Postnatal developmental consequences of altered insulin sensitivity in female sheep treated prenatally with testosterone.
Prenatally testosterone (T)-treated female sheep exhibit ovarian and endocrinological features that resemble those of women with polycystic ovarian syndrome (PCOS), which include luteinizing hormone excess, polyfollicular ovaries, functional hyperandrogenism, and anovulation. In this study, we determined the developmental impact of prenatal T treatment on insulin sensitivity indexes (ISI), a variable that is affected in a majority of PCOS women. Pregnant ewes were treated with 60 mg testosterone propionate intramuscularly in cottonseed oil two times a week or vehicle [control (C)] from days 30 to 90 of gestation. T-females weighed less than C-females or males (P < 0.05) at birth and at 5 wk of age. T-females had an increased anogenital ratio. An intravenous glucose tolerance test followed by an insulin tolerance test conducted after an overnight fast at 5, 20, and 30 wk of age (n = 7-8/group) revealed that ISI were higher at 5 than 30 wk of age in C-females, reflective of a developing insulin resistance associated with puberty. T-females had higher basal insulin levels, higher fasting insulin-to-glucose ratio, and higher incremental area under the insulin curve to the glucose challenge. The ISI of T-females was similar to that of males. No differences in ISI were evident between groups at 20 and 30 wk of age. Mean basal plasma glucose concentrations and glucose disappearance and uptake did not differ between groups at any age. Our findings suggest that prenatal T treatment leads to offspring with reduced birth weight and impaired insulin sensitivity in early postnatal life.


Age-related changes in the reducible cross-links of human dermis collagen.
Samples of normal human dermis of different ages are reduced with tritiated sodium borohydride and changes of major reducible cross-links are compared as a function of chronological age. While lysinorleucine practically remains constant, reduced desmosine changes slightly, hydroxylysinoroleucine and dihydroxylysinonorleucine display a marked decrease with age. An unknown compound is shown to increase with aging. The data suggest a correlation between the change of aldimine cross-links and the structural and/or biochemical changes occurring with increase in age.


Emergency department sonographic measurement of optic nerve sheath diameter to detect findings of increased intracranial pressure in adult head injury patients.
Our objective is to determine whether a bedside ultrasonographic measurement of optic nerve sheath diameter can accurately predict the computed tomographic (CT) findings of elevated intracranial pressure in adult head injury patients in the emergency department (ED). We conducted a prospective, blinded observational study on adult ED patients with suspected intracranial injury with possible elevated intracranial pressure. Exclusion criteria were age younger than 18 years or obvious ocular trauma. Using a 7.5-MHz ultrasonographic probe on the closed eyelids, a single optic nerve sheath diameter was measured 3 mm behind the globe in each eye. A mean binocular optic nerve sheath diameter greater than 5.00 mm was considered abnormal. Cranial CT findings of shift, edema, or effacement suggestive of elevated intracranial pressure were used to evaluate optic nerve sheath diameter accuracy. Fifty-nine patients were enrolled in the study. Average age was 38 years, and median Glasgow Coma Scale score was 15 (interquartile 6 to 15). Eight patients with an optic nerve sheath diameter of 5.00 mm or more had CT findings that correlated with elevated intracranial pressure. The sensitivity for the ultrasonography in detecting elevated intracranial pressure was 100% (95% confidence interval [CI] 68% to 100%) and specificity was 63% (95% CI 50% to 76%). The sensitivity of ultrasonography for detection of any traumatic intracranial injury found by CT was 84% (95% CI 60% to 97%) and specificity was 73% (95% CI 59% to 86%). Bedside ED optic nerve sheath diameter ultrasonography has potential as a sensitive screening test for elevated intracranial pressure in adult head injury.


A 6-month safety and efficacy study of fluticasone propionate and fluticasone propionate/salmeterol multidose dry powder inhalers in persistent asthma.
A novel multidose dry powder inhaler (MDPI) that is breath actuated, easy, and intuitive to use has been developed for administering fluticasone propionate (Fp) and Fp/salmeterol (FS). To assess the safety and efficacy of Fp MDPI versus Fp hydrofluoroalkane (HFA) and FS MDPI versus FS dry-powder inhaler (DPI). This phase III, 26-week, open-label, active drug-controlled study enrolled subjects ≥12 years old with persistent asthma. Based on entry controller medication (inhaled corticosteroid [ICS] or ICS/long-acting beta-agonist), the subjects were randomized to twice-daily mid-strength Fp MDPI 100 μg or Fp HFA 220 μg, high-strength Fp MDPI 200 μg or Fp HFA 440 μg, mid-strength FS MDPI 100/12.5 μg or FS DPI 250/50 μg, or high-strength FS MDPI 200/12.5 μg or FS DPI 500/50 μg in a 3:1 MDPI to Fp HFA or FS DPI ratio. Safety and efficacy were assessed by adverse events (AE) and pulmonary function and asthma symptoms, respectively. A total of 674 subjects were randomized. The AE incidence was similar across treatment groups (upper respiratory tract infections, sinusitis, and nasopharyngitis were most frequent). A higher percentage of subjects in the Fp HFA 440 μg and FS DPI 500/50 μg groups had oral candidiasis versus those who received Fp MDPI 200 μg or FS MDPI 200/12.5 μg, respectively. Serious AEs were similar between the treatments, with no unexpected findings. The incidence of asthma exacerbations was low and generally similar between the groups. Noninferiority was established for all Fp MDPI and FS MDPI doses compared with Fp HFA and FS DPI, respectively, for forced expiratory volume in 1 second. Changes in peak expiratory flow, rescue albuterol use, and symptoms were similar between treatments. The safety and efficacy profiles of Fp MDPI and FS MDPI administered at lower doses were generally comparable with those of Fp HFA and FS DPI, respectively, after 26 weeks of treatment.The ClinicalTrials.gov identifier is NCT02175771.


Vacuum-UV irradiation-based formation of methyl-Si-O-Si networks from poly(1,1-dimethylsilazane-co-1-methylsilazane).
The vacuum-UV (VUV)-induced conversion of commercially available poly(1,1-dimethylsilazane-co-1-methylsilazane) into methyl-Si-O-Si networks was studied using UV sources at wavelengths around 172, 185, and 222 nm, respectively. Time-of-flight secondary ion mass spectroscopy (TOF-SIMS), X-ray photo electron spectroscopy (XPS), and Fourier transform infrared (FTIR) measurements, as well as kinetic investigations, were carried out to elucidate the degradation process. First-order kinetics were found for the photolytically induced decomposition of the Si-NH-Si network, the subsequent formation of the methyl-Si-O-Si network and the concomitant degradation of the Si-CH(3) bond, which were additionally independent of the photon energy above a threshold of about 5.5 eV (225 nm). The kinetics of these processes were, however, dependent on the dose actually absorbed by the layer and, in the case of Si-O-Si formation, additionally on the oxygen concentration. The release of ammonia and methane accompanied the conversion process. Quantum-chemical calculations on methyl substituted cyclotetrasilazanes as model compounds substantiate the suggested reaction scheme. Layers <100 nm in thickness based on mixtures of poly(1,1-dimethylsilazane-co-1-methylsilazane) and perhydropolysilazane (PHPS) were coated onto polyethylene terephthalate (PET) foils by a continuous roll to roll process and cured by VUV irradiation by using wavelengths <200 nm and investigated for their O(2) and water vapor-barrier properties. It was found that the resulting layers displayed oxygen and water vapor transmission rates (OTR and WVTR, respectively) of <1 cm(3) m(-2) d(-1) bar(-1) and <4 g m(-2) d(-1), respectively.


Baseline Corrected QT Interval Dispersion Is Useful to Predict Effectiveness of Metoprolol on Pediatric Postural Tachycardia Syndrome.
The study was designed to explore the role of baseline-corrected QT interval dispersion (QTcd) in predicting the effectiveness of metoprolol on pediatric postural tachycardia syndrome (POTS). There were two groups in the study, the discovery group and the validation group. The children with POTS in the discovery group were treated with oral metoprolol, with the completed necessary medical records, head-up tilt test (HUTT), blood chemistry, and 12-lead ECG before treatment at the pediatrics of Peking University First Hospital, China. According to whether the symptom score (SS) was reduced by more than 2 points after administration with oral metoprolol as compared with that before treatment, the children with POTS were separated into responders and non-responders. The demographic characteristics, hemodynamic indicators, and the QTcd of the two groups were compared, and the estimate of the baseline QTcd in predicting the treatment response to metoprolol was tested through a receiver operating characteristic (ROC) analysis. Other 24 children suffering from POTS who were, administrated with metoprolol at the pediatrics of Peking University First Hospital were included in the validation group. The sensitivity, specificity, and accuracy of the baseline QTcd in the prediction of the effectiveness of metoprolol on POTS were validated in children. The pre-treatment baseline QTcd in responders treated with metoprolol was longer than that of the non-responders in the discovery group [(66.3 ± 20.3) ms vs. (45.7 ± 19.9) ms, p = 0.001]. The baseline QTcd was negatively correlated with SS after metoprolol treatment (r = -0.406, p = 0.003). The cut-off value of baseline QTcd for the prediction of the effectiveness of metoprolol on pediatric POTS was 47.9 ms, yielding a sensitivity of 78.9% and a specificity of 83.3%, respectively. The validation group showed that the sensitivity, specificity, and accuracy of the baseline QTcd ≥ 47.9 ms before treatment for estimating the effectiveness of metoprolol on POTS in children were 73.7, 80.0, and 75.0%, respectively. Baseline QTcd is effective for predicting the effectiveness of metoprolol on pediatric POTS.


Drop Jump Asymmetry is Associated with Reduced Sprint and Change-of-Direction Speed Performance in Adult Female Soccer Players.
Studies that examine the effects of inter-limb asymmetry on measures of physical performance are scarce, especially in adult female populations. The aim of the present study was to establish the relationship between inter-limb asymmetry and speed and change-of-direction speed (CODS) in adult female soccer players. Sixteen adult players performed a preseason test battery consisting of unilateral countermovement jump (CMJ), unilateral drop jump (DJ), 10 m, 30 m, and 505 CODS tests. Inter-limb asymmetry was calculated using a standard percentage difference equation for jump and CODS tests, and Pearson's r correlations were used to establish a relationship between asymmetry and physical performance as well as asymmetry scores themselves across tests. Jump-height asymmetry from the CMJ (8.65%) and DJ (9.16%) tests were significantly greater (p < 0.05) than asymmetry during the 505 test (2.39%). CMJ-height asymmetry showed no association with speed or CODS. However, DJ asymmetries were significantly associated with slower 10 m (r = 0.52; p < 0.05), 30 m (r = 0.58; p < 0.05), and 505 (r = 0.52⁻0.66; p < 0.05) performance. No significant relationships were present between asymmetry scores across tests. These findings suggest that the DJ is a useful test for detecting existent between-limb asymmetry that might in turn be detrimental to speed and CODS performance. Furthermore, the lack of relationships present between different asymmetry scores indicates the individual nature of asymmetry and precludes the use of a single test for the assessment of inter-limb differences.


