusted incidence rates have surged at AAPCs of 28.7% in men and 23.1% in women, reaching 4.09 in men and 0.71 in women in 2019. By clinical stage, marked increases were observed in primary (AAPCs, 42.3% in men and 41.6% in women) and secondary syphilis (AAPCs, 24.9% in men and 24.2% in women). An up-toward trend of syphilis among people aged ≥50 years was observed. The importance of sexual health among older people should be highlighted in this aging Japanese society. Geriatr Gerontol Int 2022; 22: 1019-1024.


Early results from a novel quality outcomes program: the American Society Of Breast Surgeons' Mastery of Breast Surgery.
In 2008, the American Society for Breast Surgeons launched its Mastery in Breast Surgery Pilot Program to demonstrate feasibility of a Web-based tool for breast surgeons to document and monitor quality outcomes. Participating surgeons report performance of three quality measures for breast procedures: Was a needle biopsy performed to evaluate the breast lesion before the procedure? Was the surgical specimen oriented? For nonpalpable lesions localized with image guidance, was there intraoperative confirmation of removal? Data are collected through the American Society for Breast Surgeons' Web-based software using a secure server and encrypted identification numbers. Surgeon demographic/practice characteristic data were collected, and logistic regression models were used to identify factors that affected quality measures. From October 2008 to December 2009, a total of 696 surgeons entered data for 28,798 breast procedures. Participants were diverse in years in practice, geographic location, practice setting and type, and proportion of practice made up of breast procedures. Delivery of "optimal care" (defined as delivery of all quality measures for which there was no valid clinical reason for nonperformance) was high for all surgeon demographic/practice characteristics, ranging from 81% to 94%. Statistically significant differences in delivery of quality measures were observed within all physician demographic/practice characteristic variables, but many absolute differences were small. The high level of participation and volume of breast procedures for which quality measure data was entered demonstrate this is a feasible means of collecting quality performance data. Future development will include identifying/developing additional quality measures and establishing evidence-based benchmarks for care on the basis of data collected.


Sequencing genomes to aid conservation.
Georgina Mills explains how a research institute is celebrating its 25th birthday by sequencing 25 genomes.


Anesthetic management of an infant with Joubert syndrome for cardiac surgery.
The anesthetic implications of Joubert syndrome in an infant who required cardiac surgery using cardiopulmonary bypass (CPB) is presented. Children with Joubert syndrome present with central apnea due to malformations in the midbrain and cerebellum. These patients have a marked sensitivity to opioids. The use of dexmedetomidine along with remifentanil was effective in this case.


AD-NET: Age-adjust neural network for improved MCI to AD conversion prediction.
The prediction of Mild Cognitive Impairment (MCI) patients who are at higher risk converting to Alzheimer's Disease (AD) is critical for effective intervention and patient selection in clinical trials. Different biomarkers including neuroimaging have been developed to serve the purpose. With extensive methodology development efforts on neuroimaging, an emerging field is deep learning research. One great challenge facing deep learning is the limited medical imaging data available. To address the issue, researchers explore the use of transfer learning to extend the applicability of deep models on neuroimaging research for AD diagnosis and prognosis. Existing transfer learning models mostly focus on transferring the features from the pre-training into the fine-tuning stage. Recognizing the advantages of the knowledge gained during the pre-training, we propose an AD-NET (Age-adjust neural network) with the pre-training model serving two purposes: extracting and transferring features; and obtaining and transferring knowledge. Specifically, the knowledge being transferred in this research is an age-related surrogate biomarker. To evaluate the effectiveness of the proposed approach, AD-NET is compared with 8 classification models from literature using the same public neuroimaging dataset. Experimental results show that the proposed AD-NET outperforms the competing models in predicting the MCI patients at risk for conversion to the AD stage.


Radiotherapy of bone metastases.
We present the update of the recommendations of the French society of oncological radiotherapy on bone metastases. This is a common treatment in the management of patients with cancer. It is a relatively simple treatment with proven efficacy in reducing pain or managing spinal cord compression. More complex treatments by stereotaxis can be proposed for oligometastatic patients or in case of reirradiation. In this context, increased vigilance should be given to the risks to the spinal cord.


Uterine microvascular sensitivity to nanomaterial inhalation: An in vivo assessment.
With the tremendous number and diverse applications of engineered nanomaterials incorporated in daily human activity, exposure can no longer be solely confined to occupational exposures of healthy male models. Cardiovascular and endothelial cell dysfunction have been established using in vitro and in situ preparations, but the translation to intact in vivo models is limited. Intravital microscopy has been used extensively to understand microvascular physiology while maintaining in vivo neurogenic, humoral, and myogenic control. However, a tissue specific model to assess the influences of nanomaterial exposure on female reproductive health has not been fully elucidated. Female Sprague Dawley (SD) rats were exposed to nano-TiO2 aerosols (171 ± 6 nm, 10.1 ± 0.39 mg/m(3), 5h) 24-hours prior to experimentation, leading to a calculated deposition of 42.0 ± 1.65 μg. After verifying estrus status, vital signs were monitored and the right horn of the uterus was exteriorized, gently secured over an optical pedestal, and enclosed in a warmed tissue bath using intravital microscopy techniques. After equilibration, significantly higher leukocyte-endothelium interactions were recorded in the exposed group. Arteriolar responsiveness was assessed using ionophoretically applied agents: muscarinic agonist acetylcholine (0.025 M; ACh; 20, 40, 100, and 200 nA), and nitric oxide donor sodium nitroprusside (0.05 M; SNP; 20, 40, and 100 nA), or adrenergic agonist phenylephrine (0.05 M; PE; 20, 40, and 100 nA) using glass micropipettes. Passive diameter was established by tissue superfusion with 10(-4)M adenosine. Similar to male counterparts, female SD rats present systemic microvascular dysfunction; however the ramifications associated with female health and reproduction have yet to be elucidated.


Perceptions of Rural SNAP-Authorized Food Store Owners and Managers About Healthy Product Availability.
Supplemental Nutrition Assistance Program (SNAP)-authorized retailers' healthy perceptions and store availability of healthy products were explored to plan a healthy food retail program. Cognitive anthropology (free list) and quantitative (food environment measure) methods were used to assess retailers' healthy product perceptions and the availability of store products aligned with dietary guidance. Cultural domain analysis techniques and descriptive and inferential statistics were used to interpret data. SNAP-authorized retailers (n = 29) of rural grocery (17%), dollar (14%), convenience (66%), and specialty (3%) stores participated. There was low salience for what constituted healthy and misalignments with dietary guidance and inventory. Dried beans, nuts, and seeds were widely available products across all stores and were listed less frequently by retailers. Engagement with SNAP-authorized retailers to develop retailer-focused nutrition education and/or training protocols is warranted to improve the capacity for retailers to market store products aligned with dietary guidance.


