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pubmed_48_24980 | AIM
To evaluate safety, tolerability and pharmacokinetics of oral PF-05190457, an oral ghrelin receptor inverse agonist, in healthy adults.
METHODS
Single (SAD) and multiple ascending dose (MAD) studies were randomised, placebo-controlled, double-blind studies. Thirty-five healthy men (age 38.2 ± 10.4 years; body mass index 24.8 ± 3.1 kg m-2 [mean ± standard deviation]) received ≥1 dose (2, 10, 40 [divided], 50, 100, 150, and 300 [single or divided] mg) of PF-05190457 and/or placebo in the SAD. In the MAD study, 35 healthy men (age 39.7 ± 10.1 years; body mass index 25.9 ± 3.3 kg m-2 ) received ≥1 dose (2, 10, 40 and 100 mg twice daily) of PF-05190457 and/or placebo daily for 2 weeks.
RESULTS
PF-05190457 absorption was rapid with a Tmax of 0.5-3 hours and a half-life between 8.2-9.8 hours. PF-05190457 dose-dependently blocked ghrelin (1 pmol kg-1 min-1 )-induced growth hormone (GH) release with (mean [90% confidence interval]) 77% [63-85%] inhibition at 100 mg. PF-05190457 (150 mg) delayed gastric emptying lag time by 30% [7-58%] and half emptying time by 20% [7-35%] with a corresponding decrease in postprandial glucose by 9 mg dL-1 . The most frequent adverse event reported by 30 subjects at doses ≥50 mg was somnolence. PF-05190457 plasma concentrations also increased heart rate up to 13.4 [4.8-58.2] beats min-1 and, similar to the effect on glucose and ghrelin-induced GH, was lost within 2 weeks.
CONCLUSIONS
PF-05190457 is a well-tolerated first-in-class ghrelin receptor inverse agonist with acceptable pharmacokinetics for oral daily dosing. Blocking ghrelin receptors inhibits ghrelin-induced GH, and increases heart rate, effects that underwent tachyphylaxis with chronic dosing. PF-051940457 has the potential to treat centrally-acting disorders such as insomnia. | 10.1111/bcp.13127 |
pubmed_462_19637 | Five cases of hepatic tumor deemed unresectable by conventional techniques are presented to illustrate the potential benefit offered by complete hepatic vascular exclusion (Pringle maneuver associated with inferior vena cava clamping below and above the liver). The most extensive and difficult liver resections may be achieved, with possible venous reconstruction, if the clamping period is not interrupted. Hepatic vascular exclusion may exceed one hour, up to 85 minutes in this series, with a good liver tolerance, in the absence of preoperative liver dysfunction. The advantages and disadvantages of the ex situ extracorporeal liver resections performed under similar circumstances are discussed. The authors consider that the role of ex situ liver procedures should be very limited. | pubmed_462_19637 |
pubmed_76_23992 | 1. Forty-five outbred Wistar rats were randomly assigned to three experimental groups: GI, 10 non-diabetic control rats; GII, 10 alloxan-diabetic control rats; GIII, 25 alloxan-diabetic rats which received pancreaticoduodenal transplantation (PDT) from normal Wistar donor rats and were immunosuppressed with cyclosporin A (Cy-A), 10 mg kg body weight-1 day-1, administered intraperitoneally for 30 days. 2. In parallel, 15 alloxan-diabetic inbred Wistar rats received isogeneic PDT from normal Wistar donor rats. 3. Cy-A prevented graft rejection in the 15 surviving animals in group III. These observations were confirmed by clinical and biochemical parameters (body weight, urine output, water and food intake, blood and urinary glucose and plasma insulin) and by histology and immunohistochemistry of the pancreas. 4. However, Cy-A was associated with 60% of the infectious complications in transplanted rats leading to 40% mortality. Pulmonary infections were the main cause of death. There were no side effects of immunosuppression on the pancreas. Infections were not significant in inbred rats submitted to PDT. | pubmed_76_23992 |
pubmed_137_9809 | The aim of this work was to study the application of resin filling containing nanomaterials for the potential treatment of caries. Zinc nanoparticles (ZnO@NP, 50 nm) were chosen for their antimicrobial capacity against aerobic bacteria, and here, they have proved to be bactericidal against anaerobic bacterial strains (Streptococcus mutans, Streptococcus mitis, and Lactobacillus spp.). Potential mechanism of action is proposed based on microbiological assays and seems to be independent of oxidative stress because the nanoparticles are effective in microaerophilic conditions. The loading of nanoparticles on the demineralized dental surface and their infiltration power were significantly improved when ZnO@NP were carried by the resin. Overall, this material seems to have a high potential to become a one-step treatment for caries lesions. | 10.1155/2019/6367919 |
pubmed_1038_21717 | Previous studies showed that EGF is produced by salivary and duodenal glands and released in saliva and duodenal secretion. Using specific radioimmunoassay of EGF, this study showed that the salivary glands and duodenal mucosa contain high levels of EGF, reaching, respectively, about 38 and 4 micrograms/g of tissue weight. EGF immunoreactivity was also found in high amounts in the pancreatic tissue (20 micrograms/g) and the pancreatic juice (32 ng/mL), where the content of EGF was found to increase in response to feeding, cholecystokinin, or bombesin and to decrease after the administration of atropine and somatostatin. Studies on the binding of EGF revealed that pancreatic acinar membranes possess the specific and saturable EGF receptors with a high affinity sites with Kd of about 4.3 nM and binding capacity of about 62 fmol/mg of protein, and with low affinity sites with Kd of 21 nM and binding capacity of about 180 fmol/mg of protein. The observed high content of immunoreactive EGF in the pancreatic tissue and the presence of high and low affinity binding sites for EGF in the pancreatic acinar membranes, as well as the high EGF output in the pancreatic juice and its alterations in response to hormonal and postprandial stimulation, suggest an important role of EGF in pancreatic physiology. | 10.1007/BF02925987 |
pubmed_726_14157 | We developed a sensitive and rapid method for determination of ferulic acid, caffeic acid, vanillic acid, and paeoniflorin in rat plasma based on ultra high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). The separation of the four compounds was carried out on an AcQuity UHPLC™ BEH C18 column using a mobile phase consisting of acetonitrile and water (containing 0.1% formic acid). Electrospray ionization in positive and negative ion mode and multiple reaction monitoring was used to identify and quantify active components. All calibration curves gave good linearity (r > 0.991) over the concentration range from 4.24-2875 ngmL(-1) for all components. The precision of the in vivo study was evaluated by intraday and interday assays and the percentages of RSD were all within 10.6%. The recovery ranged from 60.2 to 77.9%. The method was successfully applied to pharmacokinetic study of all three aromatic acids and one monoterpene in rat plasma. Furthermore, we compared the pharmacokinetics profile of the four compounds in normal and primary dysmenorrhea rats' plasma following oral administration of Shaofu Zhuyu decoction (SFZYD) and its ethanol supernatant extract (SFE). | 10.1142/S0192415X13500481 |
pubmed_995_8759 | Extracellular fluid volume (ECF, [125I]iothalamate space), blood volume (BV, 51Cr-labeled erythrocyte space), and hematocrit were measured continuously to study the kinetics of fluid movements between intracellular, interstitial, and plasma compartments during water immersion (WI) at 38 degrees C in seven splenectomized and acutely nephrectomized dogs. ECF and plasma volume (PV) increased linearly during WI by 10 +/- 2 ml/kg (4% of initial ECF volume, P less than 0.05) and 12 +/- 2 ml/kg (33% of initial PV, P less than 0.05), respectively, above the control level by 120 min of WI. We estimate that 83% of the fluid entering the intravascular compartment is derived from the intracellular space at 120 min of WI. The results of this study indicate that WI leads to a sustained fluid movement of intracellular fluid toward the intravascular compartment. The increase in interstitial hydrostatic pressure (wick method) by 28.5 mmHg from the control level at 5 min of WI in response to the external water pressure exceeds the increase in mean capillary pressure by 10-11 mmHg relative to the control level. We postulate that this negative hydrostatic pressure gradient across the capillary wall leads to an increase in PV during WI. | 10.1152/ajpregu.1987.252.5.R972 |
pubmed_894_8257 | Diadenosine triphosphate (Ap3A) has been identified and quantified in human platelets using a coupled enzymatic assay specific for Ap3A, after fractionation of acidic extracts with high-performance liquid chromatography. Upon thrombin-induced aggregation, Ap3A is released together with the homologue diadenosine tetraphosphate (Ap4A). Extracts of human platelets do also contain enzymatic activities that degrade diadenosine tetraphosphate as well as diadenosine triphosphate. These enzymes, however, are not released during thrombin-induced aggregation of the platelets. | 10.1016/0006-291x(83)90997-x |
pubmed_714_15057 | Nucleotide diversity may be decreased when a different DNA sequence type appears in a population. This undesirable property in a genetic diversity index is demonstrated by mathematical examples. The possibility of this phenomenon in natural populations is briefly discussed. | 10.1007/pl00006604 |
pubmed_501_11573 | The effect of repeated exposure to an additive dose of long ultraviolet (UVA) radiation on the erythemogenic and therapeutic effects of middle ultraviolet (UVB) irradiation was investigated in 8 patients with psoriasis. The surface of the backs of these patients was divided into 2 parts, 1 of which received only UVB irradiation 4 times a week and the other UVA + UVB. UVB was provided by Philips TL-12 lamps and UVA by glass-filtered Philips TL-09 lamps. UVA was held constantly at 10 J/cm2, whereas UVB was increased. The erythemogenic effects of UVA + UVB and UVB alone were evaluated by 4 tests during the treatment to determine the minimal erythema dose (MED). Test I (at the start of the therapy) showed a photoaugmentative effect which was no longer apparent in test III (third week). Test III showed a reversal of the ratios of the MEDs of the sites irradiated with UVA + UVB and UVB (MED A + B/MED B). This is ascribed to the marked pigmentation which appeared after repeated irradiation with the UVA + UVB combination. Comparison showed for the improvement of the psoriasis no distinct differences between UVA + UVB irradiation and UVB alone, but the former had the cosmetic advantage of giving pleasing tan. | 10.1111/1523-1747.ep12524880 |
pubmed_401_22250 | Objective: This study aimed to evaluate the differential role of a high-fat diet (HF) or high-fructose diet (HFRU) on white adipose tissue and brown adipose tissue remodeling in C57BL/6 mice.Methods: The animals were randomly assigned to receive HF (50% of energy as lipids), HFRU (50% of energy as fructose), or a control diet (C, 10% of energy as lipids) for 12 weeks. Results: The HF group became overweight from the 7th week onwards, but both HF and HFRU groups showed hyperinsulinemia, oral glucose intolerance, and adverse adipose tissue remodeling. HF and HFRU groups showed interscapular brown adipose tissue whitening, tough the reduced QA [nuclei] suggested maximized brown adipocyte dysfunction due to the HFRU diet. In contrast, HF and HFRU diets exerted similar effects upon subcutaneous white adipocytes, with a similar average cross-sectional area. Immunohistochemistry confirmed the whitening enhancement with reduced UCP1 immunodensity in the HFRU group. Conclusion: In conclusion, HF and HFRU diets had indistinguishable effects upon white adipocyte morphology, but the HFRU diet provoked a more pronounced whitening than the HF diet after a 12-week protocol. These results point to the silent and harmful impact that excessive fructose has upon the metabolism of lean mice. | 10.1080/07315724.2022.2062686 |
pubmed_564_20729 | We report the first case of African histoplasmosis diagnosed in Brazil. The patient was an immigrant from Angola who had come to Brazil six months after the appearance of the skin lesion. The skin of the right retroauricular area was the only site of involvement. The diagnosis was established by direct mycologic examination, culture and by histopathologic examination of the lesion. The patient was successfully treated with Itraconazole 100mg a day for 52 days. No recurrent skin lesions were observed during the ten month follow-up period. | 10.1590/s0036-46651993000300013 |