Stereotactic body radiotherapy for unresected pancreatic cancer: A nationwide review.
The role of conventional radiotherapy in the management of pancreatic cancer has yet to be elucidated. Over the past decade, stereotactic body radiotherapy (SBRT) has emerged as a novel therapeutic option in pancreatic cancer care. This study evaluated the survival impact of SBRT on patients with unresected pancreatic cancer. The National Cancer Data Base was queried for unresected patients who received chemotherapy for nonmetastatic pancreatic adenocarcinoma between 2004 and 2012. Four treatment groups were identified: chemotherapy alone, chemotherapy combined with external-beam radiotherapy (EBRT), chemotherapy combined with intensity-modulated radiotherapy (IMRT), and chemotherapy combined with SBRT. Propensity score models predicting the odds of receiving SBRT were created to control for potential selection bias, and patients were matched by propensity scores. The survival analysis was performed with the Kaplan-Meier method. A total of 14,331 patients met the inclusion criteria. Chemotherapy alone was delivered to 5464 patients (38.1%); 6418 (44.8%), 322 (2.3%), and 2127 (14.8%) received chemotherapy along with EBRT, IMRT, and SBRT, respectively. The unadjusted median survival before matching was 9.9, 10.9, 12.0, and 13.9 months for patients treated with chemotherapy, EBRT, IMRT, and SBRT, respectively. In separate matched analyses, SBRT remained superior to chemotherapy alone (log-rank P < .0001) and EBRT (log-rank P = .0180). After matching, survival did not differ between patients receiving IMRT and patients receiving SBRT (log-rank P = .0492). SBRT is associated with a significantly better outcome than chemotherapy alone or in conjunction with traditional EBRT. These results support the idea that SBRT is a promising treatment approach for patients with unresected pancreatic cancer. Cancer 2017;123:4158-4167. © 2017 American Cancer Society.


Vancomycin resistance: structure of D-alanine:D-alanine ligase at 2.3 A resolution.
The molecular structure of the D-alanine:D-alanine ligase of the ddlB gene of Escherichia coli, co-crystallized with an S,R-methylphosphinate and adenosine triphosphate, was determined by x-ray diffraction to a resolution of 2.3 angstroms. A catalytic mechanism for the ligation of two D-alanine substrates is proposed in which a helix dipole and a hydrogen-bonded triad of tyrosine, serine, and glutamic acid assist binding and deprotonation steps. From sequence comparison, it is proposed that a different triad exists in a recently discovered D-alanine:D-lactate ligase (VanA) present in vancomycin-resistant enterococci. A molecular mechanism for the altered specificity of VanA is suggested.


Prevention of DSS-induced colitis in mice with water kefir microbiota via anti-inflammatory and microbiota-balancing activity.
Water kefir, a natural and stable functional microbiota system consisting of a symbiotic mixture of probiotics, shows multiple bioactivities but little is known about the effect of water kefir microbiota on the prevention of inflammatory bowel disease (IBD), which is one of the most common intestinal problems and has become a worldwide public health concern. Here, the main objectives of the present study were to investigate the preventative effects of water kefir microbiota, a probiotic consortium mainly consisting of bacteria belonging to Acetobacter, Lactobacillus, and Komagataeibacter and fungi belonging to Saccharomyces and Talaromyces, in a dextran sodium sulfate (DSS)-induced colitis mouse model and unveil the underlying mechanism of the action. Water kefir microbiota effectively improved the disease severity of DSS-induced colitis, including decreased body weight and colon length, increased spleen index and DAI score, and colonic tissue damage. Moreover, water kefir microbiota restored the abnormal expression of tight junction proteins (such as occludin, ZO-1, and claudin-1) and pro-inflammatory and anti-inflammatory cytokines (such as IL-1β, IL-6, TNF-α, COX-2, iNOS, and IL-10) and inactivated TLR4-MyD88-NF-κB pathway induced by DSS. Water kefir microbiota also improved the composition and metabolism of intestinal microbiota. These findings demonstrated that water kefir microbiota could exert protective roles in the DSS-induced colitis mouse model by reducing inflammation and regulating microbial dysbiosis, which will be helpful for the development of water kefir microbiota-based microbial products as an alternative preventative strategy for IBD.


Munc-18-2 regulates exocytosis of H(+)-ATPase in rat inner medullary collecting duct cells.
Exocytic insertion of H(+)-ATPase into the apical membrane of inner medullary collecting duct (IMCD) cells is dependent on a soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein target receptor (SNARE) complex. In this study we determined the role of Munc-18 in regulation of IMCD cell exocytosis of H(+)-ATPase. We compared the effect of acute cell acidification (the stimulus for IMCD exocytosis) on the interaction of syntaxin 1A with Munc-18-2 and the 31-kDa subunit of H(+)-ATPase. Immunoprecipitation revealed that cell acidification decreased green fluorescent protein (GFP)-syntaxin 1A and Munc-18-2 interaction by 49 +/- 7% and increased the interaction between GFP-syntaxin 1A and H(+)-ATPase by 170 +/- 23%. Apical membrane Munc-18-2 decreased by 27.5 +/- 4.6% and H(+)-ATPase increased by 246 +/- 22%, whereas GP-135, an apical membrane marker, did not increase. Pretreatment of IMCD cells with a PKC inhibitor (GO-6983) diminished the previously described changes in Munc-18-2-syntaxin 1A interaction and redistribution of H(+)-ATPase. In a pull-down assay of H(+)-ATPase by glutathione S-transferase (GST)-syntaxin 1A bound to beads, preincubation of beads with an approximately twofold excess of His-Munc-18-2 decreased H(+)-ATPase pulled down by 64 +/- 16%. IMCD cells that overexpress Munc-18-2 had a reduced rate of proton transport compared with control cells. We conclude that Munc-18-2 must dissociate from the syntaxin 1A protein for the exocytosis of H(+)-ATPase to occur. This dissociation leads to a conformational change in syntaxin 1A, allowing it to interact with H(+)-ATPase, synaptosome-associated protein (SNAP)-23, and vesicle-associated membrane protein (VAMP), forming the SNARE complex that leads to the docking and fusion of H(+)-ATPase vesicles.


Clostridium perfringens Septicemia and a Bleeding Ulcer of a Jejunal Interposition: A Case Report and Short Review of the Literature.
We report a case of Clostridium perfringens septicemia in a patient presenting with a bleeding ulcer of a jejunal interposition. An 81-year-old female patient was acutely admitted to our hospital due to hematemesis and melena. She had a history of metastatic gastrointestinal stromal tumor, for which she was receiving second line treatment with sunitinib. She had also undergone a Merendino procedure 4 years prior to presentation. The patient underwent emergency gastroscopy, which revealed a bleeding ulcer in the jejunal interposition. Despite initial endoscopic control of the bleeding and transfusion of blood products, the hemoglobin level continued to drop, and the patient was treated for an assumed hemolytic transfusion reaction. The patient died 3 days following admission, and the results of blood cultures later confirmed a Clostridium perfringens septicemia. The postmortem examination revealed a diffuse spread of Clostridium perfringens to multiple organs. This case is a reminder of the importance of considering septicemia, particularly in association with Clostridium perfringens, as a potential cause of hemolysis. It also demonstrates the extent of organ involvement in a case of diffuse clostridial myonecrosis.


Legislative perspectives on diabetes in America.
To highlight the ongoing legislative activity in support of diabetes management. Efforts of the Senate Diabetes Caucus have been instrumental in increasing the budget of the National Institutes of Health from $13.6 billion to $20.4 billion during the past 3 years, including more than doubling of the funding for diabetes research (from $319 million to $690 million). The demonstrated effectiveness of the Diabetes Prevention Program in delaying or preventing the development of type 2 diabetes by use of diet and exercise or metformin emphasizes the importance of diabetes educational programs for high-risk persons. Government funding of diabetes educational and research programs improves the quality of life for patients with diabetes and ultimately saves money.


Balancing Prolonged Survival with QoL Using Low-dose Pazopanib Maintenance: A Comparison with the PALETTE Study.
A consensus has not been reached regarding the optimal pazopanib dosing schedule, which we determined in patients who received pazopanib at our Institution. Twenty-five patients who were prescribed pazopanib between 2012 and 2015 were included in this retrospective analysis. The median progression-free survival (PFS) time was 7.7 months. This time (various doses) was similar to that achieved by high-dose pazopanib in the PALETTE study. The log-rank test revealed no significant differences in the PFS times between the low- and high-dose pazopanib groups, with the majority of patients receiving a dose of 400 mg, indicating that controlling the side-effects might be more critical than administering higher doses. Pazopanib should be started from a low dose with careful increase to avoid pazopanib-related side-effects, which is necessary to provide a balance between the life-prolonging effects of pazopanib and quality of life (QoL) of patients.


Incorporation of the Arc1p tRNA-binding domain to the catalytic core of MetRS can functionally replace the yeast Arc1p-MetRS complex.
The catalytic core of methionyl-tRNA synthetase (MetRS) is conserved among all life kingdoms but, depending on species origin, is often linked to non-catalytic domains appended to its N- or C-terminus. These domains usually contribute to protein-protein or protein-tRNA interactions but their exact biological role and evolutionary purpose is poorly understood. Yeast MetRS contains an N-terminal appendix that mediates its interaction with the N-terminal part of Arc1p. Association with Arc1p controls the subcellular distribution of MetRS. Furthermore, the C-terminal part of Arc1p harbors a conserved tRNA-binding domain (TRBD) required for the Arc1p-dependent stimulation of the catalytic activity of MetRS. The same TRBD is found directly fused to catalytic domains of plant and nematode MetRS as well as human tyrosyl-tRNA synthetase. To investigate the purpose of Arc1p-MetRS complex formation in yeast, we tested the ability of TRBD to assist the function of MetRS independently of Arc1p. We attached the TRBD directly to the C-terminus of the MetRS catalytic core (MC) by constructing the chimeric protein MC-TRBD. The effect of MC-TRBD expression on yeast cell growth as well as its localization and in vitro aminoacylation activity were analyzed and compared to that of MC alone or wild-type MetRS, both in the absence or presence of Arc1p. We show that MC-TRBD exhibits improved enzymatic activity and can effectively substitute the MetRS-Arc1p binary complex in vivo. Moreover, MC-TRBD, being exclusively cytoplasmic, also mimics the MetRS-Arc1p complex in terms of subcellular localization. Our results suggest that the sole role of the N-terminal appended domain of yeast MetRS is to mediate the indirect association with the TRBD, which, nevertheless, can also function effectively in vivo when directly fused to the catalytic MetRS core.