Discovery of the Potent and Selective M1 PAM-Agonist N-[(3R,4S)-3-Hydroxytetrahydro-2H-pyran-4-yl]-5-methyl-4-[4-(1,3-thiazol-4-yl)benzyl]pyridine-2-carboxamide (PF-06767832): Evaluation of Efficacy and Cholinergic Side Effects.
It is hypothesized that selective muscarinic M1 subtype activation could be a strategy to provide cognitive benefits to schizophrenia and Alzheimer's disease patients while minimizing the cholinergic side effects observed with nonselective muscarinic orthosteric agonists. Selective activation of M1 with a positive allosteric modulator (PAM) has emerged as a new approach to achieve selective M1 activation. This manuscript describes the development of a series of M1-selective pyridone and pyridine amides and their key pharmacophores. Compound 38 (PF-06767832) is a high quality M1 selective PAM that has well-aligned physicochemical properties, good brain penetration and pharmacokinetic properties. Extensive safety profiling suggested that despite being devoid of mAChR M2/M3 subtype activity, compound 38 still carries gastrointestinal and cardiovascular side effects. These data provide strong evidence that M1 activation contributes to the cholinergic liabilities that were previously attributed to activation of the M2 and M3 receptors.


Synthesis, crystal structure, Hirshfeld surface analysis, MEP study and mol-ecular docking of N-{3-[(4-meth-oxy-phen-yl)carbamo-yl]phen-yl}-3-nitro-benzamide as a promising inhibitor of hfXa.
The title compound, C21H17N3O5, consists of three rings, A, B and C, linked by amide bonds with the benzene rings A and C being inclined to the mean plane of the central benzene ring B by 2.99 (18) and 4.57 (18)°, respectively. In the crystal, mol-ecules are linked via N-H⋯O and C-H⋯O hydrogen bonds, forming fused R 2 2(18), R 3 4(30), R 4 4(38) rings running along [0] and R 3 3(37) and R 3 3(15) rings along [001]. Hirshfeld analysis was undertaken to study the inter-molecular contacts in the crystal, showing that the most significant contacts are H⋯O/O⋯H (30.5%), H⋯C/C⋯H (28.2%) and H⋯H (29.0%). Two zones with positive (50.98 and 42.92 kcal mol-1) potentials and two zones with negative (-42.22 and -34.63 kcal mol-1) potentials promote the N-H⋯O inter-actions in the crystal. An evaluation of the mol-ecular coupling of the title compound and the protein with enzymatic properties known as human coagulation factor Xa (hfXa) showed the potential for coupling in three arrangements with a similar minimum binding energy, which differs by approximately 3 kcal mol-1 from the value for the mol-ecule Apixaban, which was used as a positive control inhibitor. This suggests the title compound exhibits inhibitory activity.


Structure and luminescence properties of Dy3+ doped quaternary tungstate Li3Ba2Gd3(WO4)8 for application in wLEDs.
Quaternary tungstates with the composition Li3Ba2Gd3(WO4)8 doped with different concentrations of Dy3+ (from 0.5 to 10 at%) were prepared by the solid-state reaction method at 900 °C. Their structural, spectroscopic and optical properties were studied systematically in this work. X-ray diffraction analysis confirmed the crystallization of Li3Ba2Gd3(WO4)8 to have a monoclinic structure (sp. gr. C2/c); the lattice constants for 1 at% doping concentration of Dy3+ are a = 5.2126(2) Å, b = 12.7382(1) Å, c = 19.1884(3) Å, Vcalc = 1273,40(4) Å3 and β = a × c = 91.890(9)°. The first principles calculations for the undoped crystal revealed a direct bandgap of 2.45 eV, which is very close to the experimental one. The identified broad, and strong excitation peak at 450 nm indicates that Li3Ba2Gd3(WO4)8:Dy3+ phosphors are suitable to be pumped by a blue laser diode (LD). Under excitation at 445 nm, the phosphor showed a stronger luminescence peak at 575 nm which corresponds to the Dy3+:4F9/2 → 6H13/2 transition, and three weaker emissions peaks at 477, 661, and 750 nm. Meanwhile, the effect of different Dy3+ contents on the luminescence properties was investigated. The optimum concentration to minimize the quenching effect was 4 at% and the critical distance is 31.209 Å. The phosphor emitted strong greenish-yellow light situated at (0.425, 0.472) in CIE coordinates with a color temperature of 3652 K. All the measured luminescence lifetime curves exhibited a single-exponential nature. Excellent thermal stability was found for this tungstate phosphor (the activation energy is 0.352 ± 0.01 eV). The measured absolute photoluminescence quantum yield was around 10.5%. The results presented in this work show that Li3Ba2Gd3(WO4)8:Dy3+ phosphors with strong yellow emission are promising candidates for white-light emitting LED (wLED) applications.


Forensically relevant challenging behaviors and the genetics domain.
Impulsive and aggressive behaviors along with intellectual disabilities often manifest in the context of genetic disorders and are a persisting challenge to professionals in the forensic psychiatric and psychological setting. The following chapter comprises an overview of relevant factors in the gene-context-behavior interaction such as monoamine oxidase A activity and specific epileptic phenomena. It presents several examples of monogenetic disorders with behaviors from the aggression spectrum and summarizes emerging strategies for treatment and clinical management thereof. The final part focuses on challenges and future developments in this field with relevance for the judicial and forensic systems. It is concluded that the relationship between a genetic syndrome and forensically relevant and/or violent behaviors should typically be addressed within a multidisciplinary framework that also includes the application of modern genetic techniques.


Physical activity and the incidence of obesity in young African-American women.
Obesity occurs more commonly among African-American women than among other racial/ethnic groups, and most weight gain occurs before middle age. The study prospectively investigated the relationship of vigorous exercise and brisk walking to the incidence of obesity (BMI ≥ 30) among African-American women aged <40 years. During 1995-2009 in the Black Women's Health Study, the current authors followed 20,259 African-American women who were aged <40 years and not obese at baseline. BMI, exercise, and walking were assessed at baseline and on biennial follow-up questionnaires. Data for BMI were collected through 2009. Data for exercise and walking were collected through 2007. Validation and reproducibility data indicated that reporting was more accurate for vigorous exercise than for brisk walking. Cox proportional hazards models estimated incidence rate ratios (IRRs) and 95% CIs of incident obesity for hours/week of vigorous exercise and walking relative to "little or no exercise" (<1 hour/week of vigorous exercise and <1 hour/week of brisk walking). The analyses were conducted in 2012. The incidence of obesity decreased with increasing vigorous exercise; the IRR was 0.77 (95% CI=0.69, 0.85) for ≥ 7 hours/week relative to little or no exercise; the IRRs were reduced both among women with a healthy weight (BMI <25) at baseline and among women who were overweight (BMI 25-<30) at baseline. The IRRs for brisk walking for exercise and walking for transport were <1.0 for most levels of walking, but without clear trends of decreasing risk with increasing time spent walking. The results suggest that vigorous exercise may reduce the incidence of obesity among young African-American women. Results for brisk walking were inconclusive.