pubmed_894_9099 | A novel human retrovirus (HTLV-II) was previously found associated with a T-cell variant of hairy-cell leukaemia. Molecular cloning demonstrates that the complete provirus genome is 8.8 kilobase pairs in size and is transmissible to uninfected cells. Two types of infectious deleted provirus were also characterized. The sequences of HTLV-II are distinct from those of HTLV-I. | 10.1038/305502a0 |
pubmed_199_920 | A 28-year-old woman developed leukopenia and slight cervical lymphadenopathy. Bone marrow aspiration and special stains established the diagnosis of acute monocytic leukemia. Following chemotherapy a complete hematologic remission was elicited. Seven months later, she consulted an ophthalmologist because of bilateral conjunctival lesions. Ophthalmologic examination showed subconjunctival, perilimbal grayish-pink infiltrates. A conjunctival biopsy disclosed sheets of mononuclear cells consistent with acute monocytic leukemia. Four months later, she developed cutaneous lesions in the face and chest wall. Subsequent biopsies of conjunctiva and skin and immunohistochemical demonstration of muramidase in the tumor cells supported the diagnosis of monocytic leukemia. Electron microscopic studies were particularly valuable and disclosed that more than 80% of the leukemic cells contained two types of cytoplasmic complexes of rough endoplasmic reticulum that displayed both tubular and helical configurations. These complexes differed morphologically from the ribosome-lamellar complexes observed in hairy cell leukemia and other hematologic disorders. | 10.1016/s0161-6420(85)34091-5 |
pubmed_495_8124 | Nosocomial infection is a serious issue in the hospital management. Countermeasures for this issue have been discussed from various points including clinical and laboratory medicine, nursing as well as hospital administration. This issue is of great importance to those of us medical practitioners, who engage in diagnosis and treatment of infectious diseases. The role of clinical microbiology laboratories for prevention of nosocomial infection includes performing epidemiological survey, giving information and education, and training and instruction to medical staff. In order to instruct and inspect the countermeasures against nosocomial infection, it is necessary to have a dedicated team in the hospital. We have organized an infection control team(ICT) to collect information and offer training and instruction regarding nosocomial infection. The ICT activities include 1) inspecting if the nosocomial infection control manual is followed correctly, 2) reporting the results of epidemiological survey regarding nosocomial infection, 3) offering the information regarding antimicrobial agents and disinfectants, 4) offering the information regarding the isolation of microorganisms in the hospital and their antimicrobial sensitivities, 5) cost calculation for nosocomial infection control. | pubmed_495_8124 |
pubmed_147_4791 | To elucidate a relationship between changes in focal brain temperature and severity of abnormal brain activity, epileptiform discharges and behavioral seizures were induced by Penicillin G in anesthetized rats, and focal brain-temperature was measured. Penicillin G was injected into the right primary sensorimotor cortex (400IU/μl). After the injection, epileptiform discharges induced a temperature increase gradually by 0.65±0.24°C. Moreover, when behavioral seizures were induced by reducing the anesthesia level, the temperature was raised by 0.26±0.22°C. These results suggest that elevation of the focal brain temperature is associated with the severity of epileptic activity. | pubmed_147_4791 |
pubmed_681_12150 | Six patients with a nonunion of the humeral diaphysis after intramedullary nailing were treated with a wave plate and autologous bone graft but without removal of the intramedullary implant. The mean duration of the nonunion was 19 months (range, 6-36 months). At a mean follow-up of 12 months (range, 6-18 months), all six nonunions had healed, and patient satisfaction was high. Five patients had regained full shoulder function. One patient, who was treated for a rotator cuff tear before the humeral fracture, had a satisfactory functional outcome. Elbow motion was full in all but one patient. One patient had a postoperative radial nerve palsy, which recovered partially but did not require further surgery. This report suggests that healing of humeral nonunions can be achieved in the presence of intramedullary hardware. | 10.1016/s1058-2746(03)00044-2 |
pubmed_993_6190 | Steady-state diffusing capacity (DLCOSS2), studied in healthy nonsmokers, was significantly higher in five old men when seated than when supine, but was unchanged in five young men. However, "corrected" for the increased ventilation, it decreased in the young--but not in the old--when erect compared with when supine. The change of DLCOSS2 in the young during the first 20 min when seated was related to a change of the fractional dead space ventilation (VD/VT)mThe old showed less venous admixture when seated than when supine, whereas VD/VT and regional ventilation-perfusion index of the lung bases was the same in both positions. The decrease in venous admixture was probably due to the closing capacity (CC) being less than the functional residual capacity (FRC) when seated. The elimination of closed off regions when seated made more pulmonary capillaries available for diffusion. | 10.1152/jappl.1975.38.3.418 |
pubmed_391_7159 | The antiviral action of cyclopentenone prostaglandins (PGs) is generally associated with alterations in the synthesis and/or maturation of specific virus proteins. In particular, inhibition of Sendai virus (SV) replication in African green monkey kidney cells by PGA1 has been shown to be a cell-mediated event, due to alterations in SV protein glycosylation and accompanied by the induction of a cellular polypeptide of Mr 74K. In this report we identify this protein as a heat shock protein (HSP) related to the major 70K HSP group (HSP70). Induction of HSP70 synthesis by PGA1 was found to be dose-dependent, and an accumulation of HSP70 comparable to that occurring after heat shock could be obtained at concentrations of PGA1 that did not inhibit macromolecular synthesis in uninfected cells, but caused a dramatic block of virus replication in SV-infected cells. Induction of HSP70 by PGA1 occurred at the transcriptional level and was not affected by SV infection. HSP70 synthesis was evident between 2 and 3 h after PGA1 treatment, maximal at 12 h and went back to control levels by 26 h after the addition of PGA1, thus preceding virus protein synthesis. Finally, of several PGs tested, only those which possess antiviral activity induced the synthesis of HSP70. These results, together with the observation that suppression of HSP70 synthesis by actinomycin D also abolishes the PGA1-induced alteration of SV glycoproteins, suggest that HSP70 could play a role in the block of virus replication by cyclopentenone PGs. | 10.1099/0022-1317-72-8-1877 |
pubmed_443_4968 | We previously demonstrated that oxysterols inhibit the growth of experimental glioblastoma induced in the rat brain cortex. Mechanism of action of these compounds remains obscure. In this study, we investigated the effect of 7beta-hydroxycholesterol (7beta-OHCH) and 7ketocholesterol (7k-CH) on the growth and MAP kinase activity in three in vitro biological models: rat astrocyte primary cultures, primary cultures treated by dibutyryl-cAMP (reactive cells), and the C6 glioma cell line. The oxysterols are not lethal to primary astrocytes, even if MAP kinase activity is decreased, particularly when cells were treated with 7k-CH. Both oxysterols are toxic to reactive astrocytes, and as compared with untreated primary cultures, they amplified the MAP kinase activity decrease. However, the mechanism of action of oxysterols on reactive astrocytes seems not to be linked to the MAP kinase pathway. In highly proliferating C6 cell lines, only 7beta-OHCH has an antiproliferative effect and is cytotoxic. The inhibition of MAP kinase activity is a function of 7beta-OHCH concentration. PD098059, a MAP kinase pathway inhibitor, has only a time-limited antiproliferative effect on C6 cell growth. We conclude that in C6 cells, the MAP kinase activity decrease is correlated with the toxic effect of 7beta-OHCH and occurs at first stages of 7beta-OHCH action. | 10.1002/(SICI)1097-4547(19980701)53:1<38::AID-JNR5>3.0.CO;2-K |
pubmed_32_6976 | Within the past three decades, extensive research has been carried out with the aim to prevent graft rejection by minimizing the side effects related to the use of immunosuppressants. The major goal in transplantation research remains the development of strategies that would allow one to achieve a state of donor-specific unresponsiveness in order to promote a condition of true tolerance without the need of immunosuppressants. Recent evidence has been provided that this is a pursuing goal, at least in experimental animals. The thymus plays the major role in the development of self-tolerance, and initial work in the late 1960s indicated that the thymus also plays a critical role in the induction of acquired tolerance to exogenous antigens. Recently, the interest in acquired thymic tolerance has been renewed by the observation that, in the rat, the thymus is an immunologically privileged site in which isolated pancreatic islets can be engrafted and survive indefinitely. Moreover, intrathymic injection of the islets induced donor-specific unresponsiveness, which allowed survival of a second donor-strain islet cell allograft transplanted into an extrathymic site. These findings on cellular allografts have been extended to vascularized organ allografts.(ABSTRACT TRUNCATED AT 250 WORDS) | 10.1681/ASN.V591639 |
pubmed_65_13198 | This article compares extremely low frequency (ELF) magnetic field exposures measured by placing EMDEX Lite personal exposure meters (PEMs) at the head, chest, and waist level for a group of office workers. Twenty-three volunteers were solicited to wear three PEMs simultaneously; one was attached to a baseball cap worn on the head, one was attached to a band and worn around the neck (positioned on the chest), and one was worn in a belted pouch around the waist (positioned on the right side of the hip). The effect of PEM placement was evaluated by comparing full-shift average exposures and daily maximum or peak exposure. The results of this investigation indicate that time-weighted average magnetic field exposures determined at the hip provide the highest mean exposure estimates. Averages of the full-shift mean magnetic field measurements taken at hip and head levels were statistically greater than measurements taken at the chest level by 33 and 22%, respectively. Comparisons of the maximum or peak magnetic field exposures by body position indicate that the hip position produced an average exposure estimate that was 136% greater than the average head-level measurement. Results suggest that for office workers PEM meter placement on the body does not produce large differences in full-shift average ELF magnetic flux density exposures. However, the hip position produced the largest daily maximum or peak exposures. It is recommended that PEMs be placed on the hip for exposure assessments in office environments, because this placement is the most commonly used, the most convenient, and resulted in the highest magnetic field exposures. | 10.1080/00028899908984486 |
pubmed_147_5195 | The phenotypic description of SHORT syndrome (OMIM- 269880) is expanding since its initial description in 1975. There have been 26 case reports till date but the genetic locus of this syndrome is elusive. Involvement of PITX2 gene initially envisaged is probably is not the only gene involved but has an important role to play in ocular development. Our case did not demonstrate mutation in PITX2 gene. Here, we report a case of SHORT syndrome with two new unreported features deviated nasal septum and cryptorchidism and stress on lipodystrophy, a cardinal feature but not a part of the pneumonic SHORT. | 10.1007/s13312-013-0099-8 |