B(C6F5)3-mediated transformations and hydrogenation of carbodiimides.
The reactivity of a series of carbodiimides RNCNR (R=tBu (1 a), iPr (1 b), SiMe3 (1 c), and Dipp (2,6-di-iso-propylphenyl (1 d)) with B(C6 F5 )3 was investigated. After initial adduct formation, several distinct reaction pathways were identified. These pathways involve either isomerization of the carbodiimide to cyanamide derivatives or insertion of a carbodiimide into a BC bond of B(C6 F5 )3 to yield four-membered heterocycles. In the presence of dihydrogen, stepwise hydrogenation of the heteroallene moiety in the carbodiimides was achieved, which yielded the respective amidine-B(C6 F5 )3 adducts and amidinium borate salts upon reaction with one or two equivalents of H2 , respectively.


Entry of cell-penetrating peptide transportan 10 into a single vesicle by translocating across lipid membrane and its induced pores.
The cell-penetrating peptide, transportan 10 (TP10), can translocate across the plasma membrane of living cells and thus can be used for the intracellular delivery of biological cargo such as proteins. However, the mechanisms underlying its translocation and the delivery of large cargo remain unclear. In this report we investigated the entry of TP10 into a single giant unilamellar vesicle (GUV) and the TP10-induced leakage of fluorescent probes using the single GUV method. GUVs of 20% dioleoylphosphatidylglycerol (DOPG)/80% dioleoylphosphatidylcholine (DOPC) were prepared, and they contained a water-soluble fluorescent dye, Alexa Fluor 647 hydrazide (AF647), and smaller vesicles composed of 20% DOPG/80% DOPC. The interaction of carboxyfluorescein (CF)-labeled TP10 (CF-TP10) with these loaded GUVs was investigated using confocal microscopy. The fluorescence intensity of the GUV membrane increased with time to a saturated value, then the fluorescence intensity due to the membranes of the smaller vesicles inside the GUV increased prior to leakage of AF647. This result indicates that CF-TP10 entered the GUV from the outside by translocating across the lipid membrane before CF-TP10-induced pore formation. The rate constant of TP10-induced pore formation in lipid membranes increased with an increase in TP10 concentration. Large molecules such as Texas Red Dextran 40,000, and vesicles with a diameter of 1-2 μm, permeated through the TP10-induced pores or local rupture in the lipid membrane. These results provide the first direct experimental evidence that TP10 can deliver large cargo through lipid membranes, without the need for special transport mechanisms such as those found in cells.


Functional reconstitution of the solubilized Arabidopsis thaliana STP1 monosaccharide-H+ symporter in lipid vesicles and purification of the histidine tagged protein from transgenic Saccharomyces cerevisiae.
Complete DNA sequences encoding the Arabidopsis thaliana STP1 monosaccharide/H+ symporter or a histidine-tagged STP1-His6 protein were expressed in baker's yeast Saccharomyces cerevisiae. Both wild-type STP1 and the recombinant his-tagged protein were located in the plasma membranes of transformed yeast cells. The C-terminal modification caused no loss of transport activity compared with the wild-type protein. Anti-STP1-antibodies were used to confirm the identity of the protein in yeast and to compare the apparent molecular weights of STP1 proteins in membrane extracts from yeast or Arabidopsis thaliana. Purified yeast plasma membranes were fused with proteoliposomes consisting of Escherichia coli lipids and beef heart cytochrome-c oxidase. Addition of ascorbate/TMPD/cytochrome-c to these fused vesicles caused an immediate formation of membrane potential (inside negative; monitored with [3H]tetraphenylphosphonium cations) and a simultaneous, uncoupler-sensitive influx of D-glucose into the energized vesicles. STP1-His6 protein is functionally active after solubilization with octyl-beta-D-glucoside, which was shown by insertion of the protein into proteoliposomes by detergent dilution and determination of the resulting transport capacity. Detergent extracts from either total membranes or plasma membranes of transgenic yeast cells were used for one-step purification of the STP1-His6 protein on Ni(2+)-NTA columns. The identity of the purified protein was checked by immunoblotting and N-terminal sequencing.


The role of robustness and changeability on the origin and evolution of genetic codes.
We propose that an essential factor on the origin of genetic codes is a balanced accomplishment of robustness and changeability, two antithetical, but fundamental, properties for the survival and evolution of organisms. These measures are defined as the intrinsic properties of genetic codes. An evaluation of these properties explains the structural regularity of genetic codes, estimates the order of codon reassignment in deviant codes, and predicts the most probable deviant codes that exist. The enumeration of genetic codes that could have evolved from the standard genetic code under the selection pressure on robustness and changeability strongly limits the freedom of codon reassignments. The codon reassignments of all currently known deviant genetic codes belong to this predicted evolutionary path, and they generally give the highest improvements on robustness and changeability.


[Use of a new ultra short-acting beta adrenoblocker esmolol in anesthesiological practice].
The effect of a novel ultrashort acting beta-adrenoblocker esmolol on systemic and pulmonary hemodynamics has been studied intraoperatively in 81 cardiosurgical patients. All the patients were operated under ataralgesia. Esmolol is an effective controlled agent for the treatment and prevention of supraventricular tachycardia and hyperdynamic reaction developing in cardiothoracic patients during anesthesia and surgery. Bolus injection of 100 mg esmolol exerts a negative chronotropic effect with maximum heart rate decrease by 23.3% by minute 5 and a gradual attenuation of the effect by minute 20. A parallel drop in the cardiac output by 18.5% is caused predominantly by a decrease in the heart rate and accounts for BP reduction. The above esmolol dose does not have a considerable effect on pulmonary hemodynamics and does not enhance intrapulmonary venous shunting.


[Conclusion: Learning to live together again].
In the face of increasing individualism, the social links which hold our society together could eventually disintegrate. Specific case studies of the summer 2003 heat wave, as well as mental illnesses, addictions, Alzheimer's disease, prisoners and migrants can offer solutions to help tackle solitude. Voluntary associations can play a key role.


Influence of high temperature stress of 16-day embryos on subsequent hatchability.
Two experiments were conducted to determine the effect of acute heat stress on late-stage chicken embryos. Embryos were incubated at a normal control temperature (37.5 degrees C.) for 16 days and were then subjected to 40.6, 43.3, 46.1 or 48.9 degrees C. for various periods of time in another incubator of the same type. At the end of the stress period all embryos were placed back into the control incubator for the remainder of the incubation period. Exposure of embryos for 24 hours to a temperature of 40.6 degrees C, caused no major detrimental effects on hatchability. Exposure for 6 hours to the temperature of 43.3 degrees C, caused a decrease in hatchability with a severe decline in hatchability occurring after 9 hours of exposure. Exposure to 46.1 degrees C. for 3 hours or 48.9 degrees C for 1 hour killed all embryos. Chicks which hatched following a severe heat stress had a high incidence of clubbed, wiry down and exhibited an unsteady gait.


Development of a real-time PCR for detection of the oyster pathogen Nocardia crassostreae based on its homogeneous 16S-23S rRNA intergenic spacer region.
Nocardia crassostreae, the causative agent of Pacific oyster nocardiosis (PON), is a Gram-positive actinomycete bacterium associated with Pacific oyster (Crassostrea gigas) mortalities. Oysters infected with this bacterium have been reported previously from the west coast of North America and Japan. More recently, N. crassostreae was reported in oyster culture areas in the Netherlands. In this study, a sensitive real-time PCR for specific detection of N. crassostreae was developed, and the intra-species divergence of N. crassostreae from different geographical locations was studied. The 16S-23S rRNA intergenic spacer (ITS) region of N. crassostreae was sequenced for a number of infected oysters originating from the Netherlands, Japan and Canada. The sequence analyses showed an absence of genetic variation in the ITS region between N. crassostreae from different geographical locations. Based on these ITS sequences a species-specific and highly sensitive SYBR Green real-time PCR assay was developed to facilitate detection of N. crassostreae in oyster tissue. To evaluate this new detection tool for N. crassostreae a preliminary validation was carried out and real-time PCR results were compared with other detection methods (histology, conventional PCR and bacterial isolation) using field samples from Lake Grevelingen, the Netherlands. The genetic homogeneity in the ITS region between N. crassostreae from different geographical locations might be explained by the recent spread of the organism via the international trade in Pacific oysters for aquaculture purposes. However, the lack of genetic variation could also suggest that N. crassostreae is a genetically monomorphic species.


Novel equations for estimating intraperitoneal pressure among peritoneal dialysis patients.
Increased intraperitoneal pressure (IPP) is associated with abdominal wall complications and technical failure in peritoneal dialysis (PD). Since the standard measurement of IPP is limited due to its cumbersome procedures, we aimed to develop and validate equations for estimating IPP. We performed a cross-sectional study with a total of 200 prevalent PD patients who were divided into development and validation datasets after random sampling matched by body mass index. The IPPs were measured using the Durand method, with whole-body and abdominal anthropometry indices collected. Equations with 2.0-L and 1.5-L fill volumes were generated by stepwise linear regression modelling. The bias, accuracy and precision of the estimated IPP (eIPP) with 2-L and 1.5-L fill volumes were compared with actual IPPs by the Durand method. The eIPP for the 2-L fill volume was also compared with other existing equations. Two new equations incorporating waist circumference and height from the decubitus plane to mid-axillary line were generated. The eIPPs exhibited small biases in relation to the Durand method , with median differences of -0.24 cmH2O and -0.10 cmH2O for 2 L and 1.5 L, respectively. The precisions evaluated by the standard deviation of the absolute value of the differences were 2.59 cmH2O and 2.50 cmH2O, respectively. The accuracies evaluated by the value of the percentage of estimates that differed by >20% for the eIPP were 26% for 2.0 L and 27% for 1.5 L. Better bias, precision and accuracy were observed for the eIPP equation compared with other existing equations for the 2.0-L fill volume. We provided two new equations developed from abdominal anthropometry indices to accurately estimate the IPP in the PD population.


Genetic variation in major histocompatibility complex class I alpha2 gene among broilers divergently selected for high or low early antibody response to Escherichia coli.
The MHC genes have a profound effect on animal abilities to respond to specific antigens because they play a role in presenting foreign antigens to T cells during the course of the humoral or cellular immune response. In the current study, polymorphism in the MHC class I alpha2 domain was compared in 2 lines divergently selected for high (HH) or low (LL) antibody response to Escherichia coli vaccine. These lines also differ markedly in their antibody response to natural E. coli exposure and to vaccination with Newcastle disease virus, infectious bronchitis virus, and infectious bursa disease virus. Recent trials have shown that the LL chicks exhibit a significantly higher percentage of CD8+ T lymphocytes in their peripheral blood lymphocytes and spleen than HH chicks. Despite symmetrical selection intensity in both lines, polymorphism of the alpha2-domain gene was higher in the LL line than in the HH line. Among 29 single-nucleotide polymorphism positions found, 3 were unique to the HH line, 15 were unique to the LL line, and 11 were polymorphic in both lines. These single nucleotide polymorphism positions were not 100% line specific and were in agreement with the genetic variation in antibody level or cellular response still found within the selection lines. Five amino acid positions showed significant differences in polymorphism between the selection lines. These were located within the antigen-binding cleft, suggesting that these positions might influence the ability of MHC class I to bind foreign antigens and leading to differences in immunocompetence between the lines.


