Effect of feed grade L-methionine on growth performance and gut health in nursery pigs compared with conventional DL-methionine.
Two experiments were conducted to test if supplementation of LMET has beneficial effects on growth performance and gut health in nursery pigs compared with DL-Met. In Exp. 1, 168 pigs in 56 pens were randomly allotted to 7 dietary treatments for 20 d, including a basal diet (BD; 55% of the NRC requirement for Met), the BD+0.048% L-Met or DL-Met (70% of the NRC requirement), the BD+0.096% L-Met or DL-Met (85% of the NRC requirement), and the BD+0.144% L-Met or DL-Met (100% of the NRC requirement). Body weight and feed disappearance were recorded every 5 d for computation of growth performance. In Exp. 2, 20 individually housed nursery pigs were randomly allotted to 2 dietary treatments for 20 d: DML (0.16% Met from the BD+0.145% supplemental DL-Met) or LMET (0.16% Met from the BD+0.145% supplemental L-Met). Both diets had Met meeting 95% of the NRC requirement. Duodenum samples from all pigs were collected at the end of the trial to evaluate morphology and redox status. In Exp. 1, during the entire 20 d, pigs fed diets supplemented with L-Met tended to have greater (P=0.087) ADG and reduced (P<0.01) plasma urea nitrogen (PUN) than pigs fed diets supplemented with DL-Met. The relative bioavailability (RBA) of L-Met to DL-Met for ADG and G:F was 143.8 and 122.7%, respectively. In Exp. 2, pigs fed a diet supplemented with L-Met had duodenum tissue with greater (P<0.05) concentrations of glutathione (GSH) and greater villus height and width as well as lower (P<0.05) concentrations of protein carbonyl compared with pigs fed DL-Met. Overall, compared with DL-Met, the use of L-Met as a source of supplemental Met in nursery pig diets enhanced duodenum villus development in association with reduced oxidative stress and improved GSH. The beneficial effects of supplementing L-Met compared to DL-Met in gut of nursery pigs resulted in a potential enhancement of ADG and reduction of PUN.


Isotropic 3-dimensional fast spin echo imaging versus standard 2-dimensional imaging at 3.0 T of the knee: artificial cartilage and meniscal lesions in a porcine model.
To compare different fat-saturated (FS) 3-dimensional (3D) intermediate-weighted (IM-w) fast spin echo (FSE) sequences with a standard FS 2-dimensional (2D) IM-w FSE sequence using a porcine in vitro model with artificially created cartilage and meniscus lesions. Using a ceramic scalpel, cartilage lesions with different depths and sizes were created in porcine knee specimens at the patella as well as the medial and lateral femoral and tibial cartilage. In addition, lateral and medial meniscal lesions were produced. Magnetic resonance imaging was performed at 3.0 T in sagittal plane using an 8-channel knee coil. A standard FS 2D IM-w FSE sequence and 3 newly developed isotropic 3D FSE sequences: (i) non-FS echo train length (ETL): 78, (ii) FS ETL: 44, and (iii) FS ETL: 44, were used. The images were independently analyzed by 4 radiologists concerning image quality (1 = optimal image quality, 4 = substantially limited quality) and absence or presence of lesions using a 5-level confidence score (1 = definite no presence of abnormality, 5 = definite presence of abnormality). Radiologists were also asked to measure diameter and categorize the depth of cartilage lesions using a modified Noyes classification. Average scores for image quality, confidence of diagnosis, and sensitivity, specificity, and accuracy were calculated. In addition, contrast-to-noise ratios were calculated. Image quality was significantly (P < 0.05) lower on the 3D FSE images than on the 2D FSE images [3D (i): 1.6 (SD, 0.43); 3D (ii): 2.35 (SD, 0.7); 3D (iii): 2.35 (SD, 0.5); 2D: 1.3 (SD, 0.35)]. No significant differences in diagnostic performance were found between 3D (i) and 2D FSE sequences. However, 16% fewer lesions were correctly detected with the 3D (ii) and (iii) sequences. Sensitivity was highest for the 2D sequence, and specificity was highest for the 3D (i) sequence. Confidence scores were higher for the 3D (i) sequence than for the 2D sequence. A significant increase (P < 0.05) in correctly measured cartilage lesions size and depth was found for the 3D (i) sequence over the standard 2D FSE sequence. Although the 3D FSE sequence performed better in depiction and characterization of cartilage abnormalities than the standard 2D FSE sequence, we currently do not recommend to use it as substitute. For the diagnosis of meniscal defects, however, no significant improvement was found.


Comparison of impulsive and premeditated perpetrators of intimate partner violence.
Violence occurs in four to five million intimate relationships each year in the United States. Past research has investigated the concept of batterer subtypes based on the nature of the violent behavior. To extend this research, the present study used the Impulsive/Premeditated Aggression Scale (IPAS) along with a battery of relevant self-report measures in a sample of men (N = 113) convicted of domestic violence and court ordered into an intervention program. Batterers whose violence was classified as premeditated scored higher on psychopathic traits and a measure of treatment rejection. Batterers whose violence was classified as impulsive in nature reported a wider range of serious psychopathology. It is suggested that the use of a bimodal classification (Impulsive/Premeditated) in batterers may have significant clinical and legal policy implications.


A gut feeling about insular seizures.
A 43-year-old man presented to the Prince of Wales Hospital, Sydney, New South Wales, Australia, after experiencing his first tonic-clonic seizure. For the previous 2 years he had undergone gastroenterological investigation of episodes of gagging associated with hypersalivation and lachrymation, occurring three or four times per week. EEG showed epileptiform discharges in the right anterior temporal region; brain MRI revealed a lesion in the right insular cortex. Video-EEG telemetry demonstrated that the episodes of gagging were focal seizures. Antiepileptic drug therapy resulted in no further episodes occurring over the next 10 months.


Localization of unlabeled bepirovirsen antisense oligonucleotide in murine tissues using in situ hybridization and CARS imaging.
Current methods for detecting unlabeled antisense oligonucleotide (ASO) drugs rely on immunohistochemistry (IHC) and/or conjugated molecules, which lack sufficient sensitivity, specificity, and resolution to fully investigate their biodistribution. Our aim was to demonstrate the qualitative and quantitative distribution of unlabeled bepirovirsen, a clinical stage ASO, in livers and kidneys of dosed mice using novel staining and imaging technologies at subcellular resolution. ASOs were detected in formalin-fixed paraffin-embedded (FFPE) and frozen tissues using an automated chromogenic in situ hybridization (ISH) assay: miRNAscope. This was then combined with immunohistochemical detection of cell lineage markers. ASO distribution in hepatocytes versus nonparenchymal cell lineages was quantified using HALO AI image analysis. To complement this, hyperspectral coherent anti-Stokes Raman scattering (HS-CARS) imaging microscopy was used to specifically detect the unique cellular Raman spectral signatures following ASO treatment. Bepirovirsen was localized primarily in nonparenchymal liver cells and proximal renal tubules. Codetection of ASO with distinct cell lineage markers of liver and kidney populations aided target cell identity facilitating quantification. Positive liver signal was quantified using HALO AI, with 12.9% of the ASO localized to the hepatocytes and 87.1% in nonparenchymal cells. HS-CARS imaging specifically detected ASO fingerprints based on the unique vibrational signatures following unlabeled ASO treatment in a totally nonperturbative manner at subcellular resolution. Together, these novel detection and imaging modalities represent a significant increase in our ability to detect unlabeled ASOs in tissues, demonstrating improved levels of specificity and resolution. These methods help us understand their underlying mechanisms of action and ultimately improve the therapeutic potential of these important drugs for treating globally significant human diseases.


Palliative management of gastric cancer.
Advanced gastric cancer and its palliative treatment have a long and interesting history. Today, gastric adenocarcinoma is the second leading cause of cancer death worldwide. Unfortunately, many cases are not diagnosed until late stages of disease, which underscores the importance of the palliative treatment of gastric cancer. Palliative care is best defined as the active total care of patients whose disease is not responsive to curative treatment. Although endoscopy is the most useful method for securing the diagnosis of gastric adenocarcinoma, computed tomography may be useful to assess local and distant disease. The main indication for the institution of palliative care is the presence of advanced gastric cancer for which curative treatment is deemed inappropriate. The primary goal of palliative therapy of gastric cancer patients is to improve quality, not necessarily length, of life. Four main modalities of palliative therapy for advanced gastric cancer are discussed: resection, bypass, stenting, and chemotherapy. The choice of modality depends on a variety of factors, including individual patient prognosis and goals, and should be made on case-by-case basis. Future directions include the discovery and development of serum or stool tumor markers aimed at prevention, improving prognostication and stratification, and increasing awareness and education.


Ropivacaine Induces Cell Cycle Arrest in the G0/G1 Phase and Apoptosis of PC12 Cells via Inhibiting Mitochondrial STAT3 Translocation.
STAT3 has neuroprotective effect via non-canonical activation and mitochondrial translocation, but its effect on ropivacaine-induced neurotoxicity remains unclear. Our previous study revealed that apoptosis was an important mechanism of ropivacaine-induced neurotoxicity; this study is to illustrate the relationship between STAT3 with ropivacaine-induced apoptosis. Those results showed that ropivacaine treatment decreased cell viability, induced cell cycle arrest in the G0/G1 phase, apoptosis, oxidative stress, and mitochondrial dysfunction in PC12 cells. Moreover, ropivacaine decreased the phosphorylated levels of STAT3 at Ser727 and downregulated the expression of STAT3 upstream gene IL-6. The mitochondrial translocation of STAT3 was also hindered by ropivacaine. To further illustrate the connection of STAT3 protein structure with ropivacaine, the autodock-vina was used to examine the interaction between STAT3 and ropivacaine, and the results showed that ropivacaine could bind to STAT3's proline site and other sites. In addition, the activator and inhibitor of mitoSTAT3 translocation were used to demonstrate it was involved in ropivacaine-induced apoptosis; the results showed that enhancing the mitochondrial STAT3 translocation could prevent ropivacaine-induced apoptosis. Finally, the expression of p-STAT3 and the levels of apoptosis in the spinal cord were also detected; the results were consistent with the cell experiment; ropivacaine decreased the expression of p-STAT3 protein and increased the levels of apoptosis in the spinal cord. We demonstrated that ropivacaine induced apoptosis by inhibiting the phosphorylation of STAT3 at Ser727 and the mitochondrial STAT3 translocation. This effect was reversed by the activation of the mitochondrial STAT3 translocation.