pubmed_122_14679 | The nuclear pore complex (NPC) is a proteinaceous assembly that regulates macromolecular transport into and out of the nucleus. Although the structure of its scaffold is being revealed in increasing detail, its transport functionality depends upon an assembly of intrinsically disordered proteins (called FG-Nups) anchored inside the pore's central channel, which have hitherto eluded structural characterization. Here, using high-resolution atomic force microscopy, we provide a structural and nanomechanical analysis of individual NPCs. Our data highlight the structural diversity and complexity at the nuclear envelope, showing the interplay between the lamina network, actin filaments, and the NPCs. It reveals the dynamic behaviour of NPC scaffolds and displays pores of varying sizes. Of functional importance, the NPC central channel shows large structural diversity, supporting the notion that FG-Nup cohesiveness is in a range that facilitates collective rearrangements at little energetic cost. Finally, different nuclear transport receptors are shown to interact in qualitatively different ways with the FG-Nups, with particularly strong binding of importin-β. | 10.26508/lsa.201800142 |
pubmed_1105_22875 | Lung volume reduction surgery (LVRS) is performed as surgical therapy for severe pulmonary emphysema. In assessing diagnostic imaging indications, emphysematous change is the strongest in the thoracic computed tomography (CT), while the accumulation decrease is most remarkable in ventilation scintigram and lung perfusion scintigram. Preoperative evaluation of imaging using multidetector-row CT (MDCT) and scintigram were performed, and the multiplanar reconstruction (MPR) image of the MD CT and the single photon emission CT (SPECT) image of the scintigram were fused by the workstation. It was possible to evaluate the excision and the range of LVRS easily by looking at the fused image, and it was useful in deciding on the surgical approach. It is believed that accurate, comprehensible imaging information contributed to an improvement in the surgical outcome of LVRS. | pubmed_1105_22875 |
pubmed_346_12328 | Eight insulin-dependent adolescents (4 boys, 4 girls) participated in an 8-wk program of supervised exercise, and 8 matched controls were encouraged to exercise on their own without supervision. All 16 subjects were asked to follow a standard ADA diet plan, kept a self-reported log of caloric intake, and met with a dietitian weekly to review their diets. Exercise for the supervised subjects was scheduled between the routine afternoon snack and the evening meal, and subjects were asked not to consume additional food on exercise days. After the 8-wk program, glycemic control, as measured by glycosylated serum albumin and blood glucose values (but not by glycosylated hemoglobin), improved in the supervised-exercise group despite reduced daily insulin dosage. Cardiorespiratory fitness, as measured by voluntary maximum treadmill time (Bruce protocol) and submaximal exercise heart rates, also improved. No changes were observed in the unsupervised control group. | 10.2337/diacare.10.5.589 |
pubmed_520_18982 | Agrochemicals frequently undergo various chemical and metabolic transformation reactions in the environment that often result in a wide range of derivates that must be comprehensively characterized to understand their toxicity profiles and their persistence and outcome in the environment. In the development phase, this typically involves a major effort in qualitatively identifying the correct chemical isomer(s) of these derivatives from the many isomers that could potentially be formed. Liquid chromatography-mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy are often used in attempts to characterize such environment transformation products. However, challenges in confidently correlating chemical structures to detected compounds in mass spectrometry data and sensitivity/selectivity limitations of NMR frequently lead to bottlenecks in identification. In this study, we use an alternative approach, infrared ion spectroscopy, to demonstrate the identification of hydroxylated derivatives of two plant protection compounds (azoxystrobin and benzovindiflupyr) contained at low levels in tomato and spinach matrices. Infrared ion spectroscopy is an orthogonal tandem mass spectrometry technique that combines the sensitivity and selectivity of mass spectrometry with structural information obtained by infrared spectroscopy. Furthermore, IR spectra can be computationally predicted for candidate molecular structures, enabling the tentative identification of agrochemical derivatives and other unknowns in the environment without using physical reference standards. | 10.1021/acs.est.2c03210 |
pubmed_94_4040 | Physical exercise can improve cognitive functions and promote learning and memory, especially when performed in close temporal proximity to the encoding of information. This benefit may occur due to circulating stress hormones released in response to acute exercise. When administered after encoding, acute stress typically enhances the consolidation of emotional stimuli. However, whether acute exercise also selectively modulates emotional memories remains to be explored. Likewise, the potential role of sex in moderating these effects has not been addressed so far. Here, we tested whether a single bout of aerobic exercise after learning boosts the consolidation and thus long-term memory for emotional versus neutral visuospatial stimuli. Healthy men and women learned an object-location task and subsequently were exposed to a vigorous-treadmill running task or control intervention. Memory was assessed 24 h later. Acute exercise significantly increased heart rate and salivary cortisol in both sexes and selectively facilitated the consolidation of emotional stimuli. In particular, we found improved memory for negative items in women and better recall of positive items in men following exercise exposure. This memory benefit was positively related to the increase in heart rate and cortisol in both men and women, suggesting that the favorable effects of acute exercise on emotional memory may be mediated via a co-activation of the sympathetic nervous system and the hypothalamus-pituitary-adrenocortical axis. Our findings thereby provide first evidence for the improvement of emotional memory consolidation by acute physical exercise that appears to rely on similar neuroendocrine mechanisms as psychosocial stressors. Given that exercise is healthy, cost-effective and practical in nature, it constitutes an ideal behavioral intervention strategy for boosting memory in clinical and educational settings alike. | 10.1016/j.nlm.2020.107252 |
pubmed_813_12610 | Alveolar macrophages play a key role in the development of silicosis by releasing a host of mediators, such as, cytokines and chemokines, which contribute to a complex network of interactions that result in the onset of lung injury, inflammation, and potentially fibrosis. Using a murine macrophage cell line, RAW 264.7, we exposed the cells to cristobalite-silica (35 micrograms/cm(2)) in the presence or absence of antioxidants and various modifiers of cellular antioxidant status. Treatment with dimethyl sulfoxide, extracellular glutathione, or N-acetyl-L-cysteine (NAC) decreased cristobalite-induced tumor necrosis factor (TNF)-alpha mRNA levels by 40%, 20%, and 42%, respectively. TNF-alpha protein levels were decreased by 90%, 32%, and 53%, respectively. Cristobalite-induced macrophage inflammatory protein (MIP)-2 mRNA levels were reduced by 52%, 38%, and 57%, with DMSO, GSH, and NAC treatment, respectively. Both MIP-1alpha and MIP-1beta mRNA levels were reduced at a magnitude similar to the reduction in TNF-alpha mRNA levels, whereas monocyte chemotactic protein (MCP)-1 mRNA levels were reduced at a magnitude similar to the reduction in MIP-2 mRNA levels following antioxidant treatment. These results suggests that the macrophage response to cristobalite exposure is mediated at least in part by oxidant stress. | 10.1006/taap.1999.8716 |
pubmed_640_188 | Newborn specific-pathogen-free mice (SPF) were separated from their mothers shortly after birth and immediately reallocated at random to foster mothers, each of which received eight young. Under these conditions, the growth rate and adult size of the young were profoundly and lastingly conditioned by some unidentified influence exerted by the foster mother. In SPF mice nursed by their own mothers, the diet of the latter during gestation and lactation, or during lactation alone, conditioned the weight of the young at weaning time, and throughout their whole life span. Lasting depression of growth has been achieved by minor alterations of the dam's diet, for example by lowering its content in magnesium, or in lysine and threonine. The growth-depressing effect so achieved persisted throughout the whole life-span of the young, even though they were given at weaning time and constantly thereafter unlimited amounts of an optimum diet. In contrast, the weight-depressing effect of a diet deficient in lysine and threonine administered to adult animals was completely and rapidly reversible when a complete diet was later substituted for the deficient one. Depression of growth resulting from nutritional experiences during gestation or lactation did not seem to affect adversely the health of the young, or to decrease their longevity. In fact, the results of two experiments in which the animals nursed by mothers on different diets, were kept undisturbed and on optimum diets throughout their whole life span, suggest that the smaller animals had a greater average life expectancy than the larger ones. | 10.1084/jem.127.4.783 |
pubmed_708_22741 | Environmental factors may have significant adverse effects on the developing fetus. Prescribed and illicit drugs, environmental chemicals, physical factors, and maternal diseases may affect the developing fetus directly or may interact with genetic factors to cause birth defects. | 10.1016/s0025-7125(16)30562-4 |
pubmed_6_13163 | In this work, a colorimetric and fluorescent dual mode sensor based on lysosome-targeted CDs has been desirably implemented to identify Fe3+ fluctuations in vitro and in vivo. By simple one-pot hydrothermal carbonization of dried field mint, yellow-fluorescent CDs were directly fabricated without the assistance of other reagents and hold exceptional stability, superior biocompatibility as well as ultra-low cytotoxicity. Results indicated that as-prepared CDs can provide a rapid, reliable, and highly selective recognition of Fe3+ with a linear range of 0 μM-400 μM and a detection limit of 0.037 μM. Impressively, it was found that as-developed CDs can successfully target lysosome with high colocalization coefficient (0.85) and responds to fluctuations of Fe3+ in living cells. Further, acquired CDs was ingeniously devoted to Escherichia coli imaging. Besides, obtained CDs was eventually utilized to track the variation of Fe3+ in vivo system. A preliminary research expresses that as-synthesized CDs can function as an effective tool to detect Fe3+ in vitro and in vivo and thus indicates the promising applicability for disease detection in physiology and pathology in the future. | 10.1016/j.talanta.2021.122423 |
pubmed_486_15883 | BACKGROUND
Fatty infiltration, inflammation, and apoptosis are common degenerative changes in patients with chronic rotator cuff tears that can lead to muscle atrophy and can even result in massive irreparable rotator cuff tears. Some data have demonstrated the proregenerative, anti-inflammatory, and anti-apoptotic properties of stem cell-derived exosomes in some orthopaedic disorders, but their effect on torn rotator cuff muscles has never been investigated.
PURPOSE
To study the effect of exosomes isolated from human adipose-derived stem cells (ASCs-Exos) on muscle degeneration, regeneration, and biomechanical properties in a rat model of a massive rotator cuff tear (MRCT).
STUDY DESIGN
Controlled laboratory study.
METHODS
A bilateral supraspinatus and infraspinatus tenotomy was performed on rats to create an MRCT model. Forty-two rats were randomly assigned to 3 groups: the sham surgery group, the saline group (lesions treated with a saline injection), and the ASCs-Exos group (lesions treated with an ASCs-Exos injection). Wet muscle weight, fatty infiltration, inflammation, vascularization, regeneration, and biomechanical properties were evaluated at 8 and 16 weeks after surgery.
RESULTS
The results revealed that the ASCs-Exos treatment could prevent the atrophy, fatty infiltration, inflammation, and vascularization of muscles in the MRCT model (P < .001). Additionally, the myofiber regeneration and biomechanical properties of ASCs-Exos-treated rotator cuffs were significantly elevated compared with those in the saline-treated group (P < .001).
CONCLUSION
This study demonstrates that ASCs-Exos can effectively decrease atrophy and degeneration and improve muscle regeneration and biomechanical properties in torn rotator cuff muscles.