Coronavirus as a Trigger Of Graves' Disease.
SARS-CoV-2 infection was declared a pandemic in 2020 and affected millions of people worldwide. Angiotensin-converting enzyme-2 receptors, through which coronavirus enters the cells of different organs, have been detected in the thyroid gland. The most common cause of thyrotoxicosis is Graves' disease in which thyroid-receptors antibodies (TRAb) stimulate the TSH receptor, increasing thyroid hormone production and release. A 22-year-old woman had symptoms of palpitation, tremor, muscle weakness, anxiety and sleep disturbance. 3 weeks before the onset of these symptoms, the patient suffered from COVID-19, which lasted 14 days and was characterized by a course of moderate severity with fever up to 38°C, general weakness without shortness of breath. The patient had no pre-existing thyroid problems. Her TSH was <0.01 mU/L, FT4, FT3 and TRAb were increased. Antithyroid drugs, glucocorticosteroids and β-blockers were prescribed. During 3 months of treatment doses of methimazole, methylprednisolone and bisoprolol were gradually reduced due to the improvement of the patient's condition and thyroid tests normalization. COVID-19 infection can cause Graves' disease and thyrotoxicosis. The onset of this disease after SARS-CoV-2 does not depend on the presence of pre-existing thyroid pathology and requires the appointment of glucocortisteroids.


Treatment of Renal Angiomyolipoma and Other Hamartomas in Patients with Tuberous Sclerosis Complex.
Tuberous sclerosis complex is an autosomal dominant genetic disease characterized by growth of benign tumors (hamartomas) in multiple organs, especially the kidneys, brain, heart, lungs, and skin. Tuberous sclerosis complex is usually caused by a mutation in either the tuberous sclerosis complex 1 or tuberous sclerosis complex 2 gene, resulting in constitutive activation of mammalian target of rapamycin signaling. Currently, mammalian target of rapamycin inhibitors are recommended in adult patients with tuberous sclerosis complex for the treatment of asymptomatic, growing renal angiomyolipoma that are >3 cm in diameter and pediatric or adult patients with brain lesions (subependymal giant cell astrocytoma) that either are growing or are not amenable to surgical resection. Clinical evidence suggests that systemic administration of a mammalian target of rapamycin inhibitor may provide concurrent improvements in multiple lesions and symptoms of tuberous sclerosis complex. With the major paradigm shift in consensus guidelines toward screening at diagnosis and ongoing monitoring and with the recent availability of an effective oral treatment, it is important that nephrologists have a thorough understanding of our role in the management of patients with tuberous sclerosis complex. Because the various manifestations of tuberous sclerosis complex typically emerge at different periods during patients' lifetimes, patients will need to be followed throughout their lives. Unlike brain and cardiac lesions, renal lesions are more likely to emerge as patients age and can grow at any time. Considerations regarding long-term medication administration for the potential control of multiple tuberous sclerosis complex manifestations will need to be addressed; these include the most appropriate starting dose, appropriate doses for tumor shrinkage versus prevention of regrowth, and management of adverse events. Best practices and potential obstacles for nephrologists treating patients with tuberous sclerosis complex who have multiple manifestations are considered.


On the mechanisms of cardiac electrophysiologic actions of adenosine and adenosine 5'-triphosphate.
Adenosine and ATP exert pronounced electrophysiologic actions on the mammalian heart including a negative chronotropic action on cardiac pacemakers and a negative dromotropic action on atrioventricular conduction. These actions are modulated by complex interactions of the two compounds with the autonomic nervous system. Since both adenosine and ATP are released from myocardial cells under physiologic and pathophysiologic conditions, they could play an important modulating role in cardiac electrophysiology. Indeed, studies during the last decade have yielded strong evidence for the role of adenosine in the genesis of specific arrhythmias associated with myocardial ischemia. Further studies are required to fully elucidate the mechanisms of actions of adenosine and ATP in vivo. These will undoubtedly enhance the understanding of the potential arrhythmogenic, as well as the antiarrhythmic actions of endogenous and exogenous adenosine and ATP.


Sodium-Glucose Cotransporter-2 (SGLT-2) Attenuates Serum Uric Acid (SUA) Level in Patients with Type 2 Diabetes.
Hyperuricemia has a strong association with diabetes mellitus. Hyperuricemia can lead to cardiovascular and renal complications in patients with diabetes. The goal of this study was to compare the effect of sodium-glucose cotransporter-2 (SGLT-2) inhibitors dapagliflozin and empagliflozin on serum uric acid (SUA) levels in patients with type 2 diabetes against traditional oral antihyperglycemic drugs (OADs). In this double-blind randomized controlled trial, 70 patients with type 2 diabetes and elevated SUA levels were assigned to two treatment groups. Patients in group A received SGLT-2 inhibitors tablet dapagliflozin 5 mg to 10 mg and empagliflozin 10 mg to 25 mg. Group B patients received OADs such as glimepiride, metformin, sitagliptin, gliclazide, and glibenclamide as monotherapy or combination therapy. The changes in SUA level were primary end points while changes in body weight and body mass index (BMI) from baseline to end point were secondary end points. After four weeks of treatment, we noted a significant reduction of mean SUA levels in the SGLT-2 inhibitor group from 7.5 ± 2.5 to 6.3 ± 0.8 mg/dl versus comparator group from 7.1 ± 1.8 to 6.8 ± 2.2 mg/dl (p = 0.001). Mean body weight was significantly reduced in the SGLT-2 group from 82 ± 10.4 to 78 ± 12.5 kg versus comparator group from 78 ± 13.2 to 79.2 ± 9.7 kg (p = 0.001). Similarly, the mean BMI of patients in the SGLT-2 group was significantly reduced from 25.7 ± 3.2 to 24.2 ± 3.2 kg/m2 versus comparator group from 27.5 ± 4.2 to 28 ± 3.6 kg/m2 (p = 0.002). SGLT-2 inhibitors have a strong potential to decrease SUA levels in patients with type 2 diabetes.


Enhanced cerebro-cerebellar functional connectivity reverses cognitive impairment following electroconvulsive therapy in major depressive disorder.
Electroconvulsive therapy (ECT), a rapidly acting and effective treatment for major depressive disorder (MDD), is frequently accompanied by cognitive impairment. Recent studies have documented that ECT reorganizes dysregulated inter/intra- connected cerebral networks, including the affective network, the cognitive control network(CCN) and default mode network (DMN).Moreover, cerebellum is thought to play an important role in emotion regulation and cognitive processing. However, little is known about the relationship between cerebro-cerebellar connectivity alterations following ECT and antidepressant effects or cognitive impairment. We performed seed-based resting-state functional connectivity (RSFC) analyses in 28 MDD patients receiving ECT and 20 healthy controls to identify cerebro-cerebellar connectivity differences related to MDD and changes induced by ECT. Six seed regions (three per hemisphere) in the cerebrum were selected for RSFC, corresponding to the affective network, CCN and DMN, to establish cerebro-cerebellar functional connectivity with cerebellum. MDD patients showed increased RSFC between left sgACC and left cerebellar lobule VI after ECT. Ggranger causality analyses (GCA) identified the causal interaction is from left cerebellar lobule VI to left sgACC. Furthermore, increased effective connectivity from left cerebellar lobule VI to left sgACC exhibited positively correlated with the change in verbal fluency test (VFT) score following ECT (r = 0.433, p = 0.039). Our findings indicate that the enhanced cerebro-cerebellar functional connectivity from left lobule VI to left sgACC may ameliorate cognitive impairment induced by ECT. This study identifies a potential neural pathway for mitigation of cognitive impairment following ECT.


"I've never been able to stay in a job": A qualitative study of Veterans' experiences of maintaining employment.
Ensuring Veteran employment needs are met is a top priority for the Department of Veteran Affairs and the United States government. However, Veterans, especially those with mental health disorders, continue to encounter difficulties when employed. While many employment related programs offer numerous services aimed at helping Veterans gain employment, their ability to maintain long-term employment remains unknown. The objective of this study was to understand factors that affect the ability of Veterans with mental health disorders to maintain long-term employment. An exploratory, qualitative study design consisting of semi-structured interviews with 10 Veterans was performed. Inductive thematic analysis was performed to identify salient themes. We found that participants' symptoms manifested themselves within the workplace affecting their ability to maintain employment, participants felt as if they had been demoted from what they did in the military, and they felt unable to relate to civilian co-workers. Strategies that helped some transition into the civilian workforce were also identified. A better understanding of the difficulties some Veterans face when trying to maintain employment is needed. Our findings suggest that increasing awareness of existing programs and ensuring that services provide resources and skills that help Veterans maintain long-term employment is critical.


Sleep and metabolic control: waking to a problem?
1. The aim of the present review is to outline: (i) the association between sleep and metabolism; (ii) how sleep duration influences the development of disease; and (iii) how sex differences, ageing and obesity may potentially influence the relationship between sleep, metabolic control and subsequent disease. 2. Sleep is associated with a number of endocrine changes, including a change in insulin action in healthy young individuals. Sleep duration shows a prospective U-shaped relationship with all-cause mortality, cardiovascular disease and Type 2 diabetes. 3. Chronic sleep restriction is becoming more common. Experimental sleep restriction impedes daytime glucose control and increases appetite. 4. The sex hormones oestrogen and testosterone influence sleep duration and quality and may account for sex differences in the prevalence of sleep-related disorders. 5. Ageing is associated with a decreased sleep duration, decreased muscle mass and impaired insulin action. 6. Obesity impairs insulin action and is associated with the incidence and severity of obstructive sleep apnoea. 7. Sleep plays an integral role in metabolic control. Consequently, insufficient sleep may represent a modifiable risk factor for the development of Type 2 diabetes. The challenge ahead is to identify how sex differences, ageing and obesity could potentially influence the relationship between sleep and metabolism.


The end of fertility: age, fecundity and fecundability in women.
Onset of capacity for childbearing in women is dated biologically by menarche, although actual onset may be delayed. The end of childbearing is less understood but recent demographic and biological research on fertility at older ages in clarifying the end of fertility. The demographic view of declining fertility with age is based on age-specific fertility in natural fertility populations, artificial insemination and pregnancy rates by age and World Fertility Survey data. New data from the Demographic and Health Surveys on exposure to the risk of pregnancy shows that whereas older women biologically need longer exposure to pregnancy, exposure declines on behavioural grounds such as duration of marriage. Actual fecundity is obscured by factors of fecundability. Recent research on medically assisted conception is adding to the understanding of declining fecundity with age, especially the relative contributions of endometrial and ovarian ageing. This paper reviews the available information on declining fertility with age and discusses the implications of the extension of fertility through new medical technologies.