Thrombin-induced alterations in endothelial permeability.
Figure 15 summarizes the current understanding of mechanisms of endothelial permeability alterations induced with thrombin. If thrombin generation exceeds the antiprotease activity, thrombin results in clotting of fibrinogen and intravascular fibrin accumulation. Pulmonary neutrophil sequestration also occurs after fibrin deposition, and this is related to the degree and duration of fibrin sequestration. Neutrophil activation appears to be an essential requirement for the mediation of the pulmonary vascular injury. Thrombin-induced intravascular coagulation results in the generation of lipid mediators (LTB4 and HETEs), which may be involved in increasing endothelial permeability. The release of thrombin in higher concentrations during lysis of fibrin (sequence; see text) FIGURE 15. Hypothesis showing mechanisms of thrombin-induced increase in endothelial permeability to proteins. Thrombin may have direct effects on endothelial permeability, or thrombin induced fibrinogen clotting, activation of neutrophils, and the release of lipid metabolites that subsequently lead to an increase in endothelial permeability. clots may induce a direct formation of interendothelial "gaps." Therefore, the vascular injury induced by neutrophil activation and the formation of endothelial "gaps" induced directly by thrombin can both increase the endothelial permeability to proteins. Thrombin is an important mediator of increased endothelial permeability to macromolecules, and may participate in the inflammatory response. In this regard, thrombin may be similar to other mediators (such as histamine and serotonin) that have been previously documented to increase macromolecule transport across the endothelium. The implications of free thrombin in increasing endothelial permeability may be greater because thrombin not only has a direct effect on endothelial permeability, but also induces clotting of fibrinogen and the subsequent generation of mediators that activate neutrophils and that in turn can induce endothelial injury.


[Molecular pathology of multiple sclerosis and neuromyelitis optica].
Multiple sclerosis (MS) and neuromyelitis optica (NMO) are inflammatory demyelinating diseases of the central nervous system (CNS). The pathological hallmark of MS is sharply demarcated demyelinating plaques with the relative preservation of axons, suggesting autoimmune responses target CNS myelin. In contrast, NMO shows selective and severe attacks of both axons and myelin of the optic nerves and spinal cord, resulting in necrotic cavitation. Neuropathological studies have demonstrated extensive loss of aquaporin-4 (AQP4) and glial fibrillary acidic protein (GFAP) in NMO lesions, especially in perivascular areas of acute inflammatory lesions where immunoglobulins and activated complements are deposited. We recently demonstrated the extensive loss of connexins(Cxs) in active lesions of Baló's disease, MS and NMO. Early disruption of Cx gap junction among glial cells may be a common denominator in heterogeneous human demyelinating conditions. This review aims to discuss the molecular pathology of MS and NMO that have attracted the most attention in the recent years.


A Pediatric Case of Cowden Syndrome with Graves' Disease.
Cowden syndrome (CS) is a rare dominantly inherited multisystem disorder, characterized by an extraordinary malignant potential. In 80% of cases, the human tumor suppressor gene phosphatase and tensin homolog (PTEN) is mutated. We present a case of a 17-year-old boy with genetically confirmed CS and Graves' disease (GD). At the age of 15, he presented with intention tremor, palpitations, and marked anxiety. On examination, he had macrocephaly, coarse facies, slight prognathism, facial trichilemmomas, abdominal keratoses, leg hemangioma, and a diffusely enlarged thyroid gland. He started antithyroid drug (ATD) therapy with methimazole and, after a 2-year treatment period without achieving a remission status, a total thyroidectomy was performed. Diagnosis and management of CS should be multidisciplinary. Thyroid disease is frequent, but its management has yet to be fully defined. The authors present a case report of a pediatric patient with CS and GD and discuss treatment options.


Two synchronous malignant tumors of the pancreas: a case report.
Only a limited number of multiple synchronous primary malignancies of the pancreas have been reported in the medical literature. We report a case of two solid malignant tumors of the pancreas diagnosed preoperatively. We describe a 65-year-old Sri Lankan woman who presented with progressive obstructive jaundice. Initial contrast-enhanced computed tomography imaging detected a malignant tumor at the tail of her pancreas. A second tumor of the pancreatic head was detected with integrated imaging using multidetector computed tomography and multimodal magnetic resonance imaging. She underwent total pancreaticoduodenectomy and splenectomy. Gross examination of the specimen confirmed the presence of two separate tumors. Histology of the ampullary tumor showed pancreatic-type adenocarcinoma and the tumor in the tail of her pancreas showed a colloid-type adenocarcinoma. The possibility of multiple primary malignant solid tumors of different types with malignant potential has to be considered even without background pathology when managing multiple tumors in the pancreas.


Albumin is encoded by 2 messenger RNAs in Xenopus laevis.
A cDNA clone library was prepared from liver poly(A) RNA pf non-estrogenized Xenopus laevis. Albumin coding sequences were screened by hybridization to a cDNA prepared from poly(A) RNA enriched by sucrose density gradient centrifugation, and by a sensitive solid-phase radioimmunoassay to detect clones that contain templates for albumin antigenic determinants. Nine clones were obtained by this approach, and all but one have the cDNA inserted in phase with the beta-lactamase gene of pBR322. Mapping of these clones with restriction endonucleases yielded 2 distinct patterns, suggestive of heterogeneity in the coding sequences. This was confirmed by heteroduplex analyses of hybrids formed between clones representative of each of the 2 classes. Both classes of albumin cDNA clones were used to select mRNAs of the same size (2.3kb) that code for peptides that are indistinguishable by SDS gel electrophoresis. Examination of the organization of the albumin genes by blot hybridization of the cDNA clones to restriction fragments of Xenopus DNA failed to detect any differences at the genomic level. The considerable diversity of the albumin cDNAs is suggestive of a multiplicity of albumin genes, rather than differential processing of a common precursor RNA.


Polyoxometalatocyclophanes: controlled assembly of polyoxometalate-based chiral metallamacrocycles from achiral building blocks.
The first polyoxometalatocyclophanes have been synthesized by the covalent linkage of a hexamolybdate cluster and bisarylimido ligands containing flexible chains. These metallamacrocycles are chiral, and some of them can undergo spontaneous resolution. The work provides a new protocol for preparing chiral polyoxometalates (POMs) and chiral metallamacrocycles from achiral building blocks by fastening both ends of a flexible chain onto an achiral POM to remove the symmetric center and mirror.


[Protective effect and related mechanism of tanshinol borneol ester on homocysteine induced rat bone marrow mesenchymal stem cells damage].
Objective: To investigate the protective effect and potential mechanism of tanshinol borneol ester (TBE) on homocysteine(Hcy) induced rat bone marrow mesenchymal stem cells (BMSCs) damage. Methods: BMSCs were isolated and cultured in vitro by density gradient centrifugation and adherent culture method. BMSCs were divided into the control (normal isolation and culture), TBE-1(10 μmol/L TBE-1 solution with 100 μl), TBE-2 (10 μmol/L TBE-2 solution with 100 μl), Hcy (0.5 mmol/L Hcy solution with 100 μl), Hcy + TBE-1(0.5 mmol/L Hcy solution with 100 μl, and 10 μmol/L TBE-1 solution with 100 μl), Hcy + TBE-2 (0.5 mmol/L Hcy solution with 100 μl, and 10 μmol/L TBE-2 solution with 100 μl), Hcy+ TBE-1+ inhibitor group(0.5 mmol/L Hcy solution with 100 μl, 10 μmol/L TBE-1 solution with 100 μl, and 25 μmol/L LY294002(specific blocker of phosphatidylinositol 3 kinase) solution with 100 μl), Hcy+ TBE-2+ inhibitor group(0.5 mmol/L Hcy solution with 100 μl, 10 μmol/L TBE-2 solution with 100 μl, and 25 μmol/L LY294002 solution with 100 μl). Cell proliferation activity was detected by MTT assay. The T-SOD activity and malonaldehyde level of cells were measured by anthineoxidase method and TBA method, respectively, to evaluate cell oxidative and antioxidative activities. The ultrastructure of cells was observed under transmission electron microscope. The expression level of PKB and NF-κB of cells in various groups were detected with the immunocytochemical method. Results: (1)Cell proliferation activity in TBE-1 group and TBE-2 group was significantly increased compared with the control group (both P<0.01), and was similar between TBE-1 group and TBE-2 groups after 1, 12, 24 and 48 hours treatment.(2)The T-SOD activity in TBE-1 group and TBE-2 group was significantly higher than in control group (both P<0.01), while it was significantly lower in Hcy group, Hcy+ TBE-1 group, and Hcy+ TBE-2 group than in control group(all P<0.01), and was similar between control group, Hcy+ TBE-1+ inhibitor group, and Hcy+ TBE-2+ inhibitor group(all P>0.05). The T-SOD activity was higher in Hcy+ TBE-1 group and Hcy+ TBE-2 group than in Hcy group(both P<0.01), and was higher in Hcy+ TBE-1+ inhibitor group than in Hcy+ TBE-1 group(P<0.05) and was higher in Hcy+ TBE-2+ inhibitor group than in Hcy+ TBE-2 group(P<0.05). The malonaldehyde level was lower in TBE-1 group and TBE-2 group than in control group(both P<0.01), was higher in Hcy group, Hcy+ TBE-1 group, Hcy+ TBE-2 group, Hcy+ TBE-1+ inhibitor group, and Hcy+ TBE-2+ inhibitor group than in control group(all P<0.01), was lower in Hcy+ TBE-1 group and Hcy+ TBE-2 group than in Hcy group(both P<0.01), was higher in Hcy+ TBE-1+ inhibitor group than in Hcy+ TBE-1 group(P<0.05), was higher in Hcy+ TBE-2+ inhibitor group than in Hcy+ TBE-2 group(P<0.05). (3)Under electron microscope, BMSCs showed profound swelling, senescence and apoptosis of cells increased significantly in Hcy group, Hcy+ TBE-1+ inhibitor group, and Hcy+ TBE-2+ inhibitor group when compared with control group. BMSCs in the TBE-1 and TBE-2 groups presented with abundant rough endoplasmic reticulum, and very active cell metabolism signs. Compared with Hcy group, BMSCs edema, the number of aging and apoptotic cells, and cell injury severity were significantly less in TBE-1+ Hcy group and TBE-2+ Hcy. (4)The PKB level was higher in TBE-1 group and TBE-2 group than in control group(both P<0.01), was lower in Hcy group, Hcy+ TBE-2 group, Hcy+ TBE-1+ inhibitor group, and Hcy+ TBE-2+ inhibitor group than in control group(all P<0.01), was similar between control group and Hcy+ TBE-1 group(P>0.05), was higher in Hcy+ TBE-1 group and Hcy+ TBE-2 group than in Hcy group(both P<0.05), was lower in Hcy+ TBE-1+ inhibitor group than in Hcy+ TBE-1 group(P<0.05), and was lower in Hcy+ TBE-2+ inhibitor group than in Hcy+ TBE-2 group(P<0.05). The NF-κB level was higher in TBE-1 group and TBE-2 group than in control group(both P<0.01), was lower in Hcy group, Hcy+ TBE-1 group, Hcy+ TBE-2 group, Hcy+ TBE-1+ inhibitor group, and Hcy+ TBE-2+ inhibitor group than in control group(P<0.01 or 0.05), was higher in Hcy+ TBE-1 group and Hcy+ TBE-2 group than in Hcy group(both P<0.05), was lower in Hcy+ TBE-1+ inhibitor group than in Hcy+ TBE-1 group(P<0.05) and was lower in Hcy+ TBE-2+ inhibitor group than in Hcy+ TBE-2 group(P<0.05). Conclusion: Tanshinol borneol ester can promote the proliferation of BMSC, and attenuate the homocysteine induced rat BMSCs damage possibly through activation of phosphatidylinositol 3 kinase/PKB signal transduction and its downstream signal pathway protein NF-κB.