Issues and challenges for development of a sustainable service model for people with spinal cord injury living in rural regions.
To develop and implement a service model for people with spinal cord injury (SCI) living in rural regions. Service development, pilot evaluation study. Regional and remote areas of the state of New South Wales, Australia. Persons with SCI, caregivers, and health professionals. Phase 1 included initial needs analysis, followed by education and resource development tailored to needs of rural health professionals, caregivers, and persons with SCI. Phase 2 included coordination, professional support, and network development by part-time rural key worker and metropolitan-based project officer, documenting health- and service-related issues. Self-perception of confidence as a result of education as well as reported issues, adverse health events, and barriers to service provision. Clinician confidence in managing people with SCI improved after education. Various health-related, environmental, and psychosocial issues were reported. Limited availability of resources and health infrastructure, particularly in more isolated or smaller towns, challenged service provision. Rural key workers played a central role in supporting local clinicians and service providers, improving communication and service coordination between rural health professionals and metropolitan SCI services. Education and support for rural workforce that may be limited in numbers and capacity, and a model facilitating communication and coordination between services, are essential for improving health outcomes of rural people with SCI.


Identification of trans-4-[1-[[7-fluoro-2-(1-methyl-3-indolyl)-6-benzoxazolyl]acetyl]-(4S)-fluoro-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylic acid as a potent, orally active VLA-4 antagonist.
For the purpose of obtaining orally potent VLA-4 inhibitors, we have carried out structural modification of the (N'-phenylureido)phenyl group in compound 1, where the group was found to be attributed to poor pharmacokinetic profile in our previous research. Through modification, we have identified several compounds with both potent in vitro activity and improved oral exposure. In particular, compound 7e with 7-fluoro-2-(1-methyl-1H-indol-3-yl)-1,3-benzoxazolyl group as a novel replacement of the (N'-phenylureido)phenyl group significantly inhibited eosinophil infiltration into bronchoalveolar lavage fluid at 15mg/kg in an Ascaris-antigen-induced murine bronchial inflammatory model, and its efficacy was comparable to that of the anti-mouse α(4) antibody (R1-2).


Bannwarth's syndrome and the enlarged neurological spectrum of arthropod-borne borreliosis.
We evaluated the clinical data of 80 patients with neurological disorders due to European arthropod-borne Borrelia burgdorferi infections proven by specific antibody titers. Painful meningoradiculitis of Bannwarth was the predominant neurological manifestation in adults, whereas meningitis with headache and slight stiff neck was the most frequent neurological syndrome in children. Central nervous system involvement occurred only in 13% of the patients; one of these patients had chronic encephalomyelitis for several years. Particularly in those inflammatory neurological diseases without a known history of arthropod bite or erythema migrans serological diagnosis may clarify the clinical condition.


Optimizing the Transition and Transfer of Care in Pediatric Inflammatory Bowel Disease.
Health care transition from pediatric to adult care has been identified as a priority in the field of medicine, especially for those with chronic illnesses such as inflammatory bowel disease (IBD). Although there is no universally accepted model of preparing the pediatric patient for transfer to adult care, transition care is best accomplished in a structured and consistent manner. The authors highlight concepts for optimizing the transition of care for patients with IBD, which include setting expectations throughout adolescence with the gradual nurturing of self-management skills, preparing and assessing of readiness for transfer, and enacting a successful transfer to adult care.


Testing the use of ITS rDNA and protein-coding genes in the generic and species delimitation of the lichen genus Usnea (Parmeliaceae, Ascomycota).
In lichen-forming fungi, traditional taxonomical concepts are frequently in conflict with molecular data, and identifying appropriate taxonomic characters to describe phylogenetic clades remains challenging in many groups. The selection of suitable markers for the reconstruction of solid phylogenetic hypotheses is therefore fundamental. The lichen genus Usnea is highly diverse, with more than 350 estimated species, distributed in polar, temperate and tropical regions. The phylogeny and classification of Usnea have been a matter of debate, given the lack of phenotypic characters to describe phylogenetic clades and the low degree of resolution of phylogenetic trees. In this study, we investigated the phylogenetic relationships of 52 Usnea species from across the genus, based on ITS rDNA, nuLSU, and two protein-coding genes RPB1 and MCM7. ITS comprised several highly variable regions, containing substantial genetic signal, but also susceptible to causing bias in the generation of the alignment. We compared several methods of alignment of ITS and found that a simultaneous optimization of alignment and phylogeny (using BAli-phy) improved significantly both the topology and the resolution of the phylogenetic tree. However the resolution was even better when using protein-coding genes, especially RPB1 although it is less variable. The phylogeny based on the concatenated dataset revealed that the genus Usnea is subdivided into four highly-supported clades, corresponding to the traditionally circumscribed subgenera Eumitria, Dolichousnea, Neuropogon and Usnea. However, characters that have been used to describe these clades are often homoplasious within the phylogeny and their parallel evolution is suggested. On the other hand, most of the species were reconstructed as monophyletic, indicating that combinations of phenotypic characters are suitable discriminators for delimitating species, but are inadequate to describe generic subdivisions.


Update on active surveillance for clinical T1 renal tumors.
The purpose is to discuss current data on the utilization and outcomes of active surveillance for T1a renal masses. Specifically, to address which patients are optimal for active surveillance and how their outcomes differ from those undergoing immediate treatment. Although nephron sparing surgery is the standard of care for small renal masses (SRMs), active surveillance is becoming a more popular intervention given the results of prospective studies revealing active surveillance to be safe and have excellent cancer-specific survival with intermediate follow-up. Older and sicker patients have competing risk of death from other causes when diagnosed with a SRM. Active surveillance is becoming a more popular treatment modality for SRMs given the increasing number of incidental diagnoses and better understanding of their often indolent course. Active surveillance with delayed intervention is a well-tolerated treatment modality and appears to have the most benefit for those patients that are older with more comorbidities.


Astrocytic C-X-C motif chemokine ligand-1 mediates β-amyloid-induced synaptotoxicity.
Pathological interactions between β-amyloid (Aβ) and tau drive synapse loss and cognitive decline in Alzheimer's disease (AD). Reactive astrocytes, displaying altered functions, are also a prominent feature of AD brain. This large and heterogeneous population of cells are increasingly recognised as contributing to early phases of disease. However, the contribution of astrocytes to Aβ-induced synaptotoxicity in AD is not well understood. We stimulated mouse and human astrocytes with conditioned medium containing concentrations and species of human Aβ that mimic those in human AD brain. Medium from stimulated astrocytes was collected and immunodepleted of Aβ before being added to naïve rodent or human neuron cultures. A cytokine, identified in unbiased screens of stimulated astrocyte media and in postmortem human AD brain lysates was also applied to neurons, including those pre-treated with a chemokine receptor antagonist. Tau mislocalisation, synaptic markers and dendritic spine numbers were measured in cultured neurons and organotypic brain slice cultures. We found that conditioned medium from stimulated astrocytes induces exaggerated synaptotoxicity that is recapitulated following spiking of neuron culture medium with recombinant C-X-C motif chemokine ligand-1 (CXCL1), a chemokine upregulated in AD brain. Antagonism of neuronal C-X-C motif chemokine receptor 2 (CXCR2) prevented synaptotoxicity in response to CXCL1 and Aβ-stimulated astrocyte secretions. Our data indicate that astrocytes exacerbate the synaptotoxic effects of Aβ via interactions of astrocytic CXCL1 and neuronal CXCR2 receptors, highlighting this chemokine-receptor pair as a novel target for therapeutic intervention in AD.