CLINICAL RELEVANCE
ASCs-Exos can be used as a new cell-free approach to prevent the muscle degeneration associated with torn rotator cuffs and may be helpful to repair torn rotator cuffs. Nevertheless, further work needs to be done in a large animal model owing to the inherent regenerative potential possessed by rodents. | 10.1177/0363546519876323 |
pubmed_1037_10738 | In the past few years significant advances made in the field of neuromodulation have led to practical therapeutic strategies for children with medically refractory epilepsy. Here, we briefly discuss the various options that are currently available including vagus nerve stimulation, responsive neurostimulation, deep brain stimulation, chronic subthreshold cortical stimulation, as well as repetitive transcranial magnetic and transcranial direct current stimulation. The current indications, proposed mechanisms, method of administration, efficacy, adverse effects, and mention of clinical trials currently in enrollment or development are discussed. | 10.1016/j.spen.2021.100918 |
pubmed_862_19885 | Granulocyte-colony-stimulating factor (G-CSF) is used for the mobilization of hemopoietic stem cells in healthy donors. It has a number of common side effects such as bone pain, which resolve rapidly after administration is discontinued. Recent publications have raised concern that it might act as a trigger for the development of hematologic malignancy in susceptible individuals, possibly by causing genomic instability, but to date there is no evidence that healthy volunteer donors who receive G-CSF are at any increased risk. Ongoing studies aim to confirm whether or not G-CSF can cause chromosomal abnormalities in healthy donors. In the UK, the British Bone Marrow Registry and Anthony Nolan Trust give G-CSF to donors who have agreed to donate peripheral blood stem cells. It is recommended by the UK Registries at present that all stem cell donors are given updated information explaining the current uncertainties with regard to the use of G-CSF before they give informed consent to its administration. This information is based on a statement agreed by the World Marrow Donor Association for use by individual donor registries. Further, it is our current practice that all donors who have received G-CSF, as well as marrow donors who do not, should be under regular review for at least 10 years to allow the occurrence of any long-term adverse events to be documented. | 10.1111/j.1537-2995.2008.01694.x |
pubmed_153_3619 | The technical challenge in proving that a given expressed pseudogene is in fact translated into a functional protein is specificity. To circumvent this challenge, one approach is to use PCR in order to generate a series of clones that allow expression of the protein of interest either native or fused to a tag, which can facilitate purification, detection, and complementation in both bacterial and mammalian cells. This approach allows an assessment of whether a putative pseudogenic protein possesses enzymatic activity, to identify its subcellular localization and to test its capacity to complement the parental homologue. | 10.1007/978-1-4939-0835-6_16 |
pubmed_880_18568 | Klebsiella pneumoniae is a pathogen of increasing concern because of multidrug resistance, especially due to K. pneumoniae carbapenemases (KPCs). K. pneumoniae must acquire iron to replicate, and it utilizes iron-scavenging siderophores, such as enterobactin (Ent). The innate immune protein lipocalin 2 (Lcn2) is able to specifically bind Ent and disrupt iron acquisition. To determine whether K. pneumoniae must produce Lcn2-resistant siderophores to cause disease, we examined siderophore production by clinical isolates (n = 129) from respiratory, urine, blood, and stool samples and by defined siderophore mutants through genotyping and liquid chromatography-mass spectrometry. Three categories of K. pneumoniae isolates were identified: enterobactin positive (Ent(+)) (81%), enterobactin and yersiniabactin positive (Ent(+) Ybt(+)) (17%), and enterobactin and salmochelin (glycosylated Ent) positive (Ent(+) gly-Ent(+)) with or without Ybt (2%). Ent(+) Ybt(+) strains were significantly overrepresented among respiratory tract isolates (P = 0.0068) and β-lactam-resistant isolates (P = 0.0019), including the epidemic KPC-producing clone multilocus sequence type 258 (ST258). In ex vivo growth assays, gly-Ent but not Ybt allowed evasion of Lcn2 in human serum, whereas siderophores were dispensable for growth in human urine. In a murine pneumonia model, an Ent(+) strain was an opportunistic pathogen that was completely inhibited by Lcn2 but caused severe, disseminated disease in Lcn2(-/-) mice. In contrast, an Ent(+) Ybt(+) strain was a frank respiratory pathogen, causing pneumonia despite Lcn2. However, Lcn2 retained partial protection against disseminated disease. In summary, Ybt is a virulence factor that is prevalent among KPC-producing K. pneumoniae isolates and promotes respiratory tract infections through evasion of Lcn2. | 10.1128/IAI.05114-11 |
pubmed_224_893 | A brief description of a nuclear magnetic resonance (NMR) imaging system and preliminary results from its clinical evaluation in the study of various central nervous system diseases are presented. Particular attention is paid to NMR capabilities for soft tissue discrimination, topographical demarcation, and specificity of diagnosis. Two imaging sequences were used: (a) Spin echo measurements with four sets of imaging parameters revealed the different appearances of normal and pathological structures. (b) Inversion recovery images showed marked gray-white matter contrast and clear depiction of pathological lesions. Finally, a number of measurements of longitudinal (T1) and transverse (T2) relaxation times of normal and pathological tissues were carried out. | 10.1097/00004728-198306000-00016 |
pubmed_48_15145 | Human outbreaks with avian influenza have been, so far, constrained by poor viral adaptation to non-avian hosts. This could be overcome via co-infection, whereby two strains share genetic material, allowing new hybrid strains to emerge. Identifying areas where co-infection is most likely can help target spaces for increased surveillance. Ecological niche modeling using remotely-sensed data can be used for this purpose. H5N1 and H9N2 influenza subtypes are endemic in Egyptian poultry. From 2006 to 2015, over 20,000 poultry and wild birds were tested at farms and live bird markets. Using ecological niche modeling we identified environmental, behavioral, and population characteristics of H5N1 and H9N2 niches within Egypt. Niches differed markedly by subtype. The subtype niches were combined to model co-infection potential with known occurrences used for validation. The distance to live bird markets was a strong predictor of co-infection. Using only single-subtype influenza outbreaks and publicly available ecological data, we identified areas of co-infection potential with high accuracy (area under the receiver operating characteristic (ROC) curve (AUC) 0.991). | pubmed_48_15145 |
pubmed_648_22515 | Previous studies show that anogenital swelling patterns of pregnant chimpanzees in captivity are correlated with the female's age during pregnancy and are associated with changes in social behavior. The purpose of the present study was to investigate whether the anogenital swelling patterns of free-ranging pregnant chimpanzees resemble those reported for captive chimpanzees. We reviewed the records of 47 pregnancies experienced by 20 female chimpanzees living in Gombe National Park from 1975 to 1992. Percentage scores for swelling during each trimester and for the overall occurrence of various levels of swelling were obtained by dividing the frequency by the total number of days the subject was observed (i.e., 28 days of swelling/165 days observation = 17.2% anogenital swelling for that pregnancy). Subjects exhibited anogenital swelling an average of 25.1% of the days observed during pregnancy, yet reached maximum only 9.4% of the time. Anogenital swelling occurred less frequently as pregnancy progressed, averaging 40.8, 27.3, and 2.7% in the first, second, and third trimesters, respectively. As seen in captive chimpanzees, young pregnant females at Gombe showed anogenital swelling more often than did older ones (r = -.65, P < .0001). These findings are consistent with reports of behavior associated with anogenital swelling (e.g., intercommunity transfer of young females exhibiting anogenital swelling). © 1993 Wiley-Liss, Inc. | 10.1002/ajp.1350310202 |
pubmed_692_16918 | Medical imaging studies increasingly use longitudinal images of individual subjects in order to follow-up changes due to development, degeneration, disease progression or efficacy of therapeutic intervention. Repeated image data of individuals are highly correlated, and the strong causality of information over time lead to the development of procedures for joint segmentation of the series of scans, called 4D segmentation. A main aim was improved consistency of quantitative analysis, most often solved via patient-specific atlases. Challenging open problems are contrast changes and occurance of subclasses within tissue as observed in multimodal MRI of infant development, neurodegeneration and disease. This paper proposes a new 4D segmentation framework that enforces continuous dynamic changes of tissue contrast patterns over time as observed in such data. Moreover, our model includes the capability to segment different contrast patterns within a specific tissue class, for example as seen in myelinated and unmyelinated white matter regions in early brain development. Proof of concept is shown with validation on synthetic image data and with 4D segmentation of longitudinal, multimodal pediatric MRI taken at 6, 12 and 24 months of age, but the methodology is generic w.r.t. different application domains using serial imaging. | 10.1109/ISBI.2014.6868113 |
pubmed_467_8543 | Forests are important carbon pools as they provide pathway to mitigate climate change. Quantification of forest carbon has gained momentum after Paris Agreement in 2015. This information is a prerequisite for REDD+ implementation and carbon trading. Temperate and subtropical mountain systems of Khyber Pakhtunkhwa province host about one third of Pakistan's 4.51 million ha forests. Present study estimated forest carbon stocks in the Khyber Pakhtunkhwa province of Pakistan. The data was collected from 449 sites in different forests across the province using a stratified cluster sampling technique. Total carbon stock in the forests of the province was estimated at 144.71 million tons with an average of 127.66 ± 9.32 t/ha. Aboveground carbon stock was 68.15 million tons accounting for 48% of the total forest carbon stock of the province. Further, belowground biomass and litter accounted for 10% and 1% respectively. The mean aboveground carbon stock was 59.98 ± 4.26 t/ha. The highest aboveground carbon stock was found in dry temperate forests (99.41 t/ha) followed by moist temperate (85.04 t/ha). Overall, temperate forests have aboveground carbon stock of 90.52 t/ha. Temperate and subtropical forests of Pakistan with high carbon densities have ample potential for reducing forest sector emissions. Therefore, forests of Khyber Pakhtunkhwa province having substantial carbon stocks must be conserved for climate change mitigation. Present study provides a framework for carbon stock assessments in other temperate and subtropical regions of the world. | 10.1007/s10661-020-8157-x |
pubmed_213_3225 | Acute murine infection with T. cruzi results in polyclonal lymphocyte responses manifested by blast transformation of a large fraction of B, CD4+, and CD8+ cells. We describe here the finding of significant increases in the splenic representation of minor populations, Ly-1 + B cells and CD4-CD8- T cells. These lymphocyte populations might play an important role in the host response, as shown by T. cruzi infection of hosts that had been lethally irradiated and reconstituted with autologous bone marrow. Under these conditions, the splenic polyclonal PFC responses are nearly abrogated, and not restored by the transfer of syngeneic peritoneal cells which, however, reconstitute T15 idiotype production in the same hosts. Control levels of PFC responses, however, are reconstituted by transfer of syngeneic splenic T cells. Since bone marrow-reconstituted animals contain normal numbers of CD4+ and CD8+ T cells which are actually activated by infection, these results suggest the participation of other T cell populations in the host response to infection, as also suggested by the marked increases in T cell receptor gamma and delta messages detected in the spleen of infected animals. The implications of these findings in immunopathology of Chagas' disease are discussed. | 10.1093/intimm/1.2.176 |
pubmed_781_11920 | Protein nanoparticles are often not very stable in a complex food matrix because they are primarily stabilized by electrostatic repulsion. In this study, we envisaged the stabilization of zein nanoparticles through Maillard conjugation reactions with polysaccharides of different molecular mass. Zein nanoparticles (0.5% w/v) containing resveratrol (0.025% w/v grape skin extract) were produced by liquid antisolvent precipitation and coated with Maillard conjugates (MC) of sodium caseinate and different molecular mass carbohydrates during particle production. Zein nanoparticles coated with conjugated polysaccharides of 2.8, 37, and 150 kDa had diameters of 198 ± 5, 176 ± 6, and 180 ± 3 nm, respectively. The encapsulation efficiency (∼83%) was not affected by conjugation, but the conjugates significantly improved particle stability against changes in pH (2.0-9.0), CaCl2 addition (up to 100 mM), and heat treatment (30-90 °C, 30 min). Zein nanoparticles coated by MC may therefore be suitable delivery systems for hydrophobic bioactive molecules in a wide range of commercial products. | 10.1021/acs.jafc.5b02699 |
pubmed_897_11638 | Anterior cruciate ligament (ACL) injuries affect more than 175,000 patients annually. Located in the center of the knee joint, the ACL is the major stabilizing ligament of the knee. If the ACL is injured, then the knee becomes unstable and can buckle when the person pivots. Surgeons can use autograft or allograft tissue to accomplish ACL reconstruction by using a single-bundle or double-bundle type of repair. The surgeon performs the reconstruction arthroscopically, using two ports and a small incision over the anteromedial surface of the tibia to facilitate passage of the graft and for distal fixation of the graft. Correct placement of the tibial and femoral tunnels is the most important technical aspect of the procedure. After reconstruction, the patient must undergo intense physical therapy starting one or two days after surgery. If diligent with physical therapy, then the patient can return to full activity as soon as four months after surgery. | 10.1016/j.aorn.2010.08.021 |
pubmed_49_10857 | SS-A/Ro is a nucleocytoplasmic ribonucleoprotein (RNP) particle that is a common target of autoimmune response in Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE). Previously, SS-A/Ro has been shown to be composed of at least two polypeptide antigens of 60 and 52 kD noncovalently associated with a set of small RNAs, designated Y1-Y5. A serum from an SS patient was selected to screen a lambda gt11 cDNA library constructed from human T cell lymphoblastic leukemia (MOLT-4) mRNA. An immunoreactive clone was isolated that possessed a 1.8-kb cDNA insert. In vitro transcription and translation of the cDNA resulted in the synthesis of a 57.5-kD polypeptide which was specifically immunoprecipitated by SS-A/Ro antisera. The identity of the cDNA encoded protein as the 60-kD SS-A/Ro antigen was established by proteolytic peptide mapping of the cDNA-encoded protein and the 60-kD HeLa cell antigen. The sequence of the cDNA shows that the 60-kD SS-A/Ro protein possesses both RNA binding protein consensus sequences and a single zinc-finger motif. Recombinant SS-A/Ro antigen produced in bacteria proved to be a sensitive and specific reagent for detection of anti-SS-A/Ro antibodies in patient sera. The availability of the 60-kD SS-A/Ro cDNA will enable detailed analysis of the molecular structure and function of the SS-A/Ro RNP particle and its role in autoimmune pathology. | 10.1172/JCI114013 |
pubmed_278_22971 | BACKGROUNDS
Between 2009 and 2018, the number of opioid-related deaths (ORDs) in Scotland showed a dramatic increase, whereas in England and Wales, a much lower increase in ORD was seen. This regional difference is remarkable, and the situation in Scotland is worrisome. Therefore, it is important to identify the drivers of ORD in Scotland.