Hepatic lymphatics as opacified by percutaneous intrahepatic injection of contrast medium. Analysis of hepatic lymphograms in 125 cases.
Hepatic lymph vessels were opacified in 125 patients with various hepatobiliary diseases during percutaneous transhepatic cholangiography or portography. Contrast medium deposited in the parenchyma flowed relatively quickly in winding channels, usually toward the hepatic hilus. No correlation was demonstrated between the locus of the intraparenchymal deposit and the direction of the flow. Contrast medium also opacified the lymphatics near the hepatic hilus and abdominal aorta. Neither jaundice nor liver disorder were prerequisite for the visualization of the hepatic lymphatics. The intrahepatic injection of contrast medium provides a safe and useful method for the study of hepatic lymph and its pathways.


An improved preparation of bovine brain proteolipid.
An improved preparation of proteolipid from bovine brain white matter is described. The product obtained by repeated acetone precipitation is completely soluble in chloroform-methanol and has a fairly constant composition: 35% protein, 40% galactocerebroside, and about 25% phospholipid.


Trisomy 6q22 leads to 6qter due to maternal 6;21 translocation. Case report review of the literature.
Partial trisomy for the long arm of chromosome 6, involving 6q22 leads to 6qter, was observed in a 2-month-old male infant. The mother was 6q;21p translocation carrier. A review of the previously published cases with trisomies of different 6q segments suggests that the critical segment responsible for the clinically recognizable phenotype of 6q trisomy seems to be limited to bands 6q26 and/or 6q27.


Optimisation of Bjerkandera adusta culture conditions for the production of α-α-trehalose.
Several factors affect the vegetative growth of fungi, such as temperature, pH, and culture medium. In addition to mycelial growth, these factors affect metabolite production. There are limited studies that have identified the metabolites produced by the fungus Bjerkandera adusta, which have potential biotechnological applications. Here, we evaluated the effects of temperature, culture medium, and incubation time on the production of mycelial mass and metabolites of B. adusta isolated from Pinus taeda. The highest mycelial mass was obtained at 24 °C, in the potato dextrose and malt extract media, upon incubation for 28 and 35 days. The disaccharide α-α-trehalose was for the first time isolated and identified by X-ray diffraction in this fungal genus.


Mild Prolongation of Prothrombin Time Does Not Affect the Safety and Prognosis of Transjugular Intrahepatic Portal Shunt: Based on Real-World Data.
The aim was to investigate the safety and prognosis of transjugular intrahepatic portal shunt in patients with mildly prolonged prothrombin time. Two hundred fifty-three patients with portal hypertension who received transjugular intrahepatic portal shunt from November 2015 to May 2021 in Wuhan Union Hospital were retrospectively selected. According to the preoperative prothrombin time, they were divided into 2 groups: 126 patients in the non-clinical significance group (prothrombin time prolongation <3 seconds) and 127 patients in the clinical significance group (3 seconds ≤ prothrombin time prolongation <6 seconds). A line chart of postoperative liver and kidney function was drawn, and Kaplan-Meier curve was used to analyze and compare the prognosis of the 2 groups. Transjugular intrahepatic portal shunt was successfully performed in all patients; the technical success rate was 100%, and no puncture-related complications occurred during perioperative period. The mean preoperative prothrombin time was 14.9 ± 0.7 seconds in the non-clinical significance group and 17.2 ± 0.8 seconds in the clinical significance group. During follow-up, 1-year stent dysfunction rates in the non-clinical significance group and clinical significance group were 3.5% and 6.9%, respectively, with no statistically significant difference (hazard ratio = 0.77, 95% CI = 0.30-1.93, log-rank P = .575). In addition, there were no significant differences in the cumulative survival rate (log rank P = .255), rebleeding rate (log-rank P = .392), and incidence of hepatic encephalopathy (log-rank P = .404) between the 2 groups. Subgroup analysis of the clinical significance group showed no significant difference in safety and prognosis between the 2 subgroups. Transjugular intrahepatic portal shunt is safe for portal hypertension patients with prothrombin time prolongation <6 seconds. There was no significant difference in prognosis between the non-clinical significance group and the clinical significance group.


Choosing the Ideal Advanced Practice Leader for Your Organization.
This month's column highlights the attributes, competencies, and qualifications for consideration when selecting the ideal advanced practice leader, one that is collaborative and skilled in providing leadership at the executive or health systems level.


[Effect of d-limonene, Salvia miltiorrhiza and turmeric derivatives on membrane association of Ras gene product and gap junction intercellular communication].
Gap junction intercellular communication (GJIC), H-ras oncogene expression and Ras oncogene product(P21ras protein) expression were studied in four human solid tumor cell lines, W1-38, CACO2, A549 and PaCa (with the different Ras gene mutation rate), and the effects of four compounds, Salvia miltiorrhiza derivative (SMD), d-limonene, turmeric derivative I(TD-I) and turmeric derivative II(TD-II), on them. The abilities of the four solid tumor cell lines to transfer dye to adjacent cells were examined using the scrape-loading/dye transfer technique, and the H-ras oncogene expression by Northern blotting and P21ras protein expression by Western blotting. The results showed the loss of intercellular coupling in PaCa cells, slight GJIC in A549 and CACO2 cells, and good GJIC in W1-38 cells. The four compounds used was shown to improve the GJIC of PaCa to different extents. The amount of total and membrane associated P21ras in PaCa cells were decreased after treatment with SMD, d-limonene and TD-I(2.5 micrograms.ml-1) for 48 h. Concomitantly, the growth of PaCa cells decreased in soft agar and GJIC was enhanced. The relative potency was found to be: d-limonene > SMD > TD-I = TD-II. No significant effect of the four compounds on H-ras oncogene expression was observed. These results suggest that 1. there was an excellent correlation between loss of Lucifer Yellow dye transfer and ras gene mutation rate in the four solid tumor cell lines used (ras gene mutation rate inversely correlated with average cell number couplied, r = 0.98) i.e., showing that high ras gene mutation is closely correlated with loss of GJIC in these malignant human tumor cells; 2. the antitumor effect of the monoterpene d-limonene and the phenol compound, SMD, might be related to the inhibition of P21ras membrane association and enhancement of GJIC, whilst that of the others may be by a different mechanism; 3. the inhibition of P21ras membrane association is directly related to the enhancement of gap junction intercellular communication.


Pyrene cholesterol reports the transient appearance of nonlamellar intermediate structures during fusion of model membranes.
We have hypothesized that modulating the free energy of hydrophobic mismatch (HM) might be a principal means to control the fusion process and that it may be a role of cholesterol to counteract HM and make membranes fusogenic. To test these hypotheses, we examined the ability of cholesterol 1-pyrenebutyrate (PY-Ch) and other pyrene-containing fluorescent probes to report interstices formed during the L(alpha)-H(II) transition of DiPoPE in terms of changes in excimer/monomer (E/M) fluorescence ratios. We found a significant (>150%) increase in the PY-Ch E/M in the hexagonal phase relative to the lamellar phase, presumably resulting from redistribution of PY-Ch from the curved lamellar leaflets to coexisting HMs that constitute 20 vol % of this phase. All other probes showed a much smaller or even an opposite (PY-hexadecanoic acid) effect. The time course of the PY-Ch E/M ratio during fusion of DOPC/PE/Ch small unilamellar vesicles showed a transient increase with a subsequent decrease, consistent with fusion proceeding through intermediates with significant HM. The amplitude and position of the maximum in E/M correlated with the rate of contents mixing. An increase in E/M was not seen when lipid mixing occurred in the absence of contents mixing. Our results suggest that PY-Ch provides a tool for monitoring fusion intermediates that occur after the initial fusion intermediate but prior to pore formation, possibly by accumulating in regions associated with HM.


Renal denervation beyond the bifurcation: The effect of distal ablation placement on safety and blood pressure.
Renal denervation may be more effective if performed distal in the renal artery because of smaller distances between the lumen and perivascular nerves. The authors reviewed the angiographic results of 97 patients and compared blood pressure reduction in relation to the location of the denervation. No significant differences in blood pressure reduction or complications were found between patient groups divided according to their spatial distribution of the ablations (proximal to the bifurcation in both arteries, distal to the bifurcation in one artery and distal in the other artery, or distal to the bifurcation in both arteries), but systolic ambulatory blood pressure reduction was significantly related to the number of distal ablations. No differences in adverse events were observed. In conclusion, we found no reason to believe that renal denervation distal to the bifurcation poses additional risks over the currently advised approach of proximal denervation, but improved efficacy remains to be conclusively established.


The bread dough stability improving effect of pyranose oxidase from trametes multicolor and glucose oxidase from Aspergillus niger: unraveling the molecular mechanism.
Glucose oxidase (GO) and pyranose oxidase (P2O) improve dough stability and bread quality. We here studied whether their mode of action resides in cross-linking of proteins and/or arabinoxylan (AX) molecules through the production of H2O2. Evidence for both was deduced from a decrease in extractability of protein and AX from dough made with P2O, GO, or H2O2, using sodium dodecyl sulfate containing buffer and water, respectively. The addition of H2O2, P2O, or GO to a glutathione solution sharply decreased its sulfhydryl (SH) content. P2O or GO can trigger protein cross-linking through the formation of disulfide (SS) bonds. As a result thereof, SH/SS interchange reactions between low molecular mass SH containing compounds and gluten proteins can be hampered. Furthermore, a decrease in the level of monomeric ferulic acid (FA) esterified to AX in dough points to a role of FA bridges in cross-linking of AX molecules. Our results indicate that the molecular mechanism of dough and bread improvement by P2O and GO resides in cross-linking of gluten proteins and AX by formation of H2O2. They furthermore show that the extent of cross-linking upon addition of P2O or GO strongly depends on the concentration (and production rate) of H2O2.


SPECT vs. PET monitoring of bone defect healing and biomaterial performance in vivo.
Quantification of the bone healing processes by X-ray-based methods becomes inaccurate in the presence of radiopaque synthetic materials. In this study, single photon emission computed tomography (SPECT) and positron emission tomography (PET) were compared as alternatives to follow in vivo bone healing in a rat calvarial defect model. SPECT/computed tomography (CT) following administration of 99m technetium-labelled hydroxymethylene diphosphonate (99m Tc-HDP) and PET/CT data with 18 F-fluoride were acquired up to 10 weeks after surgery. New bone formation was then confirmed by histology. Computed tomography scans allowed visualization of untreated bone defect healing; however, no information was gathered in presence of the ceramic. Positron emission tomography provided superior data compared with SPECT. The 18 F-fluoride uptake increased significantly up to 4 weeks after surgery, declining thereafter until the last time-point. In vivo performances of porous versus dense ceramic scaffolds were also evaluated by PET, with a significantly higher uptake registered within the porous scaffolds. In conclusion, PET is a valuable tool for qualitative/quantitative follow-up of bone healing around radiopaque bone substitutes in vivo. Copyright © 2014 John Wiley & Sons, Ltd.