Demonstration by class I gene transfer that reduced susceptibility of human cells to natural killer cell-mediated lysis is inversely correlated with HLA class I antigen expression.
HLA antigen-loss mutants and class I gene transferents were used to analyze the influence of class I expression on natural killer (NK) cell-mediated lysis. Only HLA antigen-loss mutants that had lost expression of either HLA-A and HLA-B antigens (mutant .184) or of HLA-A, B and C antigens (mutant .221) were distinctly susceptible to NK-mediated lysis. Mutants with reduced expression of class II antigens but unaltered expression of class I antigens remained resistant to NK lysis. A direct demonstration of the effect of class I antigen expression on human cells was made by analyzing a variety of gene transferents of the HLA-A, B, C null mutant .221 expressing only one transferred HLA-A, B or C gene. These results specifically show that expression of class I antigens, with a possible preferential effect of HLA-B expression, reduces the susceptibility of mutant .221 to NK-mediated lysis.


Case-ascertained study of household transmission of seasonal influenza - South Africa, 2013.
The household is important in influenza transmission due to intensity of contact. Previous studies reported secondary attack rates (SAR) of 4-10% for laboratory-confirmed influenza in the household. Few have been conducted in middle-income countries. We performed a case-ascertained household transmission study during May-October 2013. Index cases were patients with influenza-like-illness (cough and self-reported or measured fever (≥38 °C)) with onset in the last 3 days and no sick household contacts, at clinics in South Africa. Household contacts of index cases with laboratory-confirmed influenza were followed for 12 days. Thirty index cases in 30 households and 107/110 (97%) eligible household contacts were enrolled. Assuming those not enrolled were influenza negative, 21/110 household contacts had laboratory-confirmed influenza (SAR 19%); the mean serial interval was 2.1 days (SD = 0.35, range 2-3 days). Most (62/82; 76%) household contacts who completed the risk factor questionnaire never avoided contact and 43/82 (52%) continued to share a bed with the index case after illness onset. SAR for laboratory-confirmed influenza in South Africa was higher than previously reported SARs. Household contacts did not report changing behaviors to prevent transmission. These results can be used to understand and predict influenza transmission in similar middle-income settings.


Colistin-induced pulmonary toxicity involves the activation of NOX4/TGF-β/mtROS pathway and the inhibition of Akt/mTOR pathway.
Colistin therapy can cause pulmonary toxicity, however, our understanding of the underlying molecular mechanism remains incomplete. This study aimed to investigate the molecular mechanism of colistin-induced pulmonary toxicity in vitro and in vivo. Our results showed that intraperitoneal colistin treatment significantly increased the expression of TGF-β and NOX4 protein and mRNA, then triggers oxidative stress, mitochondrial dysfunction, and apoptosis in the lung tissue of mice and A549 cells. Moreover, colistin treatment significantly increased levels of mitochondrial ROS (mtROS) and autophagy flux in A549 cells. Inhibition of NOX4 protected A549 cells against colistin-induced mtROS and apoptosis. Colistin treatment also down-regulated the expression of p-Akt and p-mTOR proteins (all P < 0.05 or 0.01) in lung tissues of mice or A549 cells. Inhibition of autophagy or Akt pathways by chloroquine (CQ), 3-Methyladenine (3-MA) or LY294002 promoted colistin-induced mitochondrial damage, and caspase-dependent cellular apoptosis. Whereas, activation of autophagy by rapamycin pretreatment of A549 cells partly abolished colistin-induced cytotoxicity, mitochondrial dysfunction, and apoptosis. This is first study to show that colistin-induced pulmonary toxicity involves the activation of TGF-β/NOX4/mtROS pathway and the inhibition of Akt/mTOR pathway in lung tissues of mice and highlights the key protective role of autophagy activation.


Manual Thrombus Aspiration and the Improved Survival of Patients With Unstable Angina Pectoris Treated With Percutaneous Coronary Intervention (30 Months Follow-Up).
The clinical effect of intracoronary thrombus aspiration during percutaneous coronary intervention in patients with unstable angina pectoris is unknown. In this study, we aimed to assess how thrombus aspiration during percutaneous coronary intervention affects in-hospital and 30-month mortality and complications in patients with unstable angina pectoris.We undertook an observational cohort study of 645 consecutive unstable angina pectoris patients who had performed percutaneous coronary intervention from February 2011 to March 2013. Before intervention, 159 patients who had culprit lesion with thrombus were randomly assigned to group 1 (thrombus aspiration group) and group 2 (stand-alone percutaneous coronary intervention group). All patients were followed-up 30 months until August 2015.Thrombus aspiration was performed in 64 patients (46%) whose cardiac markers (ie, creatinine kinase [CK-MB] mass and troponin T) were significantly lower after percutaneous coronary intervention than in those of group 2 (CK-MB mass: 3.80 ± 1.11 vs 4.23 ± 0.89, P = 0.012; troponin T: 0.012 ± 0.014 vs 0.018 ± 0.008, P = 0.002). Left ventricular ejection fraction at 6, 12, and 24 months postintervention was significantly higher in the group 1. During a mean follow-up period of 28.87 ± 6.28 months, mortality rates were 6.3% in the group 1 versus 12.9% in the group 2. Thrombus aspiration was also associated with significantly less long-term mortality in unstable angina pectoris patients (adjusted HR: 4.61, 95% CI: 1.16-18.21, P = 0.029).Thrombus aspiration in the context of unstable angina pectoris is associated with a limited elevation in cardiac enzymes during intervention that minimises microembolization and significantly improves both of epicardial flow and myocardial perfusion, as shown by angiographic TIMI flow grade and frame count. Thrombus aspiration during percutaneous coronary intervention in unstable angina pectoris patients has better survival over a 30-month follow-up period.