METHODS
A systematic literature review according to PRISMA guidelines was conducted to identify peer-reviewed studies about key drivers for the observed differences in ORDs between Scotland and England/Wales. In addition, non-peer-reviewed reports on nationwide statistical data were retrieved via Google and Google Scholar and analysed to quantify differences in ORD drivers between Scotland and England/Wales.
RESULTS
The systematic review identified some important drivers of ORD, but none of these studies provided direct or indirect comparisons of ORD drivers in Scotland and England/Wales. However, the reports with nationwide statistical data showed important differences in ORD drivers between Scotland and England/Wales, including a higher prevalence of people using opioids in a problematic way (PUOP), more polydrug use in people using drugs in a problematic way (PUDP), a higher age of PUDP, and lower treatment coverage and efficacy of PUDP in Scotland compared to England/Wales, but no regional differences in injecting drug use, incarceration/prison release without treatment, and social deprivation in PUDP.
CONCLUSION
It is concluded that the opioid crisis in Scotland is best explained by a combination of drivers, consisting of a higher population involvement in (problematic) opioid use (notably methadone), relatively more polydrug use (notably benzodiazepines and gabapentinoids), a steeper ageing of the PUOP population in the past 2 decades, and lower treatment coverage and efficacy in Scotland compared to England/Wales. The findings have important consequences for strategies to handle the opioid crisis in Scotland. | 10.1159/000516165 |
pubmed_361_10174 | Hypertension, both essential and experimental is characterised by increased vascular resistance. This is in part structural, due to increases in the wall-to-lumen ratio secondary to vascular hypertrophy; however, functional increases in responses to neurohumoral stimuli also occur. The latter may be a consequence of hypertrophy or if a selective increase is observed, an indication of a primary underlying hypertensive mechanism. In essential hypertension, enhanced responsiveness to both angiotensin II and alpha-adrenoceptor agonists are seen. However, in some experimental models, more selective increased responses have been reported. The mechanism of alpha-adrenoceptor-mediated vascular smooth muscle contraction is reviewed and the role of inositol phosphates and diacylglycerol as second messengers is discussed. The precise mechanism of increased vascular responses in hypertension is still uncertain. | pubmed_361_10174 |
pubmed_958_20563 | Historically, the treatment of advanced non-small cell lung cancer (NSCLC) with cisplatin-based therapy has been a nearly futile effort. Median survival was seldom greater than six months, and fewer than 20% of those with metastatic NSCLC survived more than one year. In addition, toxicity often equaled, if not exceeded, benefit. Over the past five years, however, we have witnessed an explosion of new agents in advanced lung carcinoma. These new agents-in particular the taxanes, gemcitabine, vinorelbine, and topoisomerase I inhibitors-have breathed new life into clinical research. The therapeutic gains, though modest, are real. Paclitaxel, to a large extent, given either alone or in combination with platinols, has led the charge. | pubmed_958_20563 |
pubmed_943_4770 | The factors influencing the oligomerization state of OXA-10 and OXA-14 class D beta-lactamases in solution have been investigated. Both enzymes were found to exist as an equilibrium mixture of a monomer and dimer, with a K(d) close to 40 microM. The dimeric form was stabilized by divalent metal cations. The ability of different metal ions to stabilize the dimer was in the following order: Cd(2+) > Cu(2+) > Zn(2+) > Co(2+) > Ni(2+) > Mn(2+) > Ca(2+) > Mg(2+). The apparent K(d)s describing the binding of Zn(2+) and Cd(2+) cations to the OXA-10 dimer were 7.8 and 5.7 microM, respectively. The metal ions had a profound effect on the thermal stability of the protein complex observed by differential scanning calorimetry. The enzyme showed a sharp transition with a T(m) of 58.7 degrees C in the absence of divalent cations, and an equally sharp transition with a T(m) of 78.4 degrees C in the presence of a saturating concentration of the divalent cation. The thermal transition observed at intermediate concentrations of divalent metal ions was rather broad and lies between these two extremes of temperature. The equilibrium between the monomer and dimer is dependent on pH, and the optimum for the formation of the dimer shifted from pH 6.0 in the absence of divalent cations to pH 7.5 at saturating concentrations. The beta-lactamase activity increased approximately 2-fold in the presence of saturating concentrations of zinc and cadmium ions. Reaction with beta-lactams caused a shift in the equilibrium toward monomer formation, and thus an apparent inactivation, but the divalent cations protected against this effect. | 10.1021/bi0025969 |
pubmed_753_10447 | A strong evidence base provides the foundation for planning and response strategies. Investments in pandemic preparedness included support for research that aided early detection, response, and control of the 2009 influenza A (H1N1) (pH1N1) pandemic. Scientific investigations conducted during the pandemic guided understanding of the virus, disease severity, and epidemiologic risk factors. Field investigations also produced information that strengthened guidance for the use of antivirals, identification of target populations for monovalent pH1N1 vaccine, and refinement of recommendations for social distancing measures. Communication of this evolving evidence base was important to sustaining credibility of public health. Areas where substantial controversy emerged, such as the optimal approach to respiratory protection of healthcare workers, often suffered from gaps in the evidence base. Many aspects of the 2009-2010 pandemic influenza experience provide ongoing opportunities for additional study, which will strengthen plans for future pandemic response as well as control of seasonal influenza. | 10.1093/cid/ciq007 |
pubmed_848_1764 | Ninety-three women married to men who had experienced major medical crises resulting from coronary heart disease responded to a mail questionnaire designed to elicit the needs directly or indirectly created for them by their husbands' disease. The three areas of need--education, prevention, and support services--selected for evaluation had not been submitted previously for assessment with this population. Responses to the questionnaire indicated strong needs in all three areas. The results of the survey have implications for intervention with families by professionals in the areas of assessment, programming, and the professional's relationship to individual members of this population. | 10.1093/hsw/15.4.291 |
pubmed_794_18465 | The abnormal biological functions of HDAC6 were closely related to the occurrence and development of various tumors, making HDAC6 gradually become promising therapeutic target for cancer treatment and inspiring researchers to explore and develop selective HDAC inhibitors. In this study, based on the classical pharmacophore model of HDAC inhibitors, 20 compounds were designed and synthesized by modifying the Cap group, and the biological activities of the target compounds were assessed through anti-proliferation and enzyme inhibition experiments. The title compounds exhibited varying degrees of inhibitory activities against the selected tumor cell lines, especially the compounds 9m, 9q, and 12c, which were further evaluated at the enzymatic level. The enzyme inhibition assay showed that compound 12c exerted broad-spectrum enzyme inhibitory activities and compounds 9m and 9q were more inclined to inhibit HDAC6, exhibiting certain selective inhibitory activities among the representative subtypes. Moreover, the binding modes of compounds 9q and 12c in HDAC1&6 were further explored via computational approaches to elucidate the molecular mechanisms underlying selective inhibitory activities, providing valuable hints for the discovery of novel HDAC6 inhibitors. | 10.1016/j.bioorg.2022.105874 |
pubmed_1063_7024 | Oligo- and polycyclosiloxanes were obtained by the polycondensation of (tetrahydroxy)(tetraaryl)cyclotetrasiloxanes in equilibrium and non-equilibrium conditions in the presence and absence of montmorillonite (MMT). Their composition and the structures of their components were investigated by infrared (IR) spectroscopy, 29Si nuclear magnetic resonance (NMR) spectroscopy, atmospheric pressure chemical ionization (APCI) mass spectrometry, powder X-ray diffraction (XRD), and gel-penetrating chromatography (GPC). Also, a comparison of polymers formed in the presence of MMT and via anionic polymerization was performed showing differences in their structures. | 10.3390/polym10040422 |
pubmed_647_22680 | This computer modelling study on motor cortex stimulation (MCS) introduced a motor cortex model, developed to calculate the imposed electrical potential field characteristics and the initial response of simple fibre models to stimulation of the precentral gyrus by an epidural electrode, as applied in the treatment of chronic, intractable pain. The model consisted of two parts: a three-dimensional volume conductor based on tissue conductivities and human anatomical data, in which the stimulation-induced potential field was computed, and myelinated nerve fibre models allowing the calculation of their response to this field. A simple afferent fibre branch and three simple efferent fibres leaving the cortex at different positions in the precentral gyrus were implemented. It was shown that the thickness of the cerebrospinal fluid (CSF) layer between the dura mater and the cortex below the stimulating electrode substantially affected the distribution of the electrical potential field in the precentral gyrus and thus the threshold stimulus for motor responses and the therapeutic stimulation amplitude. When the CSF thickness was increased from 0 to 2.5 mm, the load impedance decreased by 28%, and the stimulation amplitude increased by 6.6 V for each millimetre of CSF. Owing to the large anode-cathode distance (10 mm centre-to-centre) in MCS, the cathodal fields in mono- and bipolar stimulation were almost identical. Calculation of activating functions and fibre responses showed that only nerve fibres with a directional component parallel to the electrode surface were excitable by a cathode, whereas fibres perpendicular to the electrode surface were excitable under an anode. | 10.1007/BF02345810 |
pubmed_1022_9271 | Johne's disease is an infectious chronic inflammatory bowel disease in ruminants. The key factor for the management of this disease is an early positive diagnosis. Unfortunately, most diagnostics detect animals with Johne's disease in the clinical stage with positive serology and/or positive fecal cultures. However, for effective management of the disease within herds, it is important to detect infected animals as early as possible. This might only be possible with the help of parameters not specific for Johne's disease but that give an early indication for chronic infections such as weight development. Here we report our findings on the development of total body weight and weight gain during the first six months of goats experimentally infected to induce Johne's disease. Twenty dairy goat kids age 2 to 5 days were included in this study. Goats were divided into two groups: a negative control group and a positive infected group. The weight was obtained weekly throughout the study. Goats of the positive group were infected at the age of seven weeks. We detected significant changes in weight gain and total body weight as early as one week after infection. Differences are significant throughout the six month time period. Weight as a non-specific parameter should be used to monitor infection especially in studies on Johne's disease using the goat model. Our study suggests that goats with Johne's disease have a reduced weight gain and reduced weight when compared with healthy goats of the same age. | 10.1371/journal.pone.0084049 |
pubmed_788_16279 | Aggregates and solubilized trimers of LHCII were characterized by circular dichroism (CD), linear dichroism and time-resolved fluorescence spectroscopy and compared with thylakoid membranes in order to evaluate the native state of LHCII in vivo. It was found that the CD spectra of lamellar aggregates closely resemble those of unstacked thylakoid membranes whereas the spectra of trimers solubilized in n-dodecyl-beta,D-maltoside, n-octyl-beta,D-glucopyranoside, or Triton X-100 were drastically different in the Soret region. Thylakoid membranes or LHCII aggregates solubilized with detergent exhibited CD spectra similar to the isolated trimers. Solubilization of LHCII was accompanied by profound changes in the linear dichroism and increase in fluorescence lifetime. These data support the notion that lamellar aggregates of LHCII retain the native organization of LHCII in the thylakoid membranes. The results indicate that the supramolecular organization of LHCII, most likely due to specific trimer-trimer contacts, has significant impact on the pigment interactions in the complexes. | 10.1016/j.bbabio.2007.01.010 |
pubmed_615_6585 | White organic light-emitting devices (OLEDs) were fabricated by combining a blue OLED with a color conversion layer made of mixed Y3Al5O12:Ce3+ green and Ca2AlO19:Mn4+ red phosphors. The X-ray diffraction patterns showed that Ce3+ ions in the Y3Al5O12:Ce3+ phosphors completely substituted for the Y3+ ions and the Mn4+ ions in the CaAl12O19:Mn4+ phosphors completely substituted for the Ca2+ ions. Electroluminescence spectra at 11 V for the OLEDs fabricated utilizing a color conversion layer showed that the Commission Internationale de l'Eclairage coordinates for the Y3Al5O12:Ce3+ and CaAl12O19:Mn4+ phosphors mixed at the ratio of 1:5 and 1:10 were (0.31, 0.34) and (0.32, 0.37), respectively, indicative of a good white color. | 10.1166/jnn.2013.7003 |
pubmed_94_8658 | BACKGROUND
Human Immunodeficiency Virus (HIV) infection and low birth weight (LBW) continue to be significant public health concerns in many low-income countries including Ethiopia. Yet the effect of maternal HIV infection on birth weight has not been thoroughly explored and the existing studies reported opposing findings. We examined the association between maternal HIV infection and LBW in a tertiary hospital in Southern Ethiopia.