Frontline clinical diagnosis-FTIR on pancreatic cancer.
Accurate, easily accessible and economically viable cancer diagnostic tools are pivotal in improving the abysmal 5% survival rate of pancreatic cancer. A novel, affordable, non-invasive diagnostic method has been developed by combining measurement precision of infrared spectroscopy with classification using machine learning tools. Diagnosis accuracy as high as 90% has been achieved. The study investigated urine and blood from pancreas cancer patients and healthy volunteers, and significantly improved accuracy by focusing on sweet-spots within blood plasma fractions containing molecules within a narrow range of molecular weights.


[Experience of using a triple fixed combination in the treatment of patients with chronic obstructive pulmonary disease].
To evaluate the effectiveness of a fixed triple combination of vilanterol/umeclidinium bromide/fluticasone furoate in the treatment of chronic obstructive pulmonary disease (COPD) patients with frequent exacerbations. The study included 46 patients with severe and extremely severe COPD (GOLD 34) with frequent exacerbations. All patients were divided into 2 groups. The 1st group included 22 COPD patients with a content of eosinophils in the peripheral blood of 300 cells/ml, the 2nd group included 24 COPD patients with no signs of eosinophilic inflammation in the peripheral blood. Group 1 patients were recommended therapy with a fixed triple combination of vilanterol/umeclidinium bromide/fluticasone furoate at a dose of 22/55/92 mcg 1 time per day, group 2 patients received vilanterol+umeclidinium bromide at a dose of 22/55 mcg 1 time per day. The duration of follow-up was 12 months. After 12 months of treatment with a fixed triple combination of vilanterol/umeclidinium bromide/fluticasone furoate, a statistically significant decrease in peripheral blood eosinophilia was noted in patients with COPD with frequent exacerbations and peripheral blood eosinophilia (p=0.001), as well as a decrease in shortness of breath on the MMRs scale (p=0.001) and the frequency of exacerbations in patients with COPD with frequent exacerbations and eosinophilia (p=0.001). The use of a fixed combination of vilanterol/umeclidinium bromide/fluticasone furoate for 12 months allowed to reduce the impact of the disease, improve respiratory function and quality of life in COPD patients with eosinophilia.


Mechanisms of hormesis through mild heat stress on human cells.
In a series of experimental studies, it was shown that repetitive mild heat stress has antiaging hormetic effects on growth and various other cellular and biochemical characteristics of human skin fibroblasts undergoing aging in vitro. We have reported the hormetic effects of repeated challenge at the levels of maintenance of stress protein profile; reduction in the accumulation of oxidatively and glycoxidatively damaged proteins; stimulation of the proteasomal activities for the degradation of abnormal proteins; improved cellular resistance to ethanol, hydrogen peroxide, and ultraviolet-B rays; and enhanced levels of various antioxidant enzymes. Detailed analysis of the signal transduction pathways to determine alterations in the phosphorylation and dephosphorylation states of ERK, JNK, and p38 MAP kinases as a measure of cellular responsiveness to mild and severe heat stress is in progress. Furthermore, comparative studies using nonaging immortal cell lines, such as SV40-transformed human fibroblasts, spontaneous osteosarcoma cells, and telomerase-immortalized human bone marrow cells are also in progress for establishing differences in normal and cancerous cells for their responsiveness to mild and severe stresses.


A new qualitative interleukin-6 bedside test can predict pneumonia in patients with severe head injury--comparison to the standard Immulite test and a semiquantitative bedside test.
Severe head injury (SHI) leads to systemic immunosuppression, which is processed by central mechanisms and is associated with a high risk of pneumonia. The timely identification of an immunodepressed condition in SHI patients might help prevent infections by changing the intensive care strategy. The aim of this prospective study is to evaluate a new method for identifying immunodepression and predicting pneumonia. We correlated interleukin (IL)-6 levels determined by the standard test (Immulite) and performed by specialized laboratories with those obtained using the new bedside test (PicoScan) with the occurrence of pneumonia in patients with SHI. Thirty-two patients with isolated SHI were investigated. Analyses were performed on serum samples taken 2 to 24 hours after trauma. Pearson correlation coefficient was 0.924 (P<0.001) for IL-6 values determined by PicoScan versus Immulite and Spearman rho was 0.572 for visual interpretation versus Immulite (P=0.01). Immulite and PicoScan have a positive predictive value of 91% and 100%, respectively, and a negative predictive value of 76% and 86%. The present study investigated for the first time the determination of IL-6 concentrations by PicoScan in patients. Our findings show a good correlation with the results of the standard Immulite test and suggest that the PicoScan may be used as a handy tool to predict pneumonia in SHI patients.


Clinical characteristics, drug resistance, and treatment outcomes among tuberculosis patients with diabetes in Peru.
Diabetes is a risk factor for active tuberculosis (TB). Data are limited regarding the association between diabetes and TB drug resistance and treatment outcomes. We examined characteristics of TB patients with and without diabetes in a Peruvian cohort at high risk for drug-resistant TB. Among TB patients with diabetes (TB-DM), we studied the association between diabetes clinical/management characteristics and TB drug resistance and treatment outcomes. During 2005-2008, adults with suspected TB with respiratory symptoms in Lima, Peru, who received rapid drug susceptibility testing (DST), were prospectively enrolled and followed during treatment. Bivariate and Kaplan-Meier analyses were used to examine the relationships of diabetes characteristics with drug-resistant TB and TB outcomes. Of 1671 adult TB patients enrolled, 186 (11.1%) had diabetes. TB-DM patients were significantly more likely than TB patients without diabetes to be older, have had no previous TB treatment, and to have a body mass index (BMI) >18.5 kg/m(2) (p<0.05). In patients without and with previous TB treatment, the prevalence of multidrug-resistant TB was 23% and 26%, respectively, among patients without diabetes, and 12% and 28%, respectively, among TB-DM patients. Among 149 TB-DM patients with DST results, 104 (69.8%) had drug-susceptible TB and 45 (30.2%) had drug-resistant TB, of whom 29 had multidrug-resistant TB. There was no association between diabetes characteristics and drug-resistant TB. Of 136 TB-DM patients with outcome information, 107 (78.7%) had a favorable TB outcome; active diabetes management was associated with a favorable outcome. Diabetes was common in a cohort of TB patients at high risk for drug-resistant TB. Despite prevalent multidrug-resistant TB among TB-DM patients, the majority had a favorable TB treatment outcome.


Adult perithyroid and cervical thymus-parathyroid unit: case reports of a rare entity.
The thymus-parathyroid unit (TPU) occurring in adults is rare.The main symptoms and important clinical findings are as follows: 2 patients presented with neomercazole-resistant Basedow-Graves disease. A third patient presented with thyroid nodules and a fourth patient with a neck mass after thyroid resection for medullary thyroid carcinoma.The main diagnoses were those of thyroid nodules (either in the context of goiter, or not). In the fourth case the diagnosis was of thyroid medullary carcinoma recurrence in the neck. Thyroidectomy was performed in the 2 cases of Basedow-Graves disease and in the third case (wherein selective neck dissection was also performed). In the fourth case, a neck dissection was performed for a possible medullary carcinoma recurrence. A TPU was microscopically detected in 2 cases with perithyroid location, on thyroidectomies for Basedow-Graves disease and in the 2 other cases with neck soft tissue location (associated with thyroid papillary carcinoma and thyroid medullary carcinoma extension). Postsurgical hypocalcemia requiring treatment occurred in both patients with Basedow-Graves disease and in the fourth patient. The presence of TPU should be acknowledged because such lesions can be misdiagnosed as suspect lymph nodes during thyroid surgery for malignant tumors.


Dynorphin/kappa opioid receptor system regulation on amygdaloid circuitry: Implications for neuropsychiatric disorders.
Amygdaloid circuits are involved in a variety of emotional and motivation-related behaviors and are impacted by stress. The amygdala expresses several neuromodulatory systems, including opioid peptides and their receptors. The Dynorphin (Dyn)/kappa opioid receptor (KOR) system has been implicated in the processing of emotional and stress-related information and is expressed in brain areas involved in stress and motivation. Dysregulation of the Dyn/KOR system has also been implicated in various neuropsychiatric disorders. However, there is limited information about the role of the Dyn/KOR system in regulating amygdala circuitry. Here, we review the literature on the (1) basic anatomy of the amygdala, (2) functional regulation of synaptic transmission by the Dyn/KOR system, (3) anatomical architecture and function of the Dyn/KOR system in the amygdala, (4) regulation of amygdala-dependent behaviors by the Dyn/KOR system, and (5) future directions for the field. Future work investigating how the Dyn/KOR system shapes a wide range of amygdala-related behaviors will be required to increase our understanding of underlying circuitry modulation by the Dyn/KOR system. We anticipate that continued focus on the amygdala Dyn/KOR system will also elucidate novel ways to target the Dyn/KOR system to treat neuropsychiatric disorders.


Cell-based therapy for Parkinson's disease: A journey through decades toward the light side of the Force.
This review describes the history, development, and evolution of cell-based replacement therapy for Parkinson's disease (PD), from the first pioneering trials with fetal ventral midbrain progenitors to future trials using stem cells as well as reprogrammed cells. In the spirit of Tom Isaacs, the review takes parallels to the storyline of Star Wars, including the temptations from the dark side and the continuous fight for the light side of the Force. It is subdivided into headings based on the original movies, spanning from A New Hope to the Last Jedi.


Cobalt-Catalyzed C(sp(2) )-H Methylation by using Dicumyl Peroxide as both the Methylating Reagent and Hydrogen Acceptor.
The first cobalt-catalyzed direct methylation of a C(sp(2) )-H bond using dicumyl peroxide (DCP) as both the methylating reagent and hydrogen acceptor has been established. The reaction proceeded without the use of any additives, and was proven to be applicable to various amides bearing a 2-pyridinylisopropyl (PIP) directing group, providing an efficient access to o-methyl aryl amides with high functional-group tolerance. Preliminary mechanistic studies suggest a radical process would be involved in the catalytic process.


Fatty acid-binding proteins in the heart.
Long-chain fatty acids are important fuel molecules for the heart, their oxidation in mitochondria providing the bulk of energy required for cardiac functioning. The low solubility of fatty acids in aqueous solutions impairs their cellular transport. However, cardiac tissue contains several proteins capable of binding fatty acids non-covalently. These fatty acid-binding proteins (FABPs) are thought to facilitate both cellular uptake and intracellular transport of fatty acids. The majority of fatty acids taken up by the heart seems to pass the sarcolemma through a carrier-mediated translocation mechanism consisting of one or more membrane-associated FABPs. Intracellular transport of fatty acids towards sites of metabolic conversion is most likely accomplished by cytoplasmic FABPs. In this review, the roles of membrane-associated and cytoplasmic FABPs in cardiac fatty acid metabolism under (patho)physiological circumstances are discussed.