Ultra-thin porous glass membranes--an innovative material for the immobilization of active species for optical chemosensors.
In addition to polymers, porous glasses can be used for the immobilization of indicators, chromoionophores or enzymes. Advantages of these materials include, among others, the photochemical and thermal stability. Porous glass membranes (CPG) based on phase-separated alkali borosilicate glasses with thicknesses of 250-300 μm and dimensions of approximately 9-13 mm² were used in this work. The average pore diameter was found to be between 12 and 112 nm. Initially, the membrane permeability for water was determined. Furthermore, the absorption spectra for the water-soaked membranes were recorded optically. CPG membranes which are pH-sensitive were prepared based on the covalent immobilization of thymol blue and a derivative of styryl acridine. In each case, the absorption spectra of the immobilized indicators are shown. The t90-times vary between 4 and 20 min and were determined for the thermodynamic equilibrium. The influence of the ionic strength on the characteristic curve is discussed and detailed results are given. After the storage time of about 900 days a pH-sensitivity for a CPG membrane styryl acridine derivative sample was still detectable.


Morphological and pomological diversity of wild Prunus microcarpa Boiss. germplasm.
Prunus microcarpa Boiss. is usually found in dry calcareous and rocky mountain slopes and is well adapted to severe winter and dry-hot summer conditions. Morphological and pomological diversity among 81 accessions of P. microcarpa species selected from natural habitats was assessed. The accessions investigated were significantly different from each other in terms of the traits recorded. Tree growth habit was highly variable, including weeping, spreading, open, semi-erect, and erect. Most of the accessions had very small leaves, a probable adaptation to the xerophytic conditions. Ripening date ranged from mid-June to early August. Fruit weight as the first character considering in domestication process ranged from 0.21 to 0.44 g. Principal component analysis (PCA) could describe the evaluated traits as the 11 main components that were able to justify 76.29% of total variance. Also, the accessions were clustered into two major clusters by the Ward dendrogram. Significant diversity was revealed, regarding the morphological traits in the evaluated P. microcarpa germplasm that reflected the necessity for the conservation of this germplasm, and it is expected that the results gained in this study will assist current Cerasus breeding efforts and will maintain the genetic integrity of P. microcarpa.


Spatial-temporal differentiation of coupling coordination degree for green finance and green innovation efficiency: a case study in China.
Continued investment in finance and innovation is beneficial to economic development, and the joining of green system can accelerate the process of economic recovery from environmental distress. To better enhance the relationship of green finance and green innovation, it is vital to demonstrate the synergy between the two thoroughly. Thirty provinces in China are selected to examine the coupling coordination relationship between the two, specifically testing the spatial aggregation and evolutionary differences in the coupling coordination by adopting the coupling coordination degree (CCD) model, spatial autocorrelation, and kernel density estimation. Conclusions of the paper show that green finance is calculated by the EW-TOPSIS method, and the overall score of provinces is low. Using super-SBM model to evaluate green innovation, the uneven distribution of efficiency is obvious, although it is gradually increasing. The CCD in most provinces is in low-level or basic coordination, with significant regional heterogeneity. The global Moran's index becomes gradually evident with time. The local Moran scatter diagram presents a downward trend from east to west, but with more L-L aggregation provinces emerging in 2020. The center of the national kernel density curve gradually shifts to the right, indicating that the national overall synergy level is improving. Deepening the understanding of the empirical results facilitates the formulation of reasonable policies that fit the four major regions.


The inhibitory effects of Escherichia coli maltose binding protein on β-amyloid aggregation and cytotoxicity.
The aggregation of β-amyloid (Aβ) peptide from its monomeric to its fibrillar form importantly contributes to the development of Alzheimer's disease. Here, we investigated the effects of Escherichia coli maltose binding protein (MBP), which has been previously used as a fusion protein, on Aβ42 fibrillization, in order to improve understanding of the self-assembly process and the cytotoxic mechanism of Aβ42. MBP, at a sub-stoichiometric ratio with respect to Aβ42, was found to have chaperone-like inhibitory effects on β-sheet fibril formation, due to the accumulation of Aβ42 aggregates by sequestration of active Aβ42 species as Aβ42-MBP complexes. Furthermore, MBP increased the lag time of Aβ42 polymerization, decreased the growth rate of fibril extension, and suppressed Aβ42 mediated toxicity in human neuroblastoma SH-SY5Y cells. It appears that MBP decreases the active concentration of Aβ42 by sequestering it as Aβ42-MBP complex, and that this sequestration suppresses ongoing nucleation and retards the growth rate of Aβ42 species required for fibril formation. We speculate that inhibition of the growth rate of potent Aβ42 species by MBP suppresses Aβ42-mediated toxicity in SH-SY5Y cells.


Enhanced peroxidase-like activity of AuNPs loaded graphitic carbon nitride nanosheets for colorimetric biosensing.
Nanozymes have emerged as promising alternatives to overcome the high cost and low stability issues of natural enzymes. Particularly, those with peroxidase-like activities have been extensively studied to construct versatile biosensors. In this article, we demonstrate that the modification of the graphitic carbon nitride nanosheets (g-C3N4 nanosheets) by plasmonic gold nanoparticles (AuNPs) greatly enhances its catalytic performance as peroxidase mimetic. In the presence of H2O2, the AuNPs@g-C3N4 nanosheets can catalyze the redox reaction of 3,3',5,5'- tetramethylbenzidine (TMB) to produce a blue color. Based on the observation, a colorimetric sensing method for glucose is further developed with the assistance of glucose oxidase (GOx). The linear range for glucose is from 5 to 100 μmol L-1 (R2 = 0.9967) and the limit of detection (LOD) is 1.2 μmol L-1. The LOD can be further lowered down to 0.75 μmol L-1 by using H2SO4 as termination agent and measuring the absorbance of the yellow product at λ = 451 nm. Moreover, the practical usefulness of AuNPs@g-C3N4 nanosheets as a peroxidase nanozyme for glucose determination in human serum and urine is also demonstrated.


Genome-wide identification and functional analysis of S-RNase involved in the self-incompatibility of citrus.
S-RNase-based self-incompatibility is found in Solanaceae, Rosaceae, and Scrophulariaceae, and is the most widespread mechanism that prevents self-fertilization in plants. Although 'Shatian' pummelo (Citrus grandis), a traditional cultivated variety, possesses the self-incompatible trait, the role of S-RNases in the self-incompatibility of 'Shatian' pummelo is poorly understood. To identify genes associated with self-incompatibility in citrus, we identified 16 genes encoding homologs of ribonucleases in the genomes of sweet orange (Citrus sinensis) and clementine mandarin (Citrus clementine). We preliminarily distinguished S-RNases from S-like RNases with a phylogenetic analysis that classified these homologs into three groups, which is consistent with the previous reports. Expression analysis provided evidence that CsRNS1 and CsRNS6 are S-like RNase genes. The expression level of CsRNS1 was increased during fruit development. The expression of CsRNS6 was increased during the formation of embryogenic callus. In contrast, we found that CsRNS3 possessed several common characteristics of the pistil determinant of self-incompatibility: it has an alkaline isoelectric point (pI), harbors only one intron, and is specifically expressed in style. We obtained a cDNA encoding CgRNS3 from 'Shatian' pummelo and found that it is homolog to CsRNS3 and that CgRNS3 exhibited the same expression pattern as CsRNS3. In an in vitro culture system, the CgRNS3 protein significantly inhibited the growth of self-pollen tubes from 'Shatian' pummelo, but after a heat treatment, this protein did not significantly inhibit the elongation of self- or non-self-pollen tubes. In conclusion, an S-RNase gene, CgRNS3, was obtained by searching the genomes of sweet orange and clementine for genes exhibiting sequence similarity to ribonucleases followed by expression analyses. Using this approach, we identified a protein that significantly inhibited the growth of self-pollen tubes, which is the defining property of an S-RNase.