METHODS
A retrospective cohort study was conducted based on the medical records of 277 HIV-negative and 252 HIV-positive mothers who gave singleton live birth between September 2014 to August 2017 in Hawassa University Comprehensive Specialized Hospital, Southern Ethiopia. The recodes were identified using systematic sampling approach and relevant information were extracted by using pretested extraction form. Multivariable binary logit model was fitted to examine the relationship between the exposure and outcome while adjusting for potential confounders. Adjusted odds ratio (AOR) and 95% confidence intervals (CI) is used for summarizing the findings of the analysis.
RESULTS
The mean (± standard deviation) birth weight of infants born to HIV-negative women (3.1 ± 0.7 kg) was significantly higher than those born to HIV-positive counterparts (3.0 ± 0.6 kg) (p = 0.020). The prevalence of LBW was also significantly higher in the HIV-exposed group (22.2%) than the non-exposed group (13.7%) (p = 0.011). In the logit model adjusted for multiple covariates, HIV-positive women had four times increased odds than HIV-negative women to give birth to LBW infant(AOR = 4.03, 95% CI: 2.01-8.06). Other significant predictors of LBW were rural place of residence (AOR = 2.04, 95% CI: 1.16-3.60), prenatal anemia (AOR = 3.17, 95% CI: 1.71-5.90), chronic hypertension (AOR = 3.68, 95% CI: 1.10-12.46) and preeclampsia (AOR = 6.80, 95% CI: 3.00-15.38).
CONCLUSION
Maternal HIV infection is associated with increased odds of LBW. HIV prevention activities are also likely to contribute for the reduction of LBW. | 10.1186/s13052-020-00834-3 |
pubmed_58_1506 | BACKGROUND
Gold mines represent a potential hotspot for Mycobacterium tuberculosis (Mtb) transmission and may be exacerbating the tuberculosis (TB) epidemic in South Africa. However, the presence of multiple factors complicates estimation of the mining contribution to the TB burden in South Africa.
METHODS
We developed two models of TB in South Africa, a static risk model and an individual-based model that accounts for longer-term trends. Both models account for four populations - mine workers, peri-mining residents, labor-sending residents, and other residents of South Africa - including the size and prevalence of latent TB infection, active TB, and HIV of each population and mixing between populations. We calibrated to mine- and country-level data and used the static model to estimate force of infection (FOI) and new infections attributable to local residents in each community compared to other residents. Using the individual-based model, we simulated a counterfactual scenario to estimate the fraction of overall TB incidence in South Africa attributable to recent transmission in mines.
RESULTS
We estimated that the majority of FOI in each community is attributable to local residents: 93.9% (95% confidence interval 92.4-95.1%), 91.5% (91.4-91.5%), and 94.7% (94.7-94.7%) in gold mining, peri-mining, and labor-sending communities, respectively. Assuming a higher rate of Mtb transmission in mines, 4.1% (2.6-5.8%), 5.0% (4.5-5.5%), and 9.0% (8.8-9.1%) of new infections in South Africa are attributable to gold mine workers, peri-mining residents, and labor-sending residents, respectively. Therefore, mine workers with TB disease, who constitute ~ 2.5% of the prevalent TB cases in South Africa, contribute 1.62 (1.04-2.30) times as many new infections as TB cases in South Africa on average. By modeling TB on a longer time scale, we estimate 63.0% (58.5-67.7%) of incident TB disease in gold mining communities to be attributable to recent transmission, of which 92.5% (92.1-92.9%) is attributable to local transmission.
CONCLUSIONS
Gold mine workers are estimated to contribute a disproportionately large number of Mtb infections in South Africa on a per-capita basis. However, mine workers contribute only a small fraction of overall Mtb infections in South Africa. Our results suggest that curtailing transmission in mines may have limited impact at the country level, despite potentially significant impact at the mining level. | 10.1186/s12916-018-1037-3 |
pubmed_196_10850 | Determining depression symptoms in schizophrenic patients is a challenging process because of a degree of similarity between depression symptoms and negative symptoms and the extrapyramidal side effects of neuroleptic drugs, but it is crucial to evaluate and measure depression among patients with schizophrenia for a better clinical outcome. The Calgary Depression Scale for Schizophrenia (CDSS) is a valid and reliable instrument used for the evaluation of depression in schizophrenia. This study aimed to determine the psychometric properties of the Persian version of CDSS in a sample of people with schizophrenia. Clinical interviews were conducted with 95 schizophrenic patients (40 inpatients and 55 outpatients), who were assessed with the Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale (HDRS-17 and HDRS-24 items), and the Calgary Depression Rating Scale (CDSS). Then an exploratory factor analysis was conducted to determine correlations between scales, Cronbach's alpha, and cutoff scores. The factor analysis led to the extraction of a unifactorial solution. The CDSS had significant relationships with PANSS Negative and PANSS General. However, it had no significant relationship with PANSS Positive and the PANSS Total. The CDSS also had significant relationships with HDRS-17 and HDRS-24. In addition, Cronbach's alpha of total score, test-retest reliability, and cutoff score were estimated at 0.86, 0.82, and 8 (sensitivity = 0.79 and specificity = 0.84), respectively. The findings support the CDSS unifactorial approach. Results also showed that the CDSS Persian version had acceptable psychometric properties; thus, it could be employed to evaluate depression among schizophrenic patients. | 10.1016/j.ajp.2019.08.017 |
pubmed_690_756 | The acidic transcriptional activation motif functions in all eukaryotes, which suggests that it makes contact with some universal component of the transcriptional apparatus. Transcriptional activation by the yeast regulatory protein GAL4 requires an acidic region at its carboxyl terminus. Here we implement a selection scheme to determine whether GAL4 can still function when this C-terminal domain has been deleted. It can, when accompanied by a mutation in the SUG1 gene which is an essential gene in yeast. Analysis of mutant SUG1 in combination with various alleles of GAL4 indicates that SUG1 acts through a transcriptional pathway that depends on GAL4, but requires a region of GAL4 other than the C-terminal acidic activation domain. The predicted amino-acid sequence of SUG1 closely resembles that of two human proteins, TBP1 and MSS1, which modulate expression mediated by the human immunodeficiency virus tat gene. | 10.1038/357698a0 |
pubmed_826_7215 | UNLABELLED
Enhanced external counterpulsation (EECP) is a new therapy offered to patients with refractory angina pectoris (AP).
PURPOSE
To assess the effect of EECP on AP, quality of life (QoL) and exercise capacity in a design starting with a control period to avoid the influence of regression-towards-the-mean.
METHODS
Patients were examined two months before EECP, just before, just after, and three and 12 months after EECP. EECP was given for 1 h 5 days a week in 7 weeks. Three sets of pneumatic cuffs were mounted on the lower extremities and inflated sequentially in diastole to 260 mm Hg.
RESULTS
50 patients were included (male 72%, mean age: 62.5 years). Mean daily AP attacks were reduced during EECP from 2.7 to 0.9 (p < 0.005) and the Canadian Cardiovascular Society classification was reduced by at least 1 class in 82% just after EECP, 79% 3 months and 76% 12 months after EECP (p < 0.0002). Generic (SF36) and disease-specific QoL (Seattle AP questionnaire) improved just after, 3 and 12 months after compared with that before EECP. There was a significant improvement in exercise capacity and exercise-induced chest pain just after, three and 12 months after EECP (p < 0.02). No change was detected during the control period.
CONCLUSIONS
EECP improves generic and disease-specific QoL, angina intensity and exercise capacity in at least 12 months. | 10.3109/14017431.2014.994028 |
pubmed_404_156 | Cladosporium resinae was grown in submerged cultures on glucose; on Jet-A commercial aviation fuel; and on a series of n-alkanes, n-decane through n-tetradecane. Cell yield was greatest on glucose and least on Jet-A; n-alkanes were intermediate. Among n-alkanes cell yield decreased as chain length increased, except for n-dodecane, which supported less growth than n-tridecane or n-tetradecane. The total fatty acids of stationary-phase cells were analyzed by gas-liquid chromatography. In all cases the predominant fatty acids were 16:0, 18:1, and 18:2. The fatty acid composition of glucose-grown cells was similar to that of hydrocarbon-grown cells. Cells grown on n-tridecane or n-tetradecane yielded small amounts of acids homologous to the carbon source, but a similar correlation was not noted for n-decane, n-undecane, or n-dodecane. Cells grown on n-undecane or n-tridecane contained more odd-carbon fatty acids than cells grown on the other substrates, and the effect was more pronounced in n-tridecane-grown cells. Thus, the fatty acids of this organism are derived chiefly from de novo synthesis rather than from direct incorporation of oxidized hydrocarbons. The extent of direct incorporation increases as the chain length of the hydrocarbon growth substrate is increased. | 10.1128/jb.108.2.777-781.1971 |
pubmed_511_13556 | BACKGROUND
Behcet disease (BD) is a worldwide-occurred autoimmune disorder and currently lack of optional successful treatment. An ancient traditional Chinese medical formula called Glycyrrhizae Decoction for Purging Stomach-Fire (GDPSF) was recorded and nowadays has been observed to be effective for BD patients. However, the strict randomized controlled and double-blinding trail is needed to further assess this alternative medicine.
METHODS
To ascertain the potential effects and safety of GDPSF for BD patients and to determine whether combination application of GDPSF and thalidomide could possibly reduce the side effects and increase effectiveness for BD management, we will conduct a randomized, double blind, controlled clinical trial. Patients enrolled will be randomly assigned into 3 groups: GDPSF group, thalidomide group, and integrative group (treated by both GDPSF and thalidomide). Participants will receive treatment for 6 months and accept a 12 months follow-up. Before and after treatment, clinical manifestations, blood tests, thalidomide dosage, remission levels, quality of life, and satisfactory levels will be assessed. The data of assessments on each group before and after treatments will be collected and analyzed through historical control, while between groups through intergroup control. Then statistical analysis will be applied to assess the effects and safety.
DISCUSSION
This study protocol will assess the effects and safety of GDPSF for BD patients GDPSF. Combination application of GDPSF and thalidomide might be a new integrative medical method for BD patients.