Readily acquired secondary infections of human and simian immunodeficiency viruses following single intravenous exposure in non-human primates.
Accumulating evidence suggests that exposed individuals may acquire multiple human immunodeficiency virus (HIV) infections more frequently than originally believed. As a result, circulating recombinant forms of HIV are emerging that are of particular concern in the AIDS epidemic and HIV vaccine development efforts. The aim of this study was to determine under what conditions secondary or superinfections of HIV or simian immunodeficiency virus (SIV) may be acquired under controlled settings in well-defined, non-human primate models. Retrospective analysis of macaques that had acquired apparent immunity upon infection with a defined attenuated SIV(mac) strain revealed that eight out of eight animals that were secondarily exposed to a new virus variant became infected with the new virus strain, but at low levels. Interestingly, similarly high frequencies of secondary infections were observed after early (4 months), as well as late (5 years), exposure following primary infection. As possible causes of susceptibility to secondary infections, perturbations in the immune system associated with exacerbated infections were then investigated prospectively. Results revealed that short-term immune-suppression therapy did not increase susceptibility to secondary infections. Taken together, data suggested that neither early- nor late-exposure immune-suppressive events following primary infection accounted for the observed high incidence of secondary infections. With HIV-1, the question of whether secondary infections with very closely related viral variants could occur in the chimpanzee model was addressed. In both animal models, secondary infections were confirmed, notably with relatively closely related SIV(mac) or HIV-1 strains, following a single exposure to the secondary virus strain. These findings reveal that secondary lentiviral infections may be acquired readily during different stages of primary infection, in contrast to co-infections, which are acquired at the moment of initial infection.


[Comparison of injection-related and local immunotherapy].
Allergen-specific immunotherapy is a well-accepted method in the management of respiratory allergic diseases, applied since over 90 years. Traditional immunotherapy is the practice of subcutaneous administering to subjects with allergy, increasing amounts of modified allergen to achieve hyposensitisation. Recently other routes of allergen administration were proposed including bronchial, nasal, oral and sublingual routes. Controlled trials failed to demonstrate the clinical efficacy and the safety of oral and bronchial administration. Nasal immunotherapy is also declining due to limited efficacy and special administration technique. The sublingual route is safe and efficacious. Unfortunately, up to date no well-designed controlled study comparing subcutaneous with sublingual methods of immunotherapy is available. Still several points need to be elucidated, including long lasting efficacy, mechanism of action, optimal dose, adherence to this therapy and cost-effectiveness. However, sublingual immunotherapy is now accepted by WHO as a valid alternative to the subcutaneous route and should be used in all patients who require immunotherapy and do not accept subcutaneous route of allergen administration. One question is presently beyond discussion: it is better to administer sublingual immunotherapy in patients with allergic diseases than not to give immunotherapy at all.


Risk factor research and prevention for anxiety disorders: introduction to the special series on risk and prevention of anxiety pathology.
In relation to treatment-related research in the United States, there is relatively little systematic effort focused on the combination of risk and prevention for anxiety pathology. This article broadly discusses risk factor research and prevention program development for anxiety psychopathology. The authors also specifically discuss papers in this special issue that are focused on these topics. Risk factor research should be used by clinical researchers to inform prevention programs, and reciprocally, prevention knowledge should be effectively utilized to drive new, clinically focused risk factor research.


The genus Peckia Robineau-Desvoidy (Diptera: Sarcophagidae) in the Brazilian Amazon: a new species, new records, descriptions of female terminalia and key to species.
Flesh flies of the genus Peckia Robineau-Desvoidy, 1830 were studied from the Brazilian Amazon region. The male terminalia of all species are illustrated. The female terminalia are described and illustrated for all species for which the female is known. The female terminalia of six species are described for the first time; those of seven species are redescribed and documented through new illustrations. A new species of the subgenus Pattonella Enderlein, 1928, Peckia (Pattonella) juruti sp. nov., is described. It is similar to Peckia (Pattonella) smarti (Lopes, 1941) in the shape of the cercus and distiphallus, but differs in the shape of the gonites, juxta and capitis. Peckia (Peckia) hillifera (Aldrich, 1916) is recorded from Brazil for the first time; Peckia (Euboettcheria) florencioi (Prado Fonseca, 1932) is newly reported for the Brazilian Amazon. A key to the 21 species of Peckia so far recorded from the Brazilian Amazon is provided, allowing the identification of both sexes where known. The females of only five of these species remain unknown.


Standardizing visual control devices for tsetse flies: east African Species Glossina fuscipes fuscipes and Glossina tachinoides.
Riverine species of tsetse are responsible for most human African trypanosomiasis (HAT) transmission and are also important vectors of animal trypanosomiasis. This study concerns the development of visual control devices for two such species, Glossina fuscipes fuscipes and Glossina tachinoides, at the eastern limits of their continental range. The goal was to determine the most long-lasting, practical and cost-effective visually attractive device that induces the strongest landing responses in these species for use as insecticide-impregnated tools in vector population suppression. Field trials were conducted in different seasons on G. f. fuscipes in Kenya, Ethiopia and the Sudan and on G. tachinoides in Ethiopia to measure the performance of traps and 2D targets of different sizes and colours, with and without chemical baits, at different population densities and under different environmental conditions. Adhesive film was used to enumerate flies at these remote locations to compare trapping efficiencies. The findings show that targets made from black and blue fabrics (either phthalogen or turquoise) covered with adhesive film render them equal to or more efficient than traps at capturing G. f. fuscipes and G. tachinoides. Biconical trap efficiency varied between 25% and 33% for the two species. Smaller 0.25 m×0.25 m phthalogen blue-black targets proved more efficient than the regular 1 m2 target for both species, by over six times for Glossina f. fuscipes and two times for G. tachinoides based on catches per m2. Overall, targets with a higher edge/surface area ratio were more efficient at capturing flies. Taking into account practical considerations and fly preferences for edges and colours, we propose a 0.5×0.75 m blue-black target as a simple cost-effective device for management of G. f. fuscipes and G. tachinoides, impregnated with insecticide for control and covered with adhesive film for population sampling.


Uncoupling proteins 1 and 2 (UCP1 and UCP2) from Arabidopsis thaliana are mitochondrial transporters of aspartate, glutamate, and dicarboxylates.
The Arabidopsis thaliana genome contains 58 members of the solute carrier family SLC25, also called the mitochondrial carrier family, many of which have been shown to transport specific metabolites, nucleotides, and cofactors across the mitochondrial membrane. Here, two Arabidopsis members of this family, AtUCP1 and AtUCP2, which were previously thought to be uncoupling proteins and hence named UCP1/PUMP1 and UCP2/PUMP2, respectively, are assigned with a novel function. They were expressed in bacteria, purified, and reconstituted in phospholipid vesicles. Their transport properties demonstrate that they transport amino acids (aspartate, glutamate, cysteine sulfinate, and cysteate), dicarboxylates (malate, oxaloacetate, and 2-oxoglutarate), phosphate, sulfate, and thiosulfate. Transport was saturable and inhibited by mercurials and other mitochondrial carrier inhibitors to various degrees. AtUCP1 and AtUCP2 catalyzed a fast counterexchange transport as well as a low uniport of substrates, with transport rates of AtUCP1 being much higher than those of AtUCP2 in both cases. The aspartate/glutamate heteroexchange mediated by AtUCP1 and AtUCP2 is electroneutral, in contrast to that mediated by the mammalian mitochondrial aspartate glutamate carrier. Furthermore, both carriers were found to be targeted to mitochondria. Metabolite profiling of single and double knockouts shows changes in organic acid and amino acid levels. Notably, AtUCP1 and AtUCP2 are the first reported mitochondrial carriers in Arabidopsis to transport aspartate and glutamate. It is proposed that the primary function of AtUCP1 and AtUCP2 is to catalyze an aspartateout/glutamatein exchange across the mitochondrial membrane and thereby contribute to the export of reducing equivalents from the mitochondria in photorespiration.


Steroids and hematopoiesis. II. The effect of steroids on in vitro erythroid colony growth: evidence for different target cells for different classes of steroids.
Androgenic steroids and their non-androgenic 5beta-H metabolites enhance the number of colonies of hemoglobin synthesizing cells grown from rat bone marrow in response to a standard (0.25 unit/ml) concentration of erythropoietin. The target cells for two steroids were found to be different. Cells influenced by the androgen, fluoxymesterone (fluoxy), resembled cells responding to erythropoietin in their cycle characteristics, as measured by tritiated thymidine suicide, and in their physical characteristics, as determined by velocity sedimentation gradient separation. Cells responding to etiocholanolone (etio) had a much lower tritiated thymidine suicide rate and different sedimentation velocities. Preincubation of marrow cells with etio for two hours was sufficient to enhance erythroid colony growth by 84%, whereas a similar incubation with fluoxy produced no increment. These studies demonstrate that different classes of steroids may influence in vitro erythropoiesis by acting on distinct populations of marrow cells. Fluoxymesterone appears to act through cells already committed to respond to erythropoietin, while etiocholanolone appears to act on a separate, perhaps more primitive population of marrow cells.


Particulate delivery systems for animal vaccines.
The requirements for veterinary vaccines are different to those of human vaccines. Indeed, while more side effects can be tolerated in animals than in humans; there are stricter requirements in terms of cost, ease of delivery (including to wildlife), and a need to develop vaccines in species for which relatively little is known in terms of molecular immunology. By their nature particulate vaccine delivery systems are well suited to address these challenges. Here, we review particulate vaccine delivery systems, ranging from cm-sized long-distance ballistic devices to nano-bead technology for veterinary species and wildlife.


Is damage in central nervous system due to inflammation?
The aim of this work was to review the inflammatory factors involved in central nervous system (CNS) inflammation and the damage associated to their participation in an inflammatory disease of CNS, multiple sclerosis in humans and experimental allergic encephalomyelitis in the murine model. Inflammation has an important repairing function, nevertheless frequently in the CNS inflammation is the cause of damage and it does not fulfill this repairing function as it happens in other compartments of the body. The inflammatory response in the CNS involves the participation of different cellular types of the immune system (macrophages, mast cells, T and B lymphocytes, dendritic cells) and resident cells of the CNS (microglia, astrocytes, neurons), adhesion molecules, cytokines and chemokines among other proteic components. During neuroinflammation chemotaxis is an important event in the recruitment of cells to the CNS. The lymphocyte recruitment implies the presence of chemokines and chemokine receptors, the expression of adhesion molecules, the interaction between lymphocytes and the bloodbrain barrier (BBB) endothelium, and finally their passage through the BBB to arrive at the site of inflammation. If this process is not controlled, is prolonged, inflammation loses its repairing function and can be the cause of damage. Usually neuroinflammation has the tendency to decline to damage, which would explain most of the CNS pathologies.