Study of prolonged hyposensitization with D. pteronyssinus extract in allergic rhinitis.
Sixty-six Chinese patients with rhinitis, with or without asthma, were randomly allocated to a course of injections either with E. pteronyssi-us extract or placebo. The course consisted of 18--22 weekly injections, followed by monthly maintenance injections with the highest concentration for 1 year. Progress was evaluated by a patient's daily diary and monthly assessments by the physician, by comparisons of skin and nasal challenge tests and by the specific serum IgE concentration, before treatment, at the end of the weekly course, and once during the maintenance course. No improvement was detected at the end of the weekly course, but during maintenance there was a consistent benefit to the patients receiving the D. pteronyssinus extract both in the diary and the physician's assessment, especially the former. There was no consistent change in the skin or nasal challenge tests and there was a trivial fall in the serum IgE levels in the patients on the extract. Adverse reactions were much more common in the patients on the extract, but most were trivial. The different methods of assessment used and the role of hyposensitization with D. pteronyssinus are discussed.


Endogenous pro-resolving and anti-inflammatory lipid mediators: the new hope of atherosclerotic diseases.
Atherosclerosis is a complex disease process in which genetic, lipid, cellular, and immunological factors combine to determine the location, severity, and timing of lesion development and clinical events. It has been demonstrated, however, that inflammation governed atherosclerosis during the course of development of atherosclerosis. It has also been demonstrated to be effective to decrease the cardiovascular events and improve the prognosis of atherosclerotic diseases by regulating inflammatory reaction (e.g., statins). However, endogenous mechanisms of limiting inflammation in atherosclerosis are still unclear. Recent studies showed that lipoxidase/leukotrienes (LOX/LTs) pathway played important role in the ignition and development of atherosclerosis, whereas resolvins (E-series resolvins and D-series resolvins) and protectins [protectin D1 (PD1) and neuroprotectin D1 (NPD1)], endogenous lipid-derived mediators, inhibited inflammation through pro-resolution and counter-modulating immune inflammation reaction in atherosclerosis. Hence, we hypothesize that increased endogenous lipid mediators mentioned above play a vital role in anti-atherosclerosis and plaque stabilization through pro-resolution and anti-inflammation by LOX/LTs pathway. In addition, we predict that the endogenous lipid mediators may be a new target for treatment of atherosclerotic diseases.


Stent effects on duplex velocity estimates.
Doppler-derived velocity criteria used to define the presence and severity of in-stent restenosis after percutaneous angioplasty and endoluminal stenting have been called into question. This study uses an in vitro flow model to examine Doppler-derived velocities after placement of balloon-expandable and self-expanding endoluminal stents (BES and SES). An in vitro vascular circuit model consisting of a pulsatile pump, tubing, and a conduit was created. The pump was programmed to replicate the Doppler spectral waveform pattern of the renal and carotid arteries. Peak systolic velocity (PSV) and end diastolic velocity (EDV) were estimated at five distinct conduit locations. Three replicate velocity measurements were made at each location. After initial velocity estimates, a BES or an SES was deployed within the conduit. Mean ± standard error PSV was 95.8 ± 2.6 cm/s, 97.0 ± 2.7 cm/s, and 101.4 ± 2.7 cm/s for unstented, BES and SES, respectively. PSV estimates were increased between unstented and stented conduits when SESs were present. The increase in mean systolic velocity of 6.4% observed with SES was statistically significant (P < 0.05). EDV values did not differ significantly across conditions. Mean ± standard error EDV was 36.2 ± 1.0 cm/s, 37.3 ± 1.1 cm/s, and 37.2 ± 1.1 cm/s for unstented, BES, and SES, respectively. The presence of an SES was associated with a less than 7% change in estimated PSV. These results suggest that Doppler velocity estimates for renal and carotid arteries are not materially affected by either BES or SES.


Seasonal variations of Rana esculenta L. skin tyrosinase.
Various enzymes are known to be involved in melanin biosynthesis, but the key role appertains to tyrosinase. In amphibians this enzyme displays peculiar characteristics: i) it requires an activation process; ii) its level of enzymatic activity in the animal skin changes depending on the season. In this work, by using chymotrypsin, subtilisin and SDS as putative activators, we studied the activation process of the skin pro-tyrosinase of Rana esculenta L. in different seasons over a period of two years. We found that chymotrypsin and subtilisin were able to yield an active enzyme, but not SDS. The maximum levels of tyrosinase activity were recorded in winter and the minimum in summer. We detected tyrosinase activity in the melanosomal fraction, where the enzyme form was least sensitive to proteolytic activation, probably corresponding to a "mature" tyrosinase. The enzyme forms found in the microsomal and soluble fractions were more sensitive to proteolytic activation, probably corresponding to "immature" tyrosinase. On SDS-PAGE, the tyrosinase activity assays showed a dopa-positive band at 200 kDa and a second aggregated band with a still higher molecular mass. The significance of these results in frog melanogenesis regulation is discussed.


Casein, a prohormone with an immunomodulating role for the newborn?
Maternal colostrum and milk, the earliest food of the newborn, should not only be considered as supplying nutrients, but also as agents providing protection against aggressions from the new environment. Indeed by enzymatic digestion of the main milk proteins, the caseins, biologically active peptides are released; they may be implicated in the stimulation of the newborn's immune system. From this point of view a 'strategic active zone' has been characterized in beta-casein. A possible role of casein as a 'prohormone' for the newborn is suggested.


Indoleamine and catecholamine concentrations in the mid-term human fetal brain.
Because of the likelihood that androgen-induced sex specific brain differentiation is mediated by various neurotransmitters, their concentrations were measured in the mid-term human fetal hypothalamus, cortex and cerebrospinal fluid (CSF). Tissue was collected from 32 hysterotomy specimens aged from 10 to 23 weeks, immediately frozen in liquid nitrogen, and stored at -20 degrees C. 5-Hydroxytryptamine (5-HT), 5-hydroxy indole acetic acid (5-HIAA), norepinephrine (NE) and dopamine (DA) levels were measured by a fluorometric assay. Cord serum testosterone levels were measured by radioimmunoassay. In the male fetuses, hypothalamic concentrations of 5-HT, 5-HIAA and NE were all significantly increased in comparison to those in the cortex. Because the number of female fetuses was small, only the 5-HIAA levels were seen to be significantly higher in the hypothalamus than in the cortex. In the CSF from fetuses of both sexes, the DA levels were greatly raised. Concentrations of NE were significantly higher in male fetuses aged from 14-16 weeks, a time when plasma testosterone levels are also elevated. It is hypothesized that the raised plasma testosterone and hypothalamic NE concentrations are inter-related.