TRIAL REGISTRATION
Chinese Clinical Registry (ChiCTR-ONC-16009621) on Oct. 2016 http://www.chictr.org.cn/showproj.aspx?proj=16395. | 10.1097/MD.0000000000010265 |
pubmed_486_14656 | Incorporation of electron-deficient N-protonated 2,4,6-tri(4-pyridyl)-1,3,5-triazine (H3TPT) into electron-rich chlorocadmate leads to a novel organic-inorganic hybrid [H3TPT]2[Cd3Cl12] (1), which features as a trinuclear anionic cluster [Cd3Cl12]6- with one CdCl6 octahedron and two CdCl4 tetrahedra via edge-sharing mode and exhibits excellent photochromic performance with fast photoresponsive rate, obvious coloration contrast and high thermal stability. | 10.1039/c9dt03494c |
pubmed_500_2538 | Currently the concept of quality of life is being discovered, analyzed and adequately defined for the field of surgery. The objective finding is being supplemented by a higher measure of subjective assessment. The aim is to intensify the individual side of the dialogue in order to achieve an approximately symmetrical partnership. As in the 19th century the faculty of medicine, including surgery, still understands itself as psychosomatic medicine; at the same time it has competency in the natural and humanistic sciences. The concept of quality of life adds useful and above all comparable parameters. | pubmed_500_2538 |
pubmed_334_3256 | The marathon poses a considerable physical challenge for athletes of all levels. When combined with high heat and humidity, not only is performance potentially compromised, but health and well-being are also at risk. There are well recognised effects of heat and hydration status on the cardiovascular and thermoregulatory systems that can account for the decreased performance and increased sensation of effort that are experienced when competing in the heat. Elevated exercise heart rate and core temperature at the same absolute exercise intensity are commonly reported. Dehydration occurring during exercise in the heat and results in reductions in stroke volume, cardiac output and blood pressure, as well as a marked decline in blood flow to the working muscles. Recent work suggests that hyperthermia may have a direct affect on the CNS and the brain may contribute to fatigue during prolonged exercise in a warm environment. At present, evidence supports a significant role of catecholaminergic neurotransmission, but there are a number of metabolic and circulatory perturbations occurring within the brain that may also be important in the fatigue process. | 10.2165/00007256-200737040-00032 |
pubmed_313_10005 | Adenoid cystic carcinoma of the breast (breast-ACC) is a rare and indolent tumor with a good prognosis despite its triple-negative status. However, we observed different outcomes in the present study. Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we enrolled a total of 89,937 eligible patients with an estimated 86 breast-ACC cases and 89,851 invasive ductal carcinoma (IDC) patients. In our study, breast-ACC among women presented with a higher proportion of triple-negative breast cancer (TNBC), which was more likely to feature well-differentiated tumors, rare regional lymph node involvement and greater application of breast-conserving surgery (BCS). Kaplan-Meier analysis revealed that patients with breast-ACC and breast-IDC patients had similar breast cancer-specific survival (BCSS) and overall survival (OS). Moreover, using the propensity score matching method, no significant difference in survival was observed in matched pairs of breast-ACC and breast-IDC patients. Additionally, BCSS and OS did not differ significantly between TNBC-ACC and TNBC-IDC after matching patients for age, tumor size, and nodal status. Further subgroup analysis of molecular subtype indicated improved survival in breast-ACC patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/Her2-) tumors compared to IDC patients with HR+/Her2- tumors. However, the survival of ACC-TNBC and IDC-TNBC patients was similar. In conclusion, ACCs have an indolent clinical course and result in similar outcomes compared to IDC. Understanding these clinical characteristics and outcomes will endow doctors with evidence to provide the same intensive treatment for ACC-TNBC as for IDC-TNBC and lead to more individualized and tailored therapies for breast-ACC patients. | 10.18632/oncotarget.14052 |
pubmed_926_16934 | Numerically exact nonadiabatic eigenfunctions are computed for a two-dimensional conical intersection with circular symmetry, for which a pseudorotation quantum number is conserved and all eigenstates are doubly degenerate. In the calculations reported here, the conical intersection is submerged, with energy below the zero point level. The complete real-valued vibrational-electronic eigenfunctions are visualized using Hunter's exact factorization for the total vibrational amplitude factor and color for the electronic factor. The zero-point levels have nonzero amplitude at the conical intersection. Nodes in the degenerate nonadiabatic eigenfunctions are classified as accidental if they can be moved or removed by a change in degenerate basis and as essential if they cannot. An integer electronic index defines the order of the nodes for nonadiabatic eigenfunctions by simple closed counterclockwise line integrals. Higher eigenstates can have accidental conical nodes around the conical intersection and essential nodes of varying circular orders at the conical intersection. The signs of the essential nodes are all opposite the sign of the conical intersection and the signed node orders obey sum rules. Even for submerged conical intersections, the appearance of the exact eigenstates motivates use of signed, half-odd-integral, pseudorotation quantum numbers j. Essential nodes of absolute order (|j| - 1/2) are located on the conical intersection for |j| greater than or equal to 3/2. The eigenfunctions around essential first order nodes are right circular cones with their vertex at the conical intersection. | 10.1021/acs.jpca.7b07140 |
pubmed_536_24221 | Fibrin is a hydrogel carrier widely used in cartilage tissue engineering. It is rapidly degraded by plasmin, which is produced by the cells. epsilon-Aminocaproic acid (EACA) can be used to inhibit this enzyme and thus save the fibrin carrier. In this study we investigated the effect of EACA on the transforming growth factor beta-1-induced chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells (hMSCs). To assess this, we used the standard pellet culture system, and EACA treatment was compared to an untreated chondrogenic control. To investigate differentiation, real-time RT-PCR was used on chondrocytic marker genes: aggrecan, collagen types II and X, and the SRY-related HMG-box gene 9 (SOX9). Also, specific glycosaminoglycan production was measured. Safranin-O/fast green staining was used to localize proteoglycans and collagens within the pellet. All results concur that EACA did not affect the chondrogenic differentiation process at 5 muM concentration, which is adequate to inhibit fibrin degradation. Therefore, it is a useful plasmin inhibitor for cartilage tissue engineering with hMSCs. | 10.1089/ten.tea.2008.0400 |
pubmed_436_15250 | OBJECTIVES/HYPOTHESIS
The present study is a long-term follow-up of speech perception outcomes and cochlear implant use in three cases of meningitis that occurred after cochlear implantation.
STUDY DESIGN
Case series study.
METHODS
Study was performed on three children implanted with different models of Clarion devices, two of them with positioner. Recognition and comprehension were assessed via the Italian adaptation of GASP (TAP) test, and phonetically balanced bi-syllabic words in open-set. High resolution computed tomography scan acquisition was performed to obtain axial coronal and oblique multiplanar reconstructions of the cochlea.
RESULTS
Two patients were affected by enlarged cochlear acqueduct and Mondini malformation the first carrying positioner. One patient had a normal cochlea, and the positioner could have been the main cause of bacterial spread. As a consequence of meningitis the child with normal cochlea and the other with enlarged vestibular acqueduct developed cochlear ossification, increased M-level and worsening of hearing outcomes. The child with Mondini malformation developed facial nerve stimulation. Contralateral implantation was performed in the first two patients.
CONCLUSION
Bacterial meningitis occurring after cochlear implantation may induce cochlear ossification, facial nerve stimulation, and permanent or temporary loss of implant use. Planned follow-up with high resolution computed tomography and evaluation of M-levels could be useful prognostic tools in the management of these patients. | 10.1097/MLG.0b013e3181758154 |
pubmed_482_21988 | Three-dimensional (3D) wearable piezoresistive sensors with excellent performance are urgently needed in many emerging fields. Herein, a hybrid piezoresistive sensor with 3D structure, which is framed by loofah sponge and coated with reduced graphene oxide modified with carbon black nanoparticles (rGO-CB@LS), was obtained via a facile solvothermal method. The ingenious use of loofah sponge (LS) provides a 3D highly ordered structure with excellent flexibility for the hybrid sensor, which assists the sensor free from the dependence on an organic substrate and eliminates the pollution to the environment. While the addition of carbon black (CB) nanoparticles can reduce the contact resistance between rGO sheets, improve the conductivity and sensitivity effectively, and shorten the response/recovery time of the sensor. An ultralight piezoresistive sensor, which is low cost and environmentally friendly, was obtained under the synergy of LS and rGO-CB, accompanied by high sensitivity and good stability. This novel sensor also exhibits excellent performance in detecting tiny and big human activities, demonstrating its great potential for a new generation of 3D wearable sensors. | 10.1021/acsami.0c09813 |
pubmed_368_24148 | Neurophysiological and functional imaging studies have investigated the representation of animate and inanimate stimulus classes in monkey inferior temporal (IT) and human occipito-temporal cortex (OTC). These studies proposed a distributed representation of stimulus categories across IT and OTC and at the same time highlighted category specific modules for the processing of bodies, faces and objects. Here, we investigated whether the stimulus representation within the extrastriate (EBA) and the fusiform (FBA) body areas differed from the representation across OTC. To address this question, we performed an event-related fMRI experiment, evaluating the pattern of activation elicited by 200 individual stimuli that had already been extensively tested in our earlier monkey imaging and single cell studies (Popivanov et al., 2012, 2014). The set contained achromatic images of headless monkey and human bodies, two sets of man-made objects, monkey and human faces, four-legged mammals, birds, fruits, and sculptures. The fMRI response patterns within EBA and FBA primarily distinguished bodies from non-body stimuli, with subtle differences between the areas. However, despite responding on average stronger to bodies than to other categories, classification performance for preferred and non-preferred categories was comparable. OTC primarily distinguished animate from inanimate stimuli. However, cluster analysis revealed a much more fine-grained representation with several homogeneous clusters consisting entirely of stimuli of individual categories. Overall, our data suggest that category representation varies with location within OTC. Nevertheless, body modules contain information to discriminate also non-preferred stimuli and show an increasing specificity in a posterior to anterior gradient. | pubmed_368_24148 |
pubmed_424_8146 | PURPOSE
To report the result of intravitreal triamcinolone acetonide in the treatment of sympathetic ophthalmia.
METHODS
A 29-year-old woman who suffered from sympathetic ophthalmia and who was being treated with systemic corticosteroid therapy received an intravitreal injection of 4 mg of triamcinolone acetonide.
RESULTS
By the 15th day after injection visual acuity had improved from 20/200 to 20/40 and serous retinal detachment had almost completely resorbed. Systemic corticosteroid therapy was reduced sequentially. By the third month after injection, the patient was in clinical remission. Her visual acuity was 20/20 and no serous detachment was observed.
CONCLUSIONS
In this study, short-term improvement in the clinical picture of a patient with sympathetic ophthalmia after intravitreal triamcinolone acetonide injection was described. The results suggest that intravitreal triamcinolone acetonide injection may be an additional tool in the treatment of sympathetic ophthalmia. | 10.1007/s00417-004-1064-y |
pubmed_1073_3886 | Breast cancers (BCs) typically express estrogen receptors (ERs) but frequently exhibit de novo or acquired resistance to hormonal therapies. Here, we show that short-term treatment with the anti-estrogens tamoxifen or fulvestrant decrease cell proliferation but increase BC stem cell (BCSC) activity through JAG1-NOTCH4 receptor activation both in patient-derived samples and xenograft (PDX) tumors. In support of this mechanism, we demonstrate that high ALDH1 predicts resistance in women treated with tamoxifen and that a NOTCH4/HES/HEY gene signature predicts for a poor response/prognosis in 2 ER+ patient cohorts. Targeting of NOTCH4 reverses the increase in Notch and BCSC activity induced by anti-estrogens. Importantly, in PDX tumors with acquired tamoxifen resistance, NOTCH4 inhibition reduced BCSC activity. Thus, we establish that BCSC and NOTCH4 activities predict both de novo and acquired tamoxifen resistance and that combining endocrine therapy with targeting JAG1-NOTCH4 overcomes resistance in human breast cancers. | pubmed_1073_3886 |
pubmed_785_11785 | BACKGROUND
Sleep disorders (SD), including apnea and nonapnea, and burning mouth syndrome (BMS) have been mutually associated with systemic diseases. Based on our research, the association between BMS and SD has not been elucidated. We determined whether SD patients have an increased risk of BMS.