[Pharmacokinetics of apalcillin. Study of linearity].
Apalcillin is a new semi-synthetic penicillin active on the positive Gram bacteria, and on the enterobacteria, with a particular activity on Pseudomonas and Acinetobacter. The linearity study of the pharmacokinetic was carried out on 26 subjects who were given increasing doses (500, 1 000, 2 000, 3 000 mg) of apalcillin by the venous route. The dosages carried out by the HPLC and bacteriological methods, show a good correlation between the two methods. The serum concentrations, 5 mn. after injection, were respectively 72 micrograms/ml (500 mg); 145 micrograms/ml (1 g) ; 221 micrograms/ml (2 g) ; 290 micrograms/ml (3 g). Urinary excretion is around 20 %, and this, regardless of the dose. The dose increase seems to have no effect on the pharmacokinetic parameters, calculated on the basis of a bi- compartmental model. The areas under the time serum concentrations, increase proportionally, to the dose : 61 (500 mg) ; 146 (1 g) ; 285 (2 g) ; 367 (3 g) - micrograms/ml X h. the linear regression between the AUC (y) and the applied doses (X) is : y = 0,12 X + 14,27 ; r = 0,9046 ; n = 69. The correlation between the AUC and the doses is significant (p less than 0,001). The results obtained show that increasing the dosage has no effect on apalcillin pharmacokinetics, which appear linear.


Nitric oxide alterations following acute ductal constriction in the fetal lamb: a role for superoxide.
Acute partial compression of the fetal ductus arteriosus (DA) results in an initial abrupt increase in pulmonary blood flow (PBF), which is followed by a significant reduction in PBF to baseline values over the ensuing 2-4 h. We have previously demonstrated that this potent vasoconstricting response is due, in part, to an endothelin-1 (ET-1)-mediated decrease in nitric oxide synthase (NOS) activity. In addition, in vitro data demonstrate that ET-1 increases superoxide levels in pulmonary arterial smooth muscle cells and that oxidative stress alters NOS activity. Therefore, the objectives of this study were to determine the potential role of superoxide in the alterations of hemodynamics and NOS activity following acute ductal constriction in the late-gestation fetal lamb. Eighteen anesthetized near-term fetal lambs were instrumented, and a lung biopsy was performed. After a 48-h recovery, acute constriction of the DA was performed by inflating a vascular occluder. Polyethylene glycol-superoxide dismutase (PEG-SOD; 1,000-1,500 units/kg, n = 7) or PEG-alone (vehicle control group, n = 5) was injected into the pulmonary artery before ductal constriction. Six animals had a sham operation. In PEG-alone-treated lambs, acute ductal constriction rapidly decreased pulmonary vascular resistance (PVR) by 88%. However, by 4 h, PVR returned to preconstriction baseline. This vasoconstriction was associated with an increase in lung superoxide levels (82%), a decrease in total NOS activity (50%), and an increase in P-eNOS-Thr495 (52%) (P < 0.05). PEG-SOD prevented the increase of superoxide after ductal constriction, attenuated the vasoconstriction, preserved NOS activity, and increased P-eNOS Ser1177 (307%, P < 0.05). Sham procedure induced no changes. These data suggest that an acute decrease in NOS activity that is mediated, in part, by increased superoxide levels, and alterations in the phosphorylation status of the endothelial NOS isoform, underlie the pulmonary vascular response to acute ductal constriction.


The Finnish drinking culture: change and continuity in the past 40 years.
In the past 40 years, per capita consumption has increased dramatically in Finland. We study the core changes in drinking culture over this period by age and sex. We used data from the Finnish Drinking Habit Surveys carried out every 8 years in 1968-2008 (n = 16385, response rates 74-97%). Central measures included share of abstainers, frequency of drinking, amounts drunk per occasion and contexts of drinking (location, company, timing). Weekly drinking and the frequency of moderate drinking increased among both women and men but proportionately more among women and among respondents aged over 30 years. Amounts drunk per occasion and intoxication increased proportionately more among women and younger respondents. Drinking in home surroundings increased more than drinking in licensed premises, and home drinking increasingly occurred in the company of partners only. Drinking was in all periods heavily concentrated on the weekends and evenings. Finland has become a wet and permissive drinking culture, and there has been a fundamental cultural shift in women's drinking in particular. Increases in women's drinking have meant that men's drinking has also increasingly been brought to homes, as a part of spouses' shared activities, and pubs have lost their property as masculine strongholds. Intoxication has maintained its important position in the drinking culture, and drinking still takes place primarily in the evenings and weekends. If drinking cultures in present-day low and middle income countries develop similarly, strong increases in alcohol-related harm will follow.


Expression of the estrogen receptor beta in 37 surgically treated pulmonary sclerosing hemangiomas in comparison with non-small cell lung carcinomas.
Sclerosing hemangioma (SH) of the lung is an uncommon tumor with a predilection for middle-aged women. This special phenomenon prompted us to examine SH for the expression of ERalpha (human estrogen receptor) and ERbeta (a second isoform of estrogen receptor). To investigate the staining pattern of these tumors, we also stained lung tissues from patients with non-small cell lung carcinomas and nonneoplastic type II pneumocytes for comparison. Thirty-seven pulmonary SHs and 301 non-small cell lung cancers specimens were explored. Expression of ERalpha and ERbeta was immunohistochemically measured. The overall frequency of overexpression for ERbeta was 91.9%. It was detected in both female (in 91.4% of 35 cases) and male (in 100.0% of 2 tumors from men) patients. There was ERbeta overexpression in all 9 tumors of solid pattern, 6 of 7 tumors of papillary pattern, all 4 tumors of sclerotic pattern, 12 of 13 tumors of hemorrhagic pattern, and 3 of 4 tumors of mixed pattern. The staining pattern of the neoplastic cells of the SH was similar to that of type II pneumocytes adjacent to the tumor rather than that of non-small cell lung cancers, in which the frequency of ERbeta overexpression was 45.8%. However, there was no ERalpha detectable in these neoplasms. Estrogen receptor beta overexpression is very frequent in pulmonary SHs, which is similar to that of alveolar cells but quite different from non-small cell carcinoma.


[Induction of mutations in mammalian cells by the action of live vaccinal strains of poliomyelitis virus].
The attenuated strains' poliomyelitis virus induces mutagenesis in human and Chinese hamster cultured cells. The mutagenic action of the poliovirus is detected at chromosome and gene levels and directly depends on the multiplicity of cell infection. Possibilities for developing nonmutagenic antivirus vaccines are discussed.


Oral Chinese herbal medicine in reducing the recurrence of colorectal adenoma after polypectomy: A protocol for the systematic review and meta-analysis.
Colorectal adenoma (CRA) is a significant precancerous lesion of sporadic colorectal cancer (CRC). CRA is likely to recur after polypectomy, increasing the risk of CRC. Chinese herbal medicine (CHM) has been used to reduce CRA recurrence. This review aims to evaluate the effectiveness and safety of oral CHM in reducing CRA recurrence compared to other treatments (placebo, routine care, no treatment, and conventional medicine). We will search for randomised controlled trials (RCTs) from nine major biomedical databases in English and Chinese from their inception to July 2023. The RCTs that investigate the effects of oral CHM in reducing CRA recurrence compared to other treatments will be involved. We will exclude trials using CHM extract or external application of CHM, cohort study and cross-section study. The Cochrane Risk of Bias Tool version 2 will be used to assess the quality of included studies. Data will be analysed using Review Manager software 5.4 and STATA. The random effect model will be used. The heterogeneity of intervention effects will be tested by Chi2 (Cochrane Q) and I2 statistics. Funnel plots will assess publication bias if more than ten studies are included. Subgroup and sensitivity analysis will be conducted when possible. This review will discuss the effectiveness and safety of oral CHM in reducing CRA recurrence. It will show the critical information for clinicians in the decision-making process and countries to develop clinical guidelines on CRA management. Systematic review registration PROSPERO CRD42023324197.


4G/5G and A-844G Polymorphisms of Plasminogen Activator Inhibitor-1 Associated with Glioblastoma in Iran--a Case-Control Study.
Glioblastoma is a highly aggressive and malignant brain tumor. Risk factors are largely unknown however, although several biomarkers have been identified which may support development, angiogenesis and invasion of tumor cells. One of these biomarkers is PAI-1. 4G/5G and A-844G are two common polymorphisms in the gene promotor of PAI 1 that may be related to high transcription and expression of this gene. Studies have shown that the prevalence of the 4G and 844G allele is significantly higher in patients with some cancers and genetic disorders. We here assessed the association of 4G/5G and A-844G polymorphisms with glioblastoma cancer risk in Iranians in a case-control study. All 71 patients with clinically confirmed and 140 volunteers with no history and symptoms of glioblastoma as control group were screened for 4G/5G and A-844G polymorphisms of PAI-1, using ARMS-PCR. Genotype and allele frequencies of case and control groups were analyzed using the DeFinetti program. Our results showed significant associations between 4G/5G (p=0.01824) and A-844G (p=0.02012) polymorphisms of the PAI-1 gene with glioblastoma cancer risk in our Iranian population. The results of this study supporting an association of the PAI-1 4G/5G (p=0.01824) and A-844G (p=0.02012) polymorphisms with increasing glioblastoma cancer risk in Iranian patients.