Guanylate-cyclase-inhibitory protein is a frog retinal Ca2+-binding protein related to mammalian guanylate-cyclase-activating proteins.
Two guanylate-cyclase-activating proteins (GCAP) encoded by a tail-to-tail gene array have been characterized in the mammalian retina. Using frog retina as a model, we obtained evidence for the presence of a photoreceptor Ca2+-binding protein closely related to GCAP. This protein (206 amino acids) does not stimulate guanylate cyclase (GC) in low [Ca2+], but inhibits GC in high [Ca2+], and is therefore termed guanylate-cyclase-inhibitory protein (GCIP). Sequence analysis indicates that GCIP and GCAP1 and GCAP2 have diverged substantially, but conserved domains present in all vertebrate GCAP are present in GCIP. Moreover, partial characterization of the GCIP gene showed that the positions of two introns in the GCIP gene are identical to positions of corresponding introns of the mammalian GCAP gene array. As to the major differences between GCIP and GCAP, the fourth EF hand Ca2+-binding motif of GCIP is disabled for Ca2+ binding, and GCIP does not stimulate GC. Monoclonal and polyclonal antibodies raised against recombinant GCIP identified high levels of GCIP in the inner segments, somata and synaptic terminals of frog cone photoreceptors. The results suggest that GCIP is a Ca2+-binding protein of the GCAP/recoverin subfamily. Its localization in frog cones closely resembles that of GC in mammalian cones. GCIP inhibits GC at high free [Ca2+], competing with GCAP1 and GCAP2 for GC regulatory sites.


[Undifferentiated soft tissue tumor with rhabdoid phenotype (extra-renal rhabdoid tumor). Report of a congenital case associated with medulloblastoma in a brother].
We report a case of congenital cervical rhabdoid tumor with association of a medulloblastoma in a brother. The immunohistochemical features of this tumor are compatible with a neuroectodermal differentiation (MIC 2+, Leu 7+). Extrarenal rhabdoid tumors share a common morphology but do not represent a single entity with only one histogenesis. Most of them are now considered to be of neuroectodermal origin. In our case, the association with a medulloblastoma in a brother seems to confirm this concept.


The first fluoride one-dimensional nanostructures: microemulsion-mediated hydrothermal synthesis of BaF2 whiskers.
A convenient microemulsion-mediated hydrothermal process was employed for the first synthesis of BaF2 whiskers with lengths up to 50 mum and aspects ratios as high as 1000, each of which is a single crystal with a growth direction of (111). A directed aggregation growth process mediated by the microemulsion droplet building blocks is proposed for the formation of BaF2 whiskers.


[Cerebral sinus thrombosis in a patient with protein S deficiency: a case report].
Cerebral sinus thrombosis associated with protein S deficiency is rare to the best of our knowledge. We report here a 22-year-old female who presented sudden onset of headache, vomiting and disturbance of consciousness. Neuroradiological studies including computed tomography scan, magnetic resonance imaging and cerebral angiography disclosed a huge cerebral sinus thrombosis in the territory of the superior sagittal sinus, torcular herophili, lateral sinus and straight sinus. Hematological studies confirmed the diagnosis of protein S deficiency. We summarize the reported cases of cerebral sinus thrombosis associated with protein S deficiency. For young patients presenting occlusive cerebrovascular disease, we stressed the importance of doing extensive hematological investigation to detect possible etiological factors, such as protein S deficiency, protein C deficiency, antithrombin III deficiency. Once we discover the etiology of a disease, we may be able to designate the precise treatment or regimen for each patient.


Pharmacokinetics of tulathromycin in fetal sheep and pregnant ewes.
Macrolides are important antimicrobials frequently used in human and veterinary medicine in the treatment of pregnant women and pregnant livestock. They may be useful for the control of infectious ovine abortion, which has economic, animal health, and human health impacts. In this study, catheters were surgically placed in the fetal vasculature and amnion of pregnant ewes at 115 (±2) days of gestation. Ewes were given a single dose of 2.5 mg/kg tulathromycin subcutaneously, and drug concentrations were determined in fetal plasma, maternal plasma, and amniotic fluid at 4, 8, 12, 24, 36, 48, 72, 144, and 288 hr after drug administration. Pharmacokinetic parameters in maternal plasma were estimated using noncompartmental analysis and were similar to those previously reported in nonpregnant ewes. Tulathromycin was present in fetal plasma and amniotic fluid, indicating therapeutic potential for use against organisms in these compartments, though concentrations were lower than those in maternal plasma. Time-course of drug concentrations in the fetus was quite different than that in the ewe, with plasma concentrations reaching a plateau at 4 hr and remaining at this concentration for the remainder of the sampling period (288 hr), raising questions about how tulathromycin may be transported into or metabolized and eliminated by the fetus.


Pharmacist-implemented pharmaceutical manufacturers' assistance programs: effects on health outcomes for seniors.
In the environment of rapidly mounting medication costs, pharmaceutical manufacturers' assistance programs (PMAPs) have become increasingly important in supplying medications to financially vulnerable patients. At Shenandoah Valley Compassionate Pharmacy, Winchester, Virginia, a nonprofit facility serving low-income seniors, a pharmacist and a patient advocate implement PMAPs by helping to enroll patients, dispensing medications, and providing patient counseling. To examine the effects of the program, we compared patients' clinical indicators before and after a 42-month intervention. Statistical analysis evaluated changes in clinical variables, such as systolic and diastolic blood pressure, glycosylated hemoglobin A1c, lipid panel (total cholesterol, low-density lipoprotein [LDL], highdensity lipoprotein [HDL], and triglycerides [TG]) for 84 seniors diagnosed with one or more chronic conditions. Results show statistically significant improvement in total cholesterol, LDL, and mean arterial pressure (calculated). TGs and A1c did not change significantly. In addition to dispensing free medications, the pharmacist provides counseling to enhance the efficacy of geriatric pharmacotherapy.


[Brain governing mind theory in traditional chinese medicine].
The "Heart Governing Mind" theory has been in the mainstream of visceral manifestation State Doctrine for a long time, but the "Brain Governing Mind" theory is also the traditional thought in Chinese culture. A large number of recordings about the brain in medical or non-medical books from Pre-Qin to the Qing dynasty reflected people's deeper and deeper understanding of the relation between the brain and mind. In order to provide a theoretical guidance for cerebral pathology, we should have a correct understanding of the important role of the brain in life activities, keep developing the "Brain Governing Mind" theory and understand the relationship between the brain and taiji, yinyang, wuxing, viscera, meridians and Guanqiao five apertures and nine orifices.


Can boron antisites of BNNTs be an efficient metal-free catalyst for nitrogen fixation? - A DFT investigation.
Nitrogen fixation is a challenging reaction under ambient conditions. So far, a few metal-based catalysts have been reported; however, noticeable disadvantages including high cost, gas poisoning, and them being hazardous to the environment are still to be resolved. We have carried out density functional theory based calculations with the ωB97X-D/6-31G* level of theory to investigate the activation of dinitrogen using boron nitride based metal-free catalysts for the first time as they are environmentally friendly and corrosion resistant. The boron antisite of a boron nitride nanotube is found to be an active site for nitrogen activation. The activated N2 is characterized by the increase in bond length and the red shift in the stretching frequency of the N[triple bond, length as m-dash]N bond. The subsequent reduction mechanisms of activated N2 into ammonia through six-proton and six-electron processes have also been elucidated. The selectivity of the nitrogen reduction reaction between distal and alternating associative pathways is also rationalized. The reaction energetics highlight the distal associative mechanism as a feasible pathway under ambient conditions. The catalytic performance of BAS is further unraveled with the help of variation in the charge density. This work provides a rational model for the metal-free catalytic conversion of N2 to ammonia via an eco-friendly pathway under ambient conditions.


Complete chloroplast genome assembly and phylogenetic analysis of blackcurrant (Ribes nigrum), red and white currant (Ribes rubrum), and gooseberry (Ribes uva-crispa) provide new insights into the phylogeny of Grossulariaceae.
Blackcurrant (Ribes nigrum), red currant (R. rubrum), white currant (R. rubrum), and gooseberry (R. uva-crispa) belong to Grossulariaceae and are popular small-berry crops worldwide. The lack of genomic data has severely limited their systematic classification and molecular breeding. The complete chloroplast (cp) genomes of these four taxa were assembled for the first time using MGI-DNBSEQ reads, and their genome structures, repeat elements and protein-coding genes were annotated. By genomic comparison of the present four and previous released five Ribes cp genomes, the genomic variations were identified. By phylogenetic analysis based on maximum-likelihood and Bayesian methods, the phylogeny of Grossulariaceae and the infrageneric relationships of the Ribes were revealed. The four cp genomes have lengths ranging from 157,450 to 157,802 bp and 131 shared genes. A total of 3,322 SNPs and 485 Indels were identified from the nine released Ribes cp genomes. Red currant and white currant have 100% identical cp genomes partially supporting the hypothesis that white currant (R. rubrum) is a fruit color variant of red currant (R. rubrum). The most polymorphic genic and intergenic region is ycf1 and trnT-psbD, respectively. The phylogenetic analysis demonstrated the monophyly of Grossulariaceae in Saxifragales and the paraphyletic relationship between Saxifragaceae and Grossulariaceae. Notably, the Grossularia subgenus is well nested within the Ribes subgenus and shows a paraphyletic relationship with the co-ancestor of Calobotrya and Coreosma sections, which challenges the dichotomous subclassification of the Ribes genus based on morphology (subgenus Ribes and subgenus Grossularia). These data, results, and insights lay a foundation for the phylogenetic research and breeding of Ribes species.


Lumboperitoneal shunt in idiopathic normal pressure hydrocephalus: a prospective controlled study.
In this prospective, controlled, monocentric study, we described the clinical and neuroimaging 12-month follow-up of two parallel cohorts of subjects with idiopathic normal pressure hydrocephalus (iNPH), who did or did not undergo lumboperitoneal shunt (LPS). We recruited 78 iNPH patients. At baseline, subjects underwent clinical and neuropsychological assessments, 3 T magnetic resonance imaging (MRI), and tap test. After baseline, 44 patients (LPS group) opted for LPS implantation, whereas 34 subjects (control group) declined surgery. Both cohorts were then followed up for 12 months through scheduled clinical and neuropsychological evaluations every 6 months. 3 T MRI was repeated at 12-month follow-up. Gait, balance, and urinary continence improved in the LPS group, without significant influence on cognitive functions. Conversely, gait and urinary continence worsened in the control group. No preoperative MRI parameter was significant outcome predictor after LPS. Of relevance, in responders to LPS, we found postoperative reduction of periventricular white matter (PWM) hyperintensities, which were instead increased in the control group. LPS is safe and effective in iNPH. An early surgical treatment is desirable to prevent clinical worsening. Post-surgery decrease of PWM hyperintensities may be a useful MRI marker surrogate for clinical effectiveness of LPS.