Patterns of physical activity, sitting time, and sleep in Australian adults: A latent class analysis.
To identify the patterns of activity, sitting and sleep that adults engage in, the demographic and biological correlates of activity-sleep patterns and the relationship between identified patterns and self-rated health. Online panel of randomly selected Australian adults (n = 2034) completing a cross-sectional survey in October-November 2013. Panel members who provided complete data on all variables were included (n = 1532). Participants self-reported their demographic characteristics, height, weight, self-rated health, duration of physical activity, frequency of resistance training, sitting time, sleep duration, sleep quality, and variability in bed and wake times. Activity-sleep patterns were determined using latent class analysis. Latent class regression was used to examine the relationships between identified patterns, demographic and biological characteristics, and self-rated health. A 4-class model fit the data best, characterized by very active good sleepers, inactive good sleepers, inactive poor sleepers, moderately active good sleepers, representing 38.2%, 22.2%, 21.2%, and 18.4% of the sample, respectively. Relative to the very active good sleepers, the inactive poor sleepers, and inactive good sleepers were more likely to report being female, lower education, higher body mass index, and lower self-rated health, the moderately active good sleepers were more likely to be older, report lower education, higher body mass index and lower self-rated health. Associations between activity-sleep pattern and self-rated health were the largest in the inactive poor sleepers. The 4 activity-sleep patterns identified had distinct behavioral profiles, sociodemographic correlates, and relationships with self-rated health. Many adults could benefit from behavioral interventions targeting improvements in physical activity and sleep.


Effects of neuropeptides on gastric acid and duodenal bicarbonate secretions in freely moving rats.
The central nervous system effects of neuropeptides on gastric acid and duodenal bicarbonate secretions were examined. In freely moving rats, i.c.v. administration of thyrotropin-releasing hormone (TRH), human gastrin-17 (hG-17) and the somatostatin analogue, desAA 1,2,4,5,12,13 [D-Trp8]somatostatin (ODT8-SS), significantly increased gastric acid secretion, while vasoactive intestinal peptide (VIP) had no effect. In the order of potency and efficacy, the following peptides decreased acid secretion: bombesin (BOM) greater than calcitonin gene-related peptide (CGRP) greater than calcitonin (CT) greater than corticotropin-releasing factor (CRF) greater than beta-endorphin (beta-END) greater than neurotensin (NT). In anesthetized rats, none of these peptides significantly altered proximal duodenal bicarbonate secretion. In awake, freely moving rats, cerebroventricular administration of CGRP significantly decreased while ODT8-SS, TRH and CRF significantly increased duodenal bicarbonate secretion. beta-Endorphin, VIP, CT, BOM, NT and hG-17 given i.c.v. did not significantly alter the bicarbonate response. These results indicate that neuropeptides administered into the central nervous system modulate gastric acid as well as duodenal bicarbonate secretions in awake, freely moving rats in a differentiated fashion. CGRP inhibits both acid and bicarbonate secretions, a somatostatin analogue and TRH both stimulate acid and bicarbonate secretions and CRF inhibits gastric acid but stimulates duodenal bicarbonate secretions.


Efficacy of chlorhexidine bathing for reducing healthcare associated bloodstream infections: a meta-analysis.
We performed a meta-analysis of randomized controlled trials (RCTs) to determine if daily bathing with chlorhexidine decreased hospital-acquired BSIs in critically ill patients. We searched the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases to identify randomized controlled trials that compared daily bathing with chlorhexidine and a control in critically ill patients. This meta-analysis included five RCTs. The overall incidence of measured hospital-acquired BSIs was significantly lower in the chlorhexidine group compared to the controls 0.69 (95 % CI 0.55-0.85; P < 0.001; I (2) = 57.7 %). Gram-positive-induced (RR = 0.49, 95 % CI 0.41-0.58; P = 0.000; I (2) = 0.0 %) bacteremias were significantly less common in the chlorhexidine group. The incidence of MRSA bacteremias (RR 0.63; 95 % CI 0.44-0.91; P = 0.006; I (2) = 30.3 %) was significantly lower among patients who received mupirocin in addition to chlorhexidine bathing than among those who did not routinely receive mupirocin. Daily bathing with chlorhexidine may be effective to reduce the incidence of hospital-acquired BSIs. However, chlorhexidine bathing alone may be of limited utility in reduction of MRSA bacteremia; intranasal mupirocin may also be required. This meta-analysis has several limitations. Future large-scale international multicenter studies are needed.


Does Symptom Recognition Improve Self-Care in Patients with Heart Failure? A Pilot Study Randomised Controlled Trial.
Patients with heart failure have difficulty in self-care management, as daily monitoring and recognition of symptoms do not readily trigger an action to avoid hospital admissions. The purpose of this study was to understand the impact of a nurse-led complex intervention on symptom recognition and fluid restriction. A latent growth model was designed to estimate the longitudinal effect of a nursing-led complex intervention on self-care management and quality-of-life changes in patients with heart failure and assessed by a pilot study performed on sixty-three patients (33 control, 30 intervention). Patients in the control group had a higher risk of hospitalisation (IRR 11.36; p < 0.001) and emergency admission (IRR 4.24; p < 0.001) at three-months follow-up. Analysis of the time scores demonstrated that the intervention group had a clear improvement in self-care behaviours (βSlope. Assignment_group = -0.881; p < 0.001) and in the quality of life (βSlope. Assignment_group = 1.739; p < 0.001). This study supports that a nurse-led programme on symptom recognition and fluid restriction can positively impact self-care behaviours and quality of life in patients with heart failure. This randomised controlled trial was retrospectively registered (NCT04892004).


Going global: building a foundation for global health promotion research to practice.
Global health promotion is now becoming an integral part of foreign policy of many countries. Health Promotion Practice has always kept pace with changes in the field of health education and promotion. The Society for Public Health Education Board of Trustees and the Editorial Board of Health Promotion Practice are pleased to announce the launch of a new department, "Global Health Promotion." This introductory commentary for the new Global Health Promotion Department of Health Promotion Practice defines global health and the new challenges for health education and health promotion. The "ecology" of global health promotion is presented as a framework to initiate dialog and discussion. Global health domains and competencies are discussed as future directions. In this commentary, we also present our vision and mission for the department as we strive for linkages between research, practice, policy, and population health promotion through cross-cultural collaboration. A call for general and departmental submissions-in the form of original research papers, case studies, symposium reports, interviews, and other forms of interprofessional communication-is included to bridge research and practice in global health promotion.