Effect of radix paeoniae rubra on expression of p38 MAPK/iNOS/HO-1 in rats with lipopolysaccharide-induced acute lung injury.
To investigate the effect of radix paeoniae rubra (RPR) on expression of p38 mitogen activated protein kinase (MAPK)/iNOS/HO-1 in rats with lipopolysaccharide-induced acute lung injury and explore the molecular mechanism. Forty healthy male Wistar rats, weighing 200-250 g, aged 6-8 weeks (mean equal to 7 weeks), provided by the Experimental Center, Medical College, Wuhan University, Wuhan, China, were employed in this study. Under anesthesia with 7% chloraldurat (5 ml/kg body weight) through intraperitoneal injection, the trachea of the rat was exposed and an arterial puncture needle pricked into the trachea via cricothyroid membrane. Then they were randomly divided into five groups: 8 rats receiving 1 ml normal saline through the puncture needle (Group A), 8 receiving 1 ml lipopolysaccharide (LPS, 2.5 mg/kg, Group B), 8 receiving LPS and RPR (30 mg/kg, pumped through the femoral vein for 2 hours, Group C), 8 receiving RPR 2 hours before dripping LPS (Group D), and 8 receiving hemin (75 micromol/L through intraperitoneal injection) 18 hours before dripping LPS (Group E). After 6 hours of LPS dripping, blood samples were obtained through the carotid artery to perform blood gas analysis, then all the rats were exsanguinated to death and specimens of lung tissues were obtained. The pathomorphological changes of the lung tissues were observed. The expression of p38 MAPK/iNOS/HO-1, the neutrophil ratio, protein content in alveolar irrigating solution and malonaldehyde (MDA) content in the lung tissues were also detected. Compared with Group A, the expression of p38 MAPK, iNOS and HO-1 markedly increased in Groups B, C, D, and E (P < 0.01). But in Groups C, D and E the expression of p38 MAPK and iNOS were significantly lower than that of Group B, while expression of HO-1 was obviously higher than that of Group B (P < 0.05). The protein content, the ratio of neutrophils in bronchoalveolar lavage fluid (BALF), the content of MDA and the activities of serum NO in Group B were significantly higher than those of Group A (P < 0.01). There was a significant decrease in the level of arterial bicarbonate and partial pressure of oxygen in Group B (P < 0.01). Compared with Group B, these indexes of lung injury were significantly lower while the levels of arterial bicarbonate and partial pressure of oxygen increased significantly in Groups C, D and E (P < 0.05 or P < 0.01). Under light microscope, the pathological changes induced by LPS were significantly attenuated by RPR and hemin. The high expression of MAPK plays an important role in lipopolysaccharide-induced acute lung injury. Protective effect of RPR on lipopolysaccharide-induced acute lung injury may be related to the inhibition of the abnormal high expression of p38 MAPK/iNOS/HO-1.


[The smoking status of patients with acute coronary syndrome and effect of simple intervention on smoking cessation.].
To evaluate the abstinence rate and relapse rate of smoker with ACS after discharged from hospital, to evaluate the effect of simple smoking cessation interventions. 150 smokers with ACS were collected and was divided into simple intervention group (n = 87) and control group (n = 63), respectively, followed up for 6 months. 2 months, 6 months abstinence rate, relapse rate were compared between two groups, logistic regression model was used to analyzed the relevant factors for relapse. The smoking rate in patients with ACS was 31.14%, 6-month continuous abstinence rate and 6-month relapse rate was 64.6%, 36.4%, respectively. 6-month continuous abstinence rate and relapse rate between simple quit-smoking intervention group and control group showed no difference. Nicotine dependence score more than 4 points can be used as predictor of relapse. The smoking rate and the abstinence rate of smoker with ACS is higher than the general population, simple quit-smoking intervention do not increase the success rate of quit-smoking, indicated the need to strengthen the intervention in patients with ACS and smoking.


Multi-stable dye-doped dual-frequency twisted nematic liquid crystal smart window.
In this study, a novel, to the best of our knowledge, dye-doped dual-frequency liquid crystal multi-stable smart window is proposed. A chiral dopant with appropriate content was introduced into dye-doped dual-frequency liquid crystals to achieve an initial 180° twisted state. These liquid crystals can be switched to a nematic phase or a 360° twisted state by controlling the magnitude and frequency of the applied voltage. These nematic phase and 360° twisted states can exist stably for a long time because of the backflow effect and the anisotropic nature of the dual-frequency liquid crystal material. Due to the optical waveguide effect of dye-doped liquid crystals in the long-pitch state, the transmittance was different in nematic phase, 180°, and 360° twisted three zero-field stabilized absorption states. Finally, a multi-stable smart window is developed to switch between three zero-field stabilized absorption and scattering states.


Profiles in health: Multiple roles and health lifestyles in early adulthood.
Despite theoretical work suggesting that health behaviors should be considered in tandem rather than as individual and disconnected practices, little quantitative work has examined different lifestyles of health behavior practices. In addition, while a significant body of work has examined the association of holding multiple social roles and health outcomes, little work has examined how acquiring multiple roles in early adulthood influences health behavior. This article (a) illustrates the utility of examining health lifestyles-defined as constellations of individual health behavior practices-and (b) contributes to the literature on how accumulating multiple social roles is associated with health. Using two waves of the National Longitudinal Study of Adolescent to Adult Health (N = 12,098) a structural equation modeling approach is used to both (a) model latent health lifestyles from observed health behavior indicators, and (b) to predict health lifestyle membership based on changes in role-occupancy during the transition to early adulthood. Results suggest that the type of social role matters, with intensive obligatory roles associated with lifestyles of less tobacco, alcohol, and marijuana use but also with physical inactivity. In contrast, voluntary roles are associated with more active lifestyles but increased alcohol use. The results illustrate the importance of modeling overall health lifestyles rather than focusing only on individual health behaviors. The results also advance our understanding of how holding multiple roles is associated with health by extending the framework to an examination of health behavior.


Aspergillosis, a Natural Infection in Poultry: Mycological and Molecular Characterization and Determination of Gliotoxin in Aspergillus fumigatus Isolates.
Aspergillosis affects all types of birds; it causes the loss of specimens with high ecologic value and also leads to significant economic losses within the poultry industry. The main etiologic agent is Aspergillus fumigatus , a filamentary fungus with multiple virulence factors, such as gliotoxin (GT), which is an immunosuppressive epipolythiodioxopiperazine molecule. Necropsy was performed on 73 poultry from different provenances, all of which presented with a respiratory semiology compatible with aspergillosis. A mycological culture was performed on the injured lungs of diseased birds, as was chloroform extraction of the GT, a thin-layer chromatography analysis (TLC), and a histopathology analysis with hematoxylin-eosin and Grocott stainings. The A. fumigatus identification was confirmed by PCR, where the ITS 1 5.1-5.8S-ITS 2 fragment of the rDNA complex was amplified. The in vitro GT production was studied by TLC in the recovered isolates from A. fumigatus . Seven isolates of A. fumigatus were obtained and in six of them, GT-like compounds were detected. In a lung sample, a compound with the same retention time (RF) as the reference GT was detected; whereas RF compounds different from the GT standard were observed in three lung samples.


Prospective evaluation of the OKN K-SeT assay, a new multiplex immunochromatographic test for the rapid detection of OXA-48-like, KPC and NDM carbapenemases.
There is an urgent need for accurate and fast diagnostic tests capable of identifying carbapenemase producers. Here, we assessed the performance of a new multiplex lateral flow assay (OKN K -SeT) for the rapid detection of OXA-48-like, KPC and NDM carbapenemase-producing Enterobacteriaceae from culture colonies. Two hundred collection isolates with characterized β-lactamase content and 183 non-duplicate consecutive isolates referred to two National Reference Centres over a 2 month period in 2016 were used to evaluate the OKN K -SeT assay. The assay correctly detected all 42 OXA-48-like-, 27 KPC- and 30 NDM-producing isolates from the collection panel, including 7 isolates that co-produced NDM and OXA-181 carbapenemases. No cross-reactivity was observed with non-targeted carbapenemases ( n = 41) or with non-carbapenemase producers ( n = 60). Prospectively, all OXA-48-like ( n = 69), KPC ( n = 9) and NDM ( n = 19) carbapenemase-producing Enterobacteriaceae isolates were correctly detected, while 11 carbapenemase producers not targeted by the assay went undetected [VIM ( n = 8) and OXA-23/OXA-58-like ( n = 3)]. Overall, the sensitivity and specificity of the assay were 100%. The OKN assay is efficient, rapid and easy to implement in the workflow of a clinical microbiology laboratory for the confirmation of OXA-48, NDM and KPC carbapenemases. This test represents a powerful diagnostic tool as it enables the rapid detection of the most clinically important carbapenemases without the need for more costly and less frequently available molecular assays.


Origin of enantioselection in chiral alcohol oxidation catalyzed by Pd[(-)-sparteine]Cl2.
A kinetic investigation into the origin of enantioselectivity for the Pd[(-)-sparteine]Cl(2)-catalyzed aerobic oxidative kinetic resolution (OKR) is reported. A mechanism to account for a newly discovered chloride dissociation from Pd[(-)-sparteine]Cl(2) prior to alcohol binding is proposed. The mechanism includes (1) chloride dissociation from Pd[(-)-sparteine]Cl(2) to form cationic Pd(-)-sparteine]Cl, (2) alcohol binding, (3) deprotonation of Pd-bound alcohol to form a Pd-alkoxide, and (4) beta-hydride elimination of Pd-alkoxide to form ketone product and a Pd-hydride. Utilizing the addition of (-)-sparteine HCl to control the [Cl(-)] and [H(+)] and the resulting derived rate law, the key microscopic kinetic and thermodynamic constants were extracted for each enantiomer of sec-phenethyl alcohol. These constants allow for the successful simulation of the oxidation rate in the presence of exogenous (-)-sparteine HCl. A rate law for oxidation of the racemic alcohol was derived that allows for the successful prediction of the experimentally measured k(rel) values when using the extracted constants. Besides a factor of 10 difference between the relative rates of beta-hydride elimination for the enantiomers, the main enhancement in enantiodetermination results from a concentration effect of (-)-sparteine HCl and the relative rates of reprotonation of the diastereomeric Pd-alkoxides.


Actomyosin-dependent invasion of endothelial sprouts in collagen.
During sprouting angiogenesis-the growth of blood vessels from the existing vasculature-endothelial cells (ECs) adopt an elongated invasive form and exert forces at cell-cell and cell-matrix interaction sites. These cell shape changes and cellular tractions require extensive reorganizations of the actomyosin network. However, the respective roles of actin and myosin for endothelial sprouting are not fully elucidated. In this study, we further investigate these roles by treating 2D-migrating and 3D-sprouting ECs with chemical compounds targeting either myosin or actin. These treatments affected the endothelial cytoskeleton drastically and reduced the invasive response in a compound-specific manner; pointing toward a tight control of the actin and myosin activity during sprouting. Clusters in the data further illustrate that endothelial sprout morphology is sensitive to the in vitro model mechanical microenvironment and directs future research toward mechanical substrate guidance as a strategy for promoting engineered tissue vascularization. In summary, our results add to a growing corpus of research highlighting a key role of the cytoskeleton for sprouting angiogenesis.


An induced Ets repressor complex regulates growth arrest during terminal macrophage differentiation.
Defining the molecular mechanisms that coordinately regulate proliferation and differentiation is a central issue in development. Here, we describe a mechanism in which induction of the Ets repressor METS/PE1 links terminal differentiation to cell cycle arrest. Using macrophages as a model, we provide evidence that METS/PE1 blocks Ras-dependent proliferation without inhibiting Ras-dependent expression of cell type-specific genes by selectively replacing Ets activators on the promoters of cell cycle control genes. Antiproliferative effects of METS require its interaction with DP103, a DEAD box-containing protein that assembles a novel corepressor complex. Functional interactions between the METS/DP103 complex and E2F/ pRB family proteins are also necessary for inhibition of cellular proliferation, suggesting a combinatorial code that directs permanent cell cycle exit during terminal differentiation.