Development of fast steering mirror control system for plasma heating and diagnostics.
A control system for a fast steering mirror has been newly developed for the electron cyclotron heating (ECH) launchers in the large helical device. This system enables two-dimensional scan during a plasma discharge and provides a simple feedback control function. A board mounted with a field programmable gate array chip has been designed to realize feedback control of the ECH beam position to maintain higher electron temperature by ECH. The heating position is determined by a plasma diagnostic signal related to the electron temperature such as electron cyclotron emission and Thomson scattering.


Some variations of case-based techniques for the teaching of undergraduate pathology.
The challenges to the teaching of undergraduate pathology include adapting to the ever-evolving medical curriculum and the emergence of new teaching technologies. Nevertheless, pathology remains the crucial bridging medical discipline, with the pathology teacher playing an important role in consolidating the basic medical sciences and leading in the clinical disciplines. In this report, variations of case-based teaching of undergraduate pathology are discussed. These can be used in pathology lectures, tutorials and practical sessions, both traditional and computer-based. They contribute to the pathology teacher's repertoire of teaching tools and help add relevance and zest during class.


Permissive and restricted virus infection of murine embryonic stem cells.
Recent RNA interference (RNAi) studies have identified many host proteins that modulate virus infection, but small interfering RNA 'off-target' effects and the use of transformed cell lines limit their conclusiveness. As murine embryonic stem (mES) cells can be genetically modified and resources exist where many and eventually all known mouse genes are insertionally inactivated, it was reasoned that mES cells would provide a useful alternative to RNAi screens. Beyond allowing investigation of host-pathogen interactions in vitro, mES cells have the potential to differentiate into other primary cell types, as well as being used to generate knockout mice for in vivo studies. However, mES cells are poorly characterized for virus infection. To investigate whether ES cells can be used to explore host-virus interactions, this study characterized the responses of mES cells following infection by herpes simplex virus type 1 (HSV-1) and influenza A virus. HSV-1 replicated lytically in mES cells, although mES cells were less permissive than most other cell types tested. Influenza virus was able to enter mES cells and express some viral proteins, but the replication cycle was incomplete and no infectious virus was produced. Knockdown of the host protein AHCYL1 in mES cells reduced HSV-1 replication, showing the potential for using mES cells to study host-virus interactions. Transcriptional profiling, however, indicated the lack of an efficient innate immune response in these cells. mES cells may thus be useful to identify host proteins that play a role in virus replication, but they are not suitable to determine factors that are involved in innate host defence.


Leptin increases expression and activity of matrix metalloproteinase-2 and does not alter collagen production in rat glomerular mesangial cells.
Obesity is a leading risk factor for the development of nephropathy. In nephropathy, one of the major structural alterations found in the kidney is the increase in, or altered profile of, extracellular matrix (ECM) proteins such as collagen. Excessive synthesis and decreased degradation of matrix proteins by proteases such as matrix metalloproteinases (MMPs) may contribute to this process. We hypothesized that alterations observed in nephropathy may be due to alterations in direct effects of leptin, the product of the obesity gene. Here, we investigate the effect of leptin on collagen synthesis and MMP-2 production in rat glomerular mesangial cells. Using quantitative real-time PCR we showed that leptin does not alter the expression of collagen type I and IV mRNA. In keeping with this observation, proline incorporation was not altered by leptin. We also demonstrate that leptin induces MMP-2 expression in glomerular mesangial cells, assessed by quantitative real-time PCR. Analysis of conditioned media by gelatin zymography indicated increased activity at a molecular weight corresponding with that of MMP-2 in leptin-treated samples. In summary, our results indicate that leptin induces MMP-2 expression and activity without altering collagen synthesis, suggesting that normal leptin function has the potential to prevent ECM accumulation.


The impact of Helicobacter pylori eradication with vonoprazan-amoxicillin dual therapy combined with probiotics on oral microbiota: a randomized double-blind placebo-controlled trial.
Helicobacter pylori infection and eradication have been reported to cause dysbiosis of the oral microbiota. Probiotics are increasingly being used to maintain the balance of the oral microbiota. We aimed to investigate the effects of H. pylori infection, H. pylori eradication with vonoprazan-amoxicillin dual therapy, and probiotics supplementation on the oral microbiota. H. pylori positive patients were randomly assigned to a vonoprazan-amoxicillin regimen plus probiotics (BtT group) or the placebo (PT group) for 14 days. H. pylori negative population served as normal controls. Tongue coating samples were collected from 60 H. pylori positive patients at three time points (before H. pylori eradication, after H. pylori eradication, and at confirmation of H. pylori infection cure) and 20 H. pylori negative subjects. 16S rRNA gene sequencing was used to analyze the oral microbiota. H. pylori was detected in the oral cavity in positive (34/60), negative (7/20), and eradicated (1/60) subjects using high-throughput sequencing. Compared with normal controls, H. pylori positive patients exhibited higher richness (p = 0.012) and comparable diversity (p = 0.075) of oral microbiota. Beta diversity and KEGG analysis showed oral flora composition and function differences in H. pylori positive and negative subjects. Alpha diversity dramatically decreased after H. pylori eradication and modestly increased with confirmation of H. pylori eradication. Beta diversity and LEfSe analysis revealed distinct structures, and KEGG analysis showed distinct signaling pathways of tongue coating flora at three time points. There was a significant reduction of Firmicutes and Lactobacillus after H. pylori erdication. The PT group and BtT group had identical compositional and functional differences of oral microbiota at three time points. No substantial link existed between oral and stomach H. pylori, while removing gastric H. pylori helped eliminate oral H. pylori. H. pylori infection and vonoprazan-amoxicillin dual therapy affected oral microbiota diversity, structure, and function. H. pylori eradication demonstrated a suppressive impact on the proliferation of oral pathogens, specifically Firmicutes and Lactobacillus. Nevertheless, probiotics supplementation did not reduce the oral microbial disturbance caused by H. pylori eradication. https://www.chictr.org.cn/, identifiers CHICTR2200060023.


Caustic ingestion in adults--epidemiology and prevention.
A 16 year retrospective review identified 179 patients hospitalized for ingestion of caustic products in Aarhus County, Denmark. Seventy-five were adults over 15 years of age and residents of Aarhus County. The average annual incidence rate of hospitalization for caustic injury in adults was 1/100,000 with an incidence of esophageal burns of 0.8/100,000/y. Of the adults 61% attempted suicide: of these 61% were women. The annual incidence rate for adult women attempting suicide had an increasing trend (p = 0.048). Changes of the incidence rate for unintentional ingestions and for male suicide attempts were not significant. More than half of the suicide attempts were by patients with a history of a psychiatric illness. Of the caustics ingested by adults 94% were liquids. Acids accounted for 55% of the ingested products. Suicidal ingestion of hydrochloric acid was fatal in 6 of 12 adults. The inavailability of liquid caustics in the homes of patients at suicidal risk might prevent impulsive ingestion.


Gut microbiota and sepsis: bidirectional Mendelian study and mediation analysis.
There is a growing body of evidence that suggests a connection between the composition of gut microbiota and sepsis. However, more research is needed to better understand the causal relationship between the two. To gain a deeper insight into the association between gut microbiota, C-reactive protein (CRP), and sepsis, we conducted several Mendelian randomization (MR) analyses. In this study, publicly available genome-wide association study (GWAS) summary statistics were examined to determine the correlation between gut microbiota and sepsis, including various sepsis subgroups (such as under 75, 28-day death, Critical Care Units (ICU), 28-day death in ICU). Initially, two-sample and reverse Mendelian randomization (MR) analyses were conducted to identify causality between gut microbiota and sepsis. Subsequently, multivariable and two-step MR analyses revealed that the relationship between microbiota and sepsis was mediated by CRP. The robustness of the findings was confirmed through several sensitivity analyses. In our study, we revealed positive correlations between 24 taxa and different sepsis outcomes, while 30 taxa demonstrated negative correlations with sepsis outcomes. Following the correction for multiple testing, we found that the Phylum Lentisphaerae (OR: 0.932, p = 2.64E-03), class Lentisphaeria, and order Victivallales (OR: 0.927, p = 1.42E-03) displayed a negative relationship with sepsis risk. In contrast, Phylum Tenericutes and class Mollicutes (OR: 1.274, p = 2.89E-03) were positively related to sepsis risk and death within 28 days. It is notable that Phylum Tenericutes and class Mollicutes (OR: 1.108, p = 1.72E-03) also indicated a positive relationship with sepsis risk in individuals under 75. From our analysis, it was shown that C-reactive protein (CRP) mediated 32.16% of the causal pathway from Phylum Tenericutes and class Mollicutes to sepsis for individuals under 75. Additionally, CRP was found to mediate 31.53% of the effect of the genus Gordonibacter on sepsis. Despite these findings, our reverse analysis did not indicate any influence of sepsis on the gut microbiota and CRP levels. The study showcased the connection between gut microbiota, CRP, and sepsis, which sheds new light on the potential role of CRP as a mediator in facilitating the impact of gut microbiota on sepsis.


Bacterial and fungal aerosols in air-conditioned office buildings in Warsaw, Poland--the winter season.
The microbial quality of the working environment was assessed in winter in air-conditioned office buildings in Warsaw. The average indoor concentrations of bacterial and fungal aerosols were low (<10³ cfu·m⁻³), below Polish proposals for threshold limit values in public service buildings. Even during cold months, if the air-conditioning system works properly, people remain the main source of bacterial aerosol in offices, whereas infiltration of outdoor air remains a major mechanism responsible for their fungal contamination. An analysis of the bioaerosol size distribution showed that microbial propagules that reach both the upper and lower respiratory tract may evoke numerous adverse health effects from irritation and asthmatic reactions to allergic inflammation. A comparative analysis of viable and total airborne microbial counts showed that viable micro-organisms accounted for up to 0.3% of the total number of microbial propagules. Hence, a comprehensive hygienic assessment of office workplaces should include an efficient control of both these elements.