The impact of delayed gastric emptying as measured by gastric emptying scintigraphy on the outcome of magnetic sphincter augmentation.
The impact of delayed gastric emptying (DGE) on the outcome of anti-reflux surgery (ARS) is controversial. There is concern that poor gastric emptying diminishes outcomes. Magnetic sphincter augmentation (MSA) may have a comparatively mild impact on gastric physiology, but the relationship between DGE and MSA outcomes is unknown. This study aims to evaluate the relationship between objective DGE and MSA outcomes over time. Patients who completed gastric emptying scintigraphy (GES) prior to MSA between 2013 and 2021 were included. DGE was defined as a 4 h retention > 10% or half emptying time > 90 min on GES. Outcomes were compared between DGE and normal gastric emptying (NGE) groups at 6 months, 1 and 2 years. Sub-analysis of patients with severe (> 35%) DGE and correlation analysis between 4-h retention and symptom and acid-normalization were performed. The study population consisted of 26 (19.8%) patients with DGE and 105 with NGE. DGE was associated with more 90-days readmissions (18.5 vs 2.9%, p = 0.009). At 6 months patients with DGE had higher median (IQR) GERD-HRQL total [17.0(10-29) vs 5.5(3-16), p = 0.0013], heartburn [1(1-3) vs 0(0-1), p = 0.0010) and gas-bloat [4(2-5) vs 2(1-3), p = 0.033] scores. Outcomes at 1 and 2 years follow-up were comparable (p > 0.05). From 6 months to 1-year the gas-bloat score decreased from 4(2-5) to 3(1-3), p = 0.041. Total and heartburn scores decreased, but not significantly. Severe DGE (n = 4) patients had lower antiacid medication freedom at 6 months (75 vs 87%, p = 0.014) and 1-year (50 vs 92%, p = 0.046). There were non-significant trends for higher GERD-HRQL scores, dissatisfaction, and removal rates in severe DGE at 6 months and 1-year. There was a weak correlation between 4-h retention and 6-month GERD-HRQL total score [R = 0.253, 95%CI (0.09-0.41), p = 0.039], but not acid-normalization (p > 0.05). Outcomes after MSA are diminished early on in patients with mild-to-moderate DGE, but comparable by 1 year and durable at 2 years. Severe DGE outcomes may be suboptimal.


Drug prescribing pattern in pregnancy in a secondary care hospital in south India: a retrospective study.
In pregnancy drug treatment presents a special concern due potential teratogenic effects and physiologic alterations in mother. This retrospective study was performed to evaluate the drug prescribing pattern in pregnancy among pregnant women in a secondary care hospital in India. This cross-sectional retrospective study was done for 3 months using pre-formatted forms and patient's records. A total of 326 drugs, including 46 different types of drugs, were prescribed to 606 gravid women. Eight different types of medications were started before being seen at the antenatal clinic. Most of these drugs fall under US FDA pregnancy categories B and C and few under categories A, X and N. This study reflects a good, safe and rational medication practice during pregnancy in various common disorders in a secondary care hospital and can be cited as an example to similar primary and secondary care hospitals.


Express photolithographic DNA microarray synthesis with optimized chemistry and high-efficiency photolabile groups.
DNA microarrays are a core element of modern genomics research and medical diagnostics, allowing the simple and simultaneous determination of the relative abundances of hundreds of thousands to millions of genomic DNA or RNA sequences in a sample. Photolithographic in situ synthesis, using light projection from a digitally-controlled array of micromirrors, has been successful at both commercial and laboratory scales. The advantages of this synthesis method are its ability to reliably produce high-quality custom microarrays with a very high spatial density of DNA features using a compact device with few moving parts. The phosphoramidite chemistry used in photolithographic synthesis is similar to that used in conventional solid-phase synthesis of oligonucleotides, but some unique differences require an independent optimization of the synthesis chemistry to achieve fast and low-cost synthesis without compromising microarray quality. High microarray quality could be maintained while reducing coupling time to a few seconds using DCI activator. Five coupling activators were compared, which resulted in microarray hybridization signals following the order ETT > Activator 42 > DCI ≫ BTT ≫ pyridinium chloride, but only the use of DCI led to both high signal and highly uniform feature intensities. The photodeprotection time was also reduced to a few seconds by replacing the NPPOC photolabile group with the new thiophenyl-NPPOC group. Other chemical parameters, such as oxidation and washing steps were also optimized. Highly optimized and microarray-specific phosphoramidite chemistry, along with the use of the very photosensitive thiophenyl-NPPOC protecting group allow for the synthesis of high-complexity DNA arrays using coupling times of 15 s and deprotection times of 9 s. The resulting overall cycle time (coupling to coupling) of about 50 s, results in a three-fold reduction in synthesis time.


Antibody-penicillin-V-amidase conjugates kill antigen-positive tumor cells when combined with doxorubicin phenoxyacetamide.
The two monoclonal antibodies (mAb), L6 (anti-carcinoma), and 1F5 [anti-(B-cell-lymphoma)], were chemically linked to the enzyme penicillin-V amidase (PVA), which hydrolyzes phenoxyacetamides, to explore the potential of using mAb-enzyme conjugates for the localization of chemotherapeutic drugs at tumor cells. The phenoxyacetamide derivatives of doxorubicin and melphalan were prepared, yielding the less toxic amides, doxorubicin-N-p-hydroxyphenoxyacetamide (DPO) and melphalan-N-p-hydroxyphenoxyacetamide (MelPO). These were hydrolyzed by PVA to doxorubicin and melphalan respectively. In vitro studies with the L6-positive lung carcinoma cell line, H2981, and the 1F5-positive B-cell lymphoma line, Daudi, showed that DPO was 80-fold less toxic to H2981 cells and 20-fold less toxic to Daudi cells than doxorubicin, and its toxicity was substantially increased when the H2981 cells were pretreated with L6-PVA or the Daudi cells were pretreated with 1F5-PVA. The cytotoxic effect was antigen-specific, since only the binding mAb-enzyme conjugate increased the cytotoxicity of the prodrug. MelPO was more than 1000-fold less toxic than melphalan to H2981 cells and more than 100-fold less toxic than melphalan to Daudi cells. Pretreatment with the mAb-PVA conjugates did not enhance the toxicity of MelPO in either cell line, because PVA hydrolyzes the phenoxyacetamide bond of MelPO too slowly to generate a toxic level of melphalan.


Computed tomographic scanning in liver disease.
The non-invasive diagnostic technique of computed tomograph (CT) has been assessed in 100 patients with established liver disease. CT can differentiate extra- from intrahepatic cholestasis and may define the obstructing lesion in the former group. It is of value in detecting infiltrations with fat or iron, and provides useful information in patients with cirrhosis and metastatic deposits. At present it appears of less value in the diagnosis of non-fibrotic parenchymal liver disease.