[Risk factors for and prognostic value of multifocal atherosclerosis in patients with diabetes mellitus].
To study the prognostic value of multifocal atherosclerosis (MFA) in patients with diabetes mellitus (DM) at high risk for myocardial ischemia who need coronary angiography (CAG). The investigation included 148 patients: 25 with type 1 DM (DM1), 73 with type 2 DM (DM2), and 50 without DM who had undergone CAG. Duplex ultrasound scanning of lower limb vessels and brachiocephalic and renal arteries was carried out in all the patients. Involvement of two or more vascular beds was noted in 60% of the patients with DM1, in 68.4% of those with DM2, and in 34% of those without DM (p < 0.05). Regression analysis showed that the risk factors of MFA were defined to be myocardial infarction (MI) in the history (OR=2.4; p=0.02), DM (OR=3.9; p=0.0002), smoking (OR=2.4; p=0.05), elevated creatinine (OR=6.5; p=0.002) and fibrinogen (OR=6.8, p=0.004) levels. Among the DM patients, there were 26.5% of those who had achieved a main assessment criterion (a combined end point (CEP)), such as death, urgent hospitalization for heart failure, nonfatal MI, nonfatal stroke, lower extremity amputation, double creatinine levels, and achievement of end-stage renal failure during a 24-month follow-up. In patients without carbohydrate metabolic disturbances, this indicator was 12% (p=0.01). During the prospective study, a total of 6.1% of patients died in the DM group; all the patients in the non-DM group completed the study. Calculation of survival rates by the Kaplan-Meier method indicated that the DM patients with concurrent atherosclerotic lesion had achieved CEP significantly more frequently than the comparison group. Such differences were absent among the persons without carbohydrate metabolic disturbances. The regression analysis has shown that prior MI, DM, smoking, creatinine and fibrinogen levels are factors associated with the development of MFA in the examined groups. In the patients with DM, concurrent atherosclerosis of two or more vascular beds is an important factor for the progression of cardiovascular and renal diseases.


[Reagents for modification of protein-nucleic complexes. III. Site-specific photomodification of elongation complex of DNA polymerase beta with arylazide derivatives of primers sensitized with fluorescent ATP gamma-amide].
ATP gamma-amides containing in gamma-N-position 1-methylpyrene, 9-methylanthracene, 10-chloro-9-methylanthracene, and 3-methylperylene residues were synthesized and characterized. These compounds were used as sensitizers of site-specific photomodification of the reconstituted elongating complex of the mammalian DNA polymerase beta. The photomodification was carried out with the use of photoaffine reagents, which were synthesized in situ by the 5'-(32)P-labeled primers extension with photoactive analogues of dCTP containing in the exo-N-position of cytosine various perfluoroarylazide groups. The effect of structures of the sensitizers and photoactive reagents on the efficiency and selectivity of photolinking of primers to the enzyme and template, as well as formation of a number of other photomodification products was studied. It was shown that the sensitizers containing 10-chloro-9-methylanthracene and 3-methylperylene residues allow preparation of photolinks in such irradiation conditions when photomodification in their absence is not essentially observed.


Thermocleavable materials for polymer solar cells with high open circuit voltage-a comparative study.
The search for polymer solar cells giving a high open circuit voltage was conducted through a comparative study of four types of bulk-heterojunction solar cells employing different photoactive layers. As electron donors the thermo-cleavable polymer poly-(3-(2-methylhexyloxycarbonyl)dithiophene) (P3MHOCT) and unsubstituted polythiophene (PT) were used, the latter of which results from thermo cleaving the former at 310 degrees C. As reference, P3HT solar cells were built in parallel. As electron acceptors, either PCBM or bis-[60]PCBM were used. In excess of 300 solar cells were produced under as identical conditions as possible, varying only the material combination of the photo active layer. It was observed that on replacing PCBM with bis[60]PCBM, the open circuit voltage on average increased by 100 mV for P3MHOCT and 200 mV for PT solar cells. Open circuit voltages approaching 1 V were observed for the PT:bis[60]PCBM solar cells and a maximum conversion efficiency of 1.3% was obtained for solar cells with P3MHOCT:PCBM as the photoactive material. For the reference solar cells maximum efficiencies of 2.1 and 2.4% were achieved for P3HT:PCBM and P3HT:bis[60]PCBM, respectively. Despite special measures taken in terms of substrate design and device processing, a substantial spread in the photovoltaic properties was generally observed. This spread could not be correlated with the optical properties of the solar cells, the thickness of the photo active layer or the electrode deposition conditions of the aluminum top electrode.


Developments in associative theory: A tribute to the contributions of Robert A. Rescorla.
The field of associative learning theory was forever changed by the contributions of Robert A. Rescorla. He created an organizational structure that gave us a framework for thinking about the key questions surrounding learning theory: what are the conditions that produce learning?, what is the content of that learning?, and how is that learning expressed in performance? He gave us beautifully sophisticated experimental designs that tackled deep theoretical problems in experimentally clever and elegant ways. And he left us with a collection of work that fundamentally altered the way we as a field think about basic learning processes. Few scientists have impacted their field in the way that Rescorla impacted animal learning theory. In this paper, we introduce this special issue (Developments in Associative Theory: A Tribute to Robert A. Rescorla) by considering some of the many ways in which Rescorla's empirical and theoretical contributions impacted learning theory over his almost 50-year career. We conclude by identifying multiple fundamental issues we think he would have found especially fruitful to pursue as we continue to move forward. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Reproductive failure of dominant males in the poeciliid fish Limia perugiae determined by DNA fingerprinting.
Hierarchical structures among male individuals in a population are frequently reflected in differences in aggressive and reproductive behavior and access to the females. In general, social dominance requires large investments, which in turn then may have to be compensated for by high reproductive success. However, this hypothesis has so far only been sufficiently tested in small mating groups (one or two males with one or two females) due to the difficulties of determining paternity by conventional methods. DNA fingerprinting overcomes these problems by offering the possibility to determine genetic relationships and mating patterns within larger groups [Burke, T. (1989) Trends Ecol. Evol. 4, 139-144]. We show here that in the poeciliid fish Limia perugiae, in small mating groups the dominant male has a mating success of 100%, whereas in larger groups its contribution to the offspring unexpectedly drops to zero.


Self-reported health, lifestyle and social circumstances of Australian adult cancer survivors: A propensity score weighted cross-sectional study.
With the prevalence of cancer survivors increasing, their unique needs must be better understood. We examined the health, lifestyles and social circumstances of adults with and without a history of cancer. We performed a cross-sectional study, using exposure and outcome data from the baseline survey (2006-2009) of participants in the 45 and Up Study, a prospective cohort study in New South Wales, Australia. We compared 20,811 cancer registry-verified adult cancer survivors with 207,148 participants without a history of cancer using propensity score weighting and accounting for multiple testing. The propensity weighting included age, sociodemographic factors and number of self-reported co-morbidities. Cancer survivors were more likely to report poorer physical and psychological health and quality of life compared to those without a cancer history, with most deficits still evident more than 10 years after cancer diagnosis. Cancer survivors were more likely to have a higher body mass index, but were less likely to smoke. Cancer survivors had greater functional limitations, including sexual, and were less likely to work full time, volunteer and spend time outdoors. Their social connectedness was, however, similar. Those with haematological cancer, lung cancer, or distant metastases, and those diagnosed at an older age, had the greatest health deficits and functional limitations. A history of cancer is associated with poorer health and less paid and unpaid work. Our findings reinforce the importance of routine long-term, integrated multidisciplinary care for cancer survivors and indicate the subgroups with the greatest unmet needs.


Pharmacokinetics and pharmacodynamics of growth hormone-releasing peptide-2: a phase I study in children.
Administration of GH-releasing peptide-2 (GHRP-2) represents a potential mode of therapy for children of short stature with inadequate secretion of GH. Requisite information to determine the dosing route and frequency for GHRP-2 consists of the pharmacokinetics (PK) and pharmacodynamics (PD) for this compound, neither of which have been previously evaluated in children. The purpose of this study was to characterize the PK and PD of GHRP-2 in children with short stature. Ten prepubertal children (nine boys and one girl; 7.7 +/- 2.4 yr old) received a single 1 microg/kg i.v. dose of GHRP-2 over 1 min, followed by repeated (n = 9) blood sampling over 2 h. GHRP-2 and GH were quantitated by specific RIA methods. PK parameters were calculated from curve fitting of GHRP-2 and GH vs. time data. Posttreatment plasma GH concentrations (normalized for pretreatment values) were used as the effect measurement. PD parameters were generated using the sigmoid Emax model. Disposition of GHRP-2 best fit a biexponential function. GHRP-2 PK parameters (mean +/- SD) were: alpha = 13.4 +/- 9.7 h(-1), beta = 1.3 +/- 0.3 h(-1), t(1/2beta) = 0.55 +/- 0.14 h, AUC(0-infinity) = 2.02 +/- 1.37 ng/mL x h, Cmax = 7.4 +/- 3.8 ng/mL, plasma clearance = 0.66 +/- 0.32 L/h x kg, and apparent volume of distribution = 0.32 +/- 0.14 L/kg. PK parameters for GH were: appearance rate constant = 5.9 +/- 3.1 h(-1), elimination t(1/2) = 0.37 +/- 0.15 h, lag time = 0.05 +/- 0.01 h, Cmax = 50.7 +/- 17.2 ng/mL, Tmax = 0.42 +/- 0.16 h, and AUC(0-infinity) = 47.9 +/- 26.1 ng/mL x h. PD parameters for GHRP-2 were: Ke0 = 1.13 +/- 0.94 h(-1), gamma = 13.15 +/- 9.44, E0 = 6.63 +/- 4.86 ng/mL (GH), Emax = 67.5 +/- 23.5 ng/mL (GH), and EC50 = 1.09 +/- 0.59 ng/mL. We concluded that 1) GHRP-2 produced a predictable and significant (i.e. compared to pretreatment values) increase in plasma GH concentrations; 2) the PK-PD link model enabled quantitative assessment of GHRP-2 modulation of serum GH levels; and 3) definition of the EC50 for GHRP-2 will enable PD and PK evaluations of extravascular dosing regimens for children.


Identification of triple-negative breast cancer cell lines classified under the same molecular subtype using different molecular characterization techniques: Implications for translational research.
The original algorithm that classified triple-negative breast cancer (TNBC) into six subtypes has recently been revised. The revised algorithm (TNBCtype-IM) classifies TNBC into five subtypes and a modifier based on immunological (IM) signatures. The molecular signature may differ between cancer cells in vitro and their respective tumor xenografts. We identified cell lines with concordant molecular subtypes regardless of classification algorithm or analysis of cells in vitro or in vivo, to establish a panel of clinically relevant molecularly stable TNBC models for translational research. Gene expression data were used to classify TNBC cell lines using the original and the revised algorithms. Tumor xenografts were established from 17 cell lines and subjected to gene expression profiling with the original 2188-gene algorithm TNBCtype and the revised 101-gene algorithm TNBCtype-IM. A total of six cell lines (SUM149PT (BL2), HCC1806 (BL2), SUM149PT (BL2), BT549 (M), MDA-MB-453 (LAR), and HCC2157 (BL1)) maintained their subtype classification between in vitro and tumor xenograft analyses across both algorithms. For TNBC molecular classification-guided translational research, we recommend using these TNBC cell lines with stable molecular subtypes.


The association between ragged or incomplete membranes and postpartum haemorrhage: A retrospective cohort study.
The association between an incomplete placenta and postpartum haemorrhage (PPH) is well documented; however, the significance of ragged or incomplete membranes has not been explored as an independent risk factor for PPH. To explore the association between the completeness of the amniotic and chorionic membranes and the risk of PPH, independent to placental status. 37 176 birth records were retrospectively extracted from the period 1 July, 2008 to 30 June, 2016 from the databases of two public hospitals in Melbourne, Australia. Following application of specific exclusion and inclusion criteria, including non-complete placentas, 5718 records were available for analysis. These records were grouped based on membrane status (complete, ragged or incomplete) and outcome (PPH or no PPH). Primary PPH rates were 14.8% in women with complete membranes, 20.2% in women with ragged membranes and 25.8% in women with incomplete membranes. Following statistical adjustment, the risk ratios for PPH were 1.32 (95% CI: 1.15-1.50) and 1.70 (95% CI: 1.41-2.04) in women with ragged and incomplete membranes, respectively. Both ragged and incomplete membranes were found to be independent risk factors for primary PPH. This previously un-discussed association has the potential to influence clinical practice changes, particularly with regard to the ongoing clinical relevance and use of the terms 'ragged' and 'incomplete' membranes.


Congenital cystic disease of the liver: isotope scanning, ultrasonography and angiography.
The radioisotope scanning, ultrasonic and angiographic findings in 16 patients with congenital cystic liver disease are described. Radioisotope scans are useful in determining the size, location and number of lesions. Ultrasonography is of value in differentiating solid from fluid-filled lesions, thus narrowing the differential diagnosis. At angiography, cysts produced well-defined avascular areas in the hepatogram in all 14 patients examined, enhanced by a well-defined "rim sign" in seven. This sign is considered pathognomonic of a cystic lesion (hydatid or congenital). Two had a "honeycomb" pattern at angiography, pathognomonic of congenital polycystic liver disease.


HIV Infection and Incidence of Cardiovascular Diseases: An Analysis of a Large Healthcare Database.
Background People living with HIV ( PLWH ) experience higher risk of myocardial infarction ( MI ) and heart failure ( HF ) compared with uninfected individuals. Risk of other cardiovascular diseases ( CVD s) in PLWH has received less attention. Methods and Results We studied 19 798 PLWH and 59 302 age- and sex-matched uninfected individuals identified from the MarketScan Commercial and Medicare databases in the period 2009 to 2015. Incidence of CVD s, including MI , HF , atrial fibrillation, peripheral artery disease, stroke and any CVD -related hospitalization, were identified using validated algorithms. We used adjusted Cox models to estimate hazard ratios and 95% CI s of CVD end points and performed probabilistic bias analysis to control for unmeasured confounding by race. After a mean follow-up of 20 months, patients experienced 154 MI s, 223 HF , 93 stroke, 397 atrial fibrillation, 98 peripheral artery disease, and 935 CVD hospitalizations (rates per 1000 person-years: 1.2, 1.7, 0.7, 3.0, 0.8, and 7.1, respectively). Hazard ratios (95% CI ) comparing PLWH with uninfected controls were 1.3 (0.9-1.9) for MI , 3.2 (2.4-4.2) for HF , 2.7 (1.7-4.0) for stroke, 1.2 (1.0-1.5) for atrial fibrillation, 1.1 (0.7-1.7) for peripheral artery disease, and 1.7 (1.5-2.0) for any CVD hospitalization. Adjustment for unmeasured confounding led to similar associations (1.2 [0.8-1.8] for MI , 2.8 [2.0-3.8] for HF , 2.3 [1.5-3.6] for stroke, 1.3 [1.0-1.7] for atrial fibrillation, 0.9 [0.5-1.4] for peripheral artery disease, and 1.6 [1.3-1.9] for CVD hospitalization). Conclusions In a large health insurance database, PLWH have an elevated risk of CVD , particularly HF and stroke. With the aging of the HIV population, developing interventions for cardiovascular health promotion and CVD prevention is imperative.


Effects of legal mechanisms on perceived coercion and treatment adherence among persons with severe mental illness.
This study takes preliminary steps to examine the effects of 2 legal mechanisms-outpatient commitment (OPC) and representative payeeship (rep payee)-on perceived coercion and treatment adherence in persons with severe mental illness (SMI). Data were collected in structured interviews from 258 involuntarily-admitted inpatients with SMI who were followed for 1 year after discharge. Subjects' clinicians and family members were also interviewed. The analyses show that subjects with both OPC and a rep payee perceived their mental health treatment to be significantly more coercive than subjects who did not receive these legal interventions. Duration of OPC and having a newly-appointed rep payee were both significantly associated with increased treatment adherence over the course of 1 year. For treatment-adherent subjects, neither form of legal mechanism was associated with perceived coercion in treatment, whereas subjects who were nonadherent perceived legal mechanisms as significantly more coercive. The data suggest that these legal tools both affect adherence to treatment, but when used together significantly increase the perceived coerciveness of treatment. Questions remain concerning the underlying mechanism of these effects.


Vertebroplasty versus Active Control Intervention for Chronic Osteoporotic Vertebral Compression Fractures: The VERTOS V Randomized Controlled Trial.
Background Evidence regarding percutaneous vertebroplasty (PV) for chronic painful osteoporotic vertebral compression fractures (OVCFs) remains limited. Purpose To compare pain relief, quality of life, and disability between PV and active control (anesthetic infiltration) interventions for chronic OVCF. Materials and Methods This prospective randomized clinical trial was conducted between May 2013 and June 2019 in participants with pain due to OVCF lasting longer than 3 months with bone marrow edema present at MRI. Study participants were randomly assigned to undergo PV (n = 40) or active control intervention (n = 40). The primary outcome was pain severity, assessed with the visual analog scale (VAS) (range, 0-10) during 12 months after treatment. Secondary outcomes included Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO) score (range, 0-100) and Roland Morris Disability Questionnaire (RMDQ) score (range, 0-100). Outcomes were analyzed according to a longitudinal multilevel model used to test the difference between groups in change from baseline across follow-up. Results The mean age of the 80 participants (54 women) was 69 years ± 10 (SD) in the PV group and 71 years ± 10 in the active control group. VAS score was 7.6 (95% CI: 7.0, 8.2) in the PV group and 7.3 (95% CI: 6.9, 7.8) in the active control group at baseline (P = .47) and 3.9 (95% CI: 3.1, 4.8) and 5.1 (95% CI: 4.3, 6.0), respectively, at month 12 (P = .045). At month 12, the group difference from baseline was 1.3 (95% CI: 0.1, 2.6; P = .02) for VAS, 5.2 (95% CI: 0.9, 9.4; P = .02) for QUALEFFO, and 7.1 (95% CI: -3.3, 17.5; P = .18) for RMDQ, favoring the PV group. Conclusion In the treatment of pain caused by chronic OVCFs, PV is more effective for pain relief and quality of life improvement than anesthetic injection alone, with similar improvement for disability between the groups. Clinical trial registration no. NCT01963039 © RSNA, 2023 See also the editorial by Beall and De Leacy in this issue.


Mapping bacteria on filter membranes, an innovative SERS approach.
The existence of pathogenic bacteria in drinking water has been a threat to the safety of human well-being. Traditional methods to detect bacteria are standard plate counts or rapid methods such as ELISA and PCR. However, those methods can be time-consuming or require pre-enrichment when detecting low concentrations of bacteria. Filter membrane has been used for bacteria collection and culturing when monitoring environmental water samples. In this study, we applied surface enhanced Raman spectroscopy (SERS) to rapidly screen bacteria cells on a filter membrane based on the unique signal from an indicator molecule, 4-mercaptophenylboronic acid (4-mpba), that can specifically bind to the surface of bacteria through diol group in its structure and give off consistent SERS signal. With a pore size of 0.22 μm, the filter membrane functions as both a concentrating device and a separation mechanism that eliminates molecules smaller than the pore size. With SERS mapping, 4-mpba gives characteristic signal, indicating the presence of bacteria, whereas no 4-mpba signal was observed in the absence of bacteria. The developed method can detect Escherichia coli, Salmonella enterica, and Listeria monocytogenes on a filter membrane non-selectively in 80 min. Application of the method in pond water was demonstrated. However, this method may not be able to discriminate between live and dead bacterial cells and further development is needed.


Effectiveness of a WeChat Combined Continuous Flash Glucose Monitoring System on Glycemic Control in Juvenile Type 1 Diabetes Mellitus Management: Randomized Controlled Trial.
Smartphones have received increasing attention and achieved positive outcomes in diabetes intervention. The widespread use of WeChat in China provides an opportunity for self-management practices in patients with diabetes. Nevertheless, how to combine the strengths of the WeChat platform with traditional medical strategy remains to be explored. This study aimed to evaluate the efficacy of a novel flash glucose monitoring device combined with the WeChat platform in juvenile type 1 diabetes management. A total of 60 juvenile patients with type 1 diabetes were randomly assigned into three groups: a blood glucose self-monitoring group (group A), a flash glucose monitoring (group B), and a flash glucose monitoring combined WeChat-interactive management group (group C). The intergroup differences in demographics, biochemical indicators, and questionnaire scores of the Diabetes Monitoring and Treatment Satisfaction Questionnaire and Diabetes Specific Quality of Life assessment were compared at the baseline and after 6 months. After the 6-month intervention, groups B and C showed significantly lower glycated hemoglobin A1c (HbA1c) levels compared to those observed at baseline (both P <0.05), with the largest decrease observed in group C (group B vs group C, P =0.04). Hypoglycemic episodes per month decreased from baseline in groups B and C (both P <0.05) and were more significant in group C (P <0.001). In addition, the DMTSQ scores increased in the 6th month in all groups (all P <0.05), and the largest rise in scores was found in group C, followed by groups B and A. The DQOL scores in groups B and C decreased significantly from the baseline (both P <0.05), with no change in group A. Flash glucose monitoring combined with the WeChat-interactive system may help achieve sustained glycemic control and higher satisfaction in patients with juvenile type 1 diabetes. This study was registered at chictr.org.cn, number ChiCTR1900025495. Registered 29 August 2019.


Adherence factors of Lactobacillus in the human gastrointestinal tract.
Despite the increasing number of scientific reports describing adhesion of Lactobacillus to components of the human intestinal mucosa, information on the surface molecules mediating this adhesion and their corresponding receptors is fragmentary. This MiniReview compiles present knowledge of the genetically and functionally characterized Lactobacillus factors responsible for mediating adhesion to different components of the human gastrointestinal tract. In addition, for the proteins among these factors, the domain structure is discussed, and where appropriate the results of in silico analyses are reported.


Inactivation of the ribonucleic acid-processing enzyme ribonuclease E blocks cell division.
The Escherichia coli endoribonuclease ribonuclease E, the enzyme responsible for the processing of precursor 5S ribosomal ribonucleic acid (RNA) from the nascent ribosomal RNA transcript, is thermolabile in rne-3071 mutants. When cells of such a strain were shifted to a nonpermissive temperature, the function of ribonuclease E was almost instantaneously inactivated. However, a threefold linear increase in absorbance took place over a 3-h period, and similar linear increases occurred in all the macromolecules we measured, including deoxyribonucleic acid, RNA, protein, and lipopolysaccharides. Interestingly, during this period, the cells elongated but failed to divide. Thus, these experiments suggest that an early effect of inactivation of the RNA processing enzyme ribonuclease E is a block in cell division.


Heterogeneity of human glioblastoma: glutathione-S-transferase and methylguanine-methyltransferase.
The DNA repair and detoxifying enzymes, O(6)-methylguanine-DNA-methyltransferase (MGMT) and glutathione-S-transferase (GST), may be responsible fpr poor response to alkylating agents in glioblastoma treatment. The methylation of MGMT promoter and the expression of MGMT and GST were highly heterogeneous in surgical specimens of human glioblastoma and in established human glioblastoma cells under 2-D and 3-D culture conditions, suggesting an intrinsic property of these cells. MGMT and GST expression did not predict the sensitivity of glioblastoma cells to alkylating agents. Combination of alkylating agents with inhibitors of GST disclosed additive effects, suggesting that inhibition of GST should be considered in glioblastoma therapy.


Short- and long-term effects of manipulation of the pineal/melatonin axis in ewes.
The experiments which have provided insight into the role of the pineal gland and melatonin in sheep reproduction are reviewed. There is now strong evidence that timed daily melatonin administration and continuous administration via implants are equally effective in promoting the same physiological consequences as short daylength. Thus melatonin treatments lasting six weeks can result in an advance of the breeding season and an advance in the seasonal peak in ovulation rate. Much longer periods of exposure to melatonin or long-term pinealectomy result in a different response. In the second part of this review the long-term effects of pineal manipulation in juvenile and pubertal ewes are compared and contrasted. Five years after pinealectomy (at 7.5 months) ewes displayed normal timed breeding seasons without exhibiting a normal annual pattern of LH sensitivity to oestradiol. Pinealectomy at 2.5 months of age resulted in delayed puberty and breeding seasons out of synchrony with normal ewes two years later. These animals maintained an LH sensitivity to oestradiol consistent with their own breeding season. Melatonin implants which delivered melatonin for over a year caused similar effects as pinealectomy at 2.5 months but had essentially opposite effects to pinealectomy in adults. These results generate many questions about the different perception of the melatonin signal in prepubertal versus adult ewes and the factors involved in the onset and offset of the breeding season.


[Nerve block for the treatment of chronic pain].
Nerve block is useful for the treatment of acute pain and cancer pain; however the treatment's effectiveness with regard to non-cancer chronic pain is controversial. Of the non-cancer diseases, trigeminal neuralgia and spinal facet joint pain, in which long-term pain relief can be obtained by the nerve block without serious complications in most of patients, are well suited for the nerve block. Systemic reviews for the treatment of radicular pain from spine disorders with the nerve block showed contradictory long-term results. In other chronic pains, the effectiveness of nerve blocks has not been proved, although anecdotal reports suggests that a small proportion of patients respond well to the nerve block. Further study is necessary to examine what kinds of pains and patients will be relieved with the nerve block.


Advances in Diagnosis and Multidisciplinary Management of Oropharyngeal Squamous Cell Carcinoma: State of the Art.
During the past decade and a half, the most common cause of oropharyngeal squamous cell carcinoma (OPSCC) has shifted from tobacco and alcohol to the human papillomavirus (HPV). HPV-driven p16-positive OPSCC and tobacco-related OPSCC differ in their underlying molecular and genetic profiles, socioeconomic demographics, and response to treatment. HPV-related OPSCC tends to occur in younger patients and has a significantly better response to treatment and excellent prognosis. The stark contrast in prognosis-with around 90% overall 5-year survival for HPV-related p16-positive OPSCC and 40% for non-HPV-related p16-negative OPSCC-has prompted major changes in the eighth edition of the staging manual of the AJCC (American Joint Committee on Cancer). The past 10-15 years have also witnessed major advances in surgery, radiation therapy (RT), and systemic therapy. Minimally invasive surgery has come of age, with transoral robotic procedures and laser microsurgery. Intensity-modulated RT (IMRT) and more recently proton-beam RT have markedly improved the conformity of RT, with an ability to precisely target the cancer and cancer-bearing regions while sparing normal structures and significantly reducing long-term treatment-related morbidity. Progress in systemic therapy has come in the form of immunotherapy and targeted agents such as cetuximab. Owing to the better prognosis of HPV-driven OPSCC as well as the morbidity associated with treatment, de-escalation of therapy via multiple strategies is being explored. The article reviews the advances in diagnosis and multidisciplinary management of OPSCC in the HPV era.©RSNA, 2019.


Nerve branches to the anterior tibial artery: Clinical application.
Arteries receive vascular branches (VBs) from peripheral nerves. VBs are thought to be involved in arterial constriction. Although the anterior tibial artery (ATA) receives VBs, information on their branching patterns and distribution areas remains limited. The aim of this study was to investigate the anatomical structures of the VBs reaching the ATA. Forty cadaver limbs were examined to assess the branching patterns and distribution areas of the VBs reaching the ATA. The VBs reaching the ATA ramified from the deep fibular nerve (DFN), and the ATA received two or three VBs in each limb. The following mean distances from the head of fibula to the points at which the VBs reached the ATA were measured: all the VBs, 1st VB, 2nd VB and 3rd VB. The measurements were 51.5 ± 23.2 mm, 33.3 ± 3.7 mm, 53.3 ± 18.6 mm, and 72.2 ± 24.5 mm, respectively. In all limbs, the DFN and the ATA converged after the DFN branched into the 1st VB. The 2nd VB in 38 of 40 limbs and the 3rd VB in 20 of 32 limbs were distributed in the ATA proximal to the convergence point of the ATA and the DFN. These findings revealed that all VBs reaching the ATA ramified from the DFN in all limbs. The ATA received two or three VBs, and all the 1st VBs distributed to the ATA proximal to the convergence point.


Chaperone Proteins in the Central Nervous System and Peripheral Nervous System after Nerve Injury.
Injury to axons of the central nervous system (CNS) and the peripheral nervous system (PNS) is accompanied by the upregulation and downregulation of numerous molecules that are involved in mediating nerve repair, or in augmentation of the original damage. Promoting the functions of beneficial factors while reducing the properties of injurious agents determines whether regeneration and functional recovery ensues. A number of chaperone proteins display reduced or increased expression following CNS and PNS damage (crush, transection, contusion) where their roles have generally been found to be protective. For example, chaperones are involved in mediating survival of damaged neurons, promoting axon regeneration and remyelination and, improving behavioral outcomes. We review here the various chaperone proteins that are involved after nervous system axonal damage, the functions that they impact in the CNS and PNS, and the possible mechanisms by which they act.


Increased NFAT5 expression stimulates transcription of Hsp70 in preeclamptic placentas.
We investigated the expression of heat shock protein 70 (Hsp70), nuclear factor of activated T cells 5 (NFAT5), and hypoxia-induced factor-1α (HIF-1α) in the placentas of normal and preeclamptic pregnancies and in human placental hypoxia models in vitro to examine the regulatory mechanisms of placental Hsp70 expression. The expression levels of HIF-1α, NFAT5, and Hsp70 were examined in placental samples from 10 females with preeclampsia and 10 normotensive control patients and in human choriocarcinoma trophoblast cells treated with 1 mM CoCl2 by western blotting. Using models of placental hypoxia, pharmacological inhibition of HIF-1α with chetomin and shRNA knockdown and overexpression of NFAT5 were performed to investigate the roles of HIF-1α and NFAT5 in induction of Hsp70 by placental hypoxia. The levels of HIF-1α, NFAT5, and Hsp70 expression were significantly higher in the preeclamptic compared to normal placentas. In the placental hypoxia models, the expression of HIF-1α, NFAT5, and Hsp70 were significantly higher after 3, 6, and 12 h of 1 mM CoCl2 treatment, respectively. Pharmacological inhibition of HIF-1α suppressed the induction of NFAT5 and Hsp70 at the protein level. shRNA knockdown of NFAT5 suppressed the induction of Hsp70 protein and overexpression of NFAT5 stimulated the induction of Hsp70 mRNA and protein in models of human placental hypoxia in vitro. HIF-1α positively regulates the induction of NFAT5 and Hsp70 by placental hypoxia and NFAT5 stimulates transcription of Hsp70 in response to placental hypoxia in models of human placental hypoxia in vitro.


Randomized controlled trial of OnTrack, a just-in-time adaptive intervention designed to enhance weight loss.
Individual instances of nonadherence to reduced calorie dietary prescriptions, that is, dietary lapses, represent a key challenge for weight management. Just-in-time adaptive interventions (JITAIs), which collect and analyze data in real time to deliver tailored interventions during moments of need, may be well suited to promote weight loss by preventing dietary lapses. We developed OnTrack (OT), a smartphone application (app) that collects data on lapses and triggers of lapse, uses a continuously improving machine learning model to predict lapse risk, and delivers tailored interventions when risk is elevated. The current study evaluated the efficacy of OT against an active control in facilitating weight loss. Participants (N = 181) with overweight/obesity (MBMI = 34.32; 85.1% female; 73.5% White) were randomized to receive either the WW (formerly Weight Watchers) Beyond the Scale (BTS) digital program alone or WW plus OnTrack (WW + OT) for 10 weeks. In an unplanned, natural experiment, the WW program changed mid-way through the trial from BTS to a more flexible one, Freestyle (FS). A general linear model revealed a treatment condition × diet plan interaction (F[1, 173] = 9.68, p = .002) such that OT demonstrated greater efficacy only among those receiving BTS (weight loss MWW + OT = 4.7%, standard error [SE] = .55 versus MWW = 2.6%, SE = .80). Compared to FS, BTS WW + OT participants also reported considerably higher satisfaction with the intervention, engagement was higher, and algorithm accuracy was superior. Overall, results offer qualified support for OT and generally for machine learning-powered JITAIs that facilitate weight loss by predicting and preventing dietary lapses.


Unresectable pancreatic tumour? The issue is tissue.
The majority of tumours in the pancreas are adenocarcinomas for which therapeutic options are limited and which are associated with an unsatisfactory prognosis. However, alternative diagnoses may result in other therapeutic approaches with often a more favourable outcome. Hence, it is crucial to obtain a histological diagnosis before a definitive therapeutic plan can be devised. In this manuscript, a small series of pancreatic tumours other than adenocarcinoma are described.


Function of the nucleus accumbens in motor control during recovery after spinal cord injury.
Motivation facilitates recovery after neuronal damage, but its mechanism is elusive. It is generally thought that the nucleus accumbens (NAc) regulates motivation-driven effort but is not involved in the direct control of movement. Using causality analysis, we identified the flow of activity from the NAc to the sensorimotor cortex (SMC) during the recovery of dexterous finger movements after spinal cord injury at the cervical level in macaque monkeys. Furthermore, reversible pharmacological inactivation of the NAc during the early recovery period diminished high-frequency oscillatory activity in the SMC, which was accompanied by a transient deficit of amelioration in finger dexterity obtained by rehabilitation. These results demonstrate that during recovery after spinal damage, the NAc up-regulates the high-frequency activity of the SMC and is directly involved in the control of finger movements.