METHODS
We used information from health insurance claims obtained from the Taiwanese National Health Insurance (NHI) program. We identified patients newly diagnosed with sleep apnea syndrome between 1998 and 2001 as the apnea SD cohort, and newly diagnosed patients with nonapnea SD as the nonapnea SD cohort. The non-SD cohort was 1:2 frequency matched the case group according to sex, age, and index year. We analyzed the risks of BMS by using Cox proportional hazards regression models.
RESULTS
Compared with the non-SD cohort, both of the apnea SD (adjusted HR = 2.56, 95% CI = 1.30-5.05) and nonapnea SD (adjusted HR = 2.89, 95% CI = 2.51-3.34) were associated with a significantly higher risk of BMS. The hazard ratio (HR) increased with increased age in the apnea SD cohort and in the nonapnea SD cohort compared with patients younger than 40 years of age. Female apnea SD patients (IRR = 4.63, 95% CI = 3.82-5.61) had a higher risk of developing BMS than did male patients (IRR = 1.76, 95% CI = 1.39-2.24).
CONCLUSIONS
Based on our research, SD might increase the risk of BMS. | pubmed_785_11785 |
pubmed_995_16983 | Purified NAD-malic enzyme from Ascaris suum is rapidly inactivated by the arginine reagent, 2,3-butanedione, and this inactivation is facilitated by 30 mM borate. Determination of the inactivation rate as a function of butanedione concentration suggests a second-order process overall, which is first order in butanedione. A second-order rate constant of 0.6 M-1 s-1 at pH 9 is obtained for the butanedione reaction. The inactivation is reversed by removal of the excess reagent upon dialysis. The enzyme is protected against inactivation by saturating amounts of malate in the presence and absence of borate. The divalent metal Mg2+ affords protection in the presence of borate but has no effect in its absence. The nucleotide reactant NAD+ has no effect on the inactivation rate in either the presence or absence of borate. A dissociation constant of 24 mM is obtained for E:malate from the decrease in the inactivation rate as a function of malate concentration. An apparent Ki of 0.5 mM is obtained for oxalate (an inhibitor competitive vs malate) from E:Mg:oxalate while no significant binding is observed for oxalate using the butanedione modified enzyme. The pH dependence of the first-order rate of inactivation by butanedione gives a pKa of 9.4 +/- 0.1 for the residue(s) modified, and this pK is increased when NAD is bound. The arginine(s) modified is implicated in the binding of malate. | 10.1016/0003-9861(87)90288-8 |
pubmed_219_20507 | Autosomal dominant tubulointerstitial kidney disease (ADTKD) refers to a group of conditions characterized by autosomal dominant inheritance, a bland urinary sediment with minimal blood and protein, pathologic changes of tubular and interstitial fibrosis, and slowly progressive chronic kidney disease. This commentary discusses recent advances in our medical knowledge of these conditions, including the recent identification of mutations in the MUC1 gene as a cause of ADTKD and changes in terminology proposed by Ekici et al. | 10.1038/ki.2014.125 |
pubmed_615_17220 | Management of pectus excavatum Congenital chest wall deformities are considered to be anomalies in chest wall growth related to excessive or insufficient growth (aplasia or dysplasia) of the osseous or cartilaginous structures or the rib cage. These deformities are associated in 95% to overgrowth leading into depression (pectus excavatum) or protuberance of the sternum (pectus carinatum). Pectus excavatum may lead to cardiopulmonary disorder or impact on patient's self-esteem. The management of pectus excavatum has evolved this last decade with minimal invasive repair. | pubmed_615_17220 |
pubmed_825_10877 | The study groups comprised 61 pregnant women whose gestational age ranged from 7 to 12 weeks from the last menstrual period. All patients apparently had a normal developing pregnancy; there were no clinical symptoms of pathology e.g. bleeding in early pregnancy. Eighty-two patients with a clinically and ultrasonographically normal pregnancy whose gestational age ranged from 7 to 12 weeks, served as a control group. When the anatomical position of investigated area have been obtained clearly, pulsed wave Doppler sample volume was placed on the structures of interest: the both uterine arteries and intervillous space. There is no statistically significant difference between the Resistance Index (RI) in the left or right uterine artery (P greater than 0.01) and among investigated groups of patients (P greater than 0.01). The intervillous blood flow RI in the case of molar pregnancy was 0.38 with SD +/- 0.03; in blighted ovum 0.43 with SD +/- 0.03, and in missed abortion 0.43 with SD +/- 0.02. It should be stressed that in nine (31%) cases of blighted ova and in five (26%) cases of missed abortion, intervillous space flow could not be detected. In the control group, intervillous blood flow was always visualized and the mean RI was 0.45 with SD - 0.04. Statistical analysis showed significantly higher RI in control group in comparison with other groups of patients (P less than 0.01), and significantly lower RI in molar pregnancy in comparison with other groups of patients (P less than 0.01). There was no difference in RI between blighted ova and missed abortions (P greater than 0.01). | 10.1515/jpme.1991.19.3.155 |
pubmed_712_10710 | Gallium was administered subcutaneously to mice, and was found to be localized essentially in the skeleton. It was measured in the bones of animals given daily injections of gallium sulfate. There was little or no mortality. The amount of gallium found rose with the number of injections, and was greater when higher doses were injected. Elimination was very low after cessation of treatment. Results were used to study the action of gallium on cutaneous allografts in mice. | pubmed_712_10710 |
pubmed_177_13928 | Sexually transmitted viruses infect the genital and colorectal mucosa of the partner exposed to contaminated genital secretions through a wide range of mechanisms, dictated in part by the organization of the mucosa. Because understanding the modes of entry into the organism of viruses transmitted through sexual intercourse is a necessary prerequisite to the design of treatments to block those infections, in vitro modeling of the transmission is essential. The aim of this review is to present the models and methodologies available for the in vitro study of the interactions between viruses and mucosal tissue and for the preclinical evaluation of antiviral compounds, and to point out their advantages and limitations according to the question being studied. | 10.1016/j.virol.2017.11.023 |
pubmed_6_17431 | Intrauterine growth restriction (IUGR) of the fetus, resulting from placental insufficiency (PI), is characterized by low fetal oxygen and nutrient concentrations that stunt growth rates of metabolic organs. Numerous animal models of IUGR recapitulate pathophysiological conditions found in human fetuses with IUGR. These models provide insight into metabolic dysfunction in skeletal muscle and liver. For example, cellular energy production and metabolic rate are decreased in the skeletal muscle and liver of IUGR fetuses. These metabolic adaptations demonstrate that fundamental processes in mitochondria, such as substrate utilization and oxidative phosphorylation, are tempered in response to low oxygen and nutrient availability. As a central metabolic organelle, mitochondria coordinate cellular metabolism by coupling oxygen consumption to substrate utilization in concert with tissue energy demand and accretion. In IUGR fetuses, reducing mitochondrial metabolic capacity in response to nutrient restriction is advantageous to ensure fetal survival. If permanent, however, these adaptations may predispose IUGR fetuses toward metabolic diseases throughout life. Furthermore, these mitochondrial defects may underscore developmental programming that results in the sequela of metabolic pathologies. In this review, we examine how reduced nutrient availability in IUGR fetuses impacts skeletal muscle and liver substrate catabolism, and discuss how enzymatic processes governing mitochondrial function, such as the tricarboxylic acid cycle and electron transport chain, are regulated. Understanding how deficiencies in oxygen and substrate metabolism in response to placental restriction regulate skeletal muscle and liver metabolism is essential given the importance of these tissues in the development of later lifer metabolic dysfunction. | 10.3389/fendo.2021.612888 |
pubmed_128_16175 | Maximum bladder volume could be a simple surrogate measure to screen for detrusor overactivity (DO) which manifests with a frequency and small volume voids. Urodynamic traces from 577 women were reviewed. Maximum bladder volume was obtained from bladder diary. The urodynamic traces were reviewed for data and were categorised as normal, urodynamic stress incontinence, mixed incontinence and DO. The urodynamic data and maximum voided volume were compared between different categories and Receiver operating characteristic (ROC) curves were constructed. The median value for maximum-voided volume for women with DO was not significantly different from the other categories, whereas significant differences were found for the median values for urodynamic variables. ROC curves demonstrated extremely poor sensitivity and specificity for recorded maximum bladder volume and for urodynamic variables. The maximum-voided volume recorded on a three-day bladder diary is not discriminatory as a screening test for DO. | 10.3109/01443615.2014.896886 |
pubmed_503_8541 | The evolutionarily conserved Notch-mediated intercellular signaling pathway is essential for proper embryonic development of many tissues and organs. Recent data suggest that Notch receptors and their membrane-bound ligands Delta and Serrate are involved in both patterning and cell fate determination during odontogenesis. It remains, however, uncertain if Notch signaling is important for tooth homeostasis and regeneration. Here we report on the expression of Notch receptors and the Delta1 ligand in dental pulp of normal and injured adult rat teeth. Notch receptors were absent from normal adult dental tissues, whereas expression was upregulated after injury. In injured teeth, Notch2 was expressed in mesenchymal cells of the pulp both close to the site of injury (i.e., in the dental crown) and at a distance from it (i.e., in the dental roots), Notch3 expression was mainly associated with vascular structures, while Notch1 expression was restricted to few pulpal cells close to the lesion. None of them was expressed in odontoblasts. Expression of Delta1 was upregulated in odontoblasts of the injured teeth, as well as in vascular structures. These results demonstrate the reactivation of the Notch signaling pathway during wound healing and, furthermore, highlight the similarity between developmental and regenerative processes. | 10.1006/excr.1998.4285 |
pubmed_249_5659 | A proper measurement of splanchnic metabolism involves sampling blood from the hepatic vein without backflow contamination of blood from the caval vein. We have investigated the potential problem of caval backflow in human volunteers with an indwelling hepatic vein catheter by sampling blood with different amounts of suction on the syringe (ie, sampling speeds). We also investigated the potential problem in pigs in which a balloon catheter was inserted in the hepatic vein. Pure hepatic vein samples were obtained with the balloon inflated and compared with samples obtained from the same catheter in the conventional manner. In overnight fasted humans, drawing blood samples from the hepatic vein with minimal suction ("slow" drawing) resulted in glucose values 9.6% higher than drawing the samples with greater suction ("fast" drawing). The calculated arterial-venous balance across the splanchnic bed was 4.8 times greater with "slow" blood drawing as compared with "fast" drawing. Values obtained from the pigs showed no concentration differences between pure hepatic vein samples and "slow" drawing from the hepatic vein. The current study indicates that it is possible to obtain a "true" hepatic vein sample, but backflow from the caval vein is a potential pitfall that can have a physiologically significant impact on calculated balance data. | 10.1053/meta.2001.20167 |
pubmed_272_21737 | One of the most widely recognized effects of thyroid hormones (TH) in adult mammals is their influence over energy metabolism. In the past, this has received much attention but, possibly because of the complex mode of action of thyroid hormones, no universally accepted mechanism to explain this effect has been put forward so far. Significant advances in our understanding of the biochemical processes involved in the actions of TH have been made in the last three decades and now it seems clear that TH can act through both nuclear-mediated and extranuclear-mediated pathways. TH increase energy expenditure, partly by reducing metabolic efficiency, with control of specific genes at the transcriptional level, being is thought to be the major molecular mechanism. However, both the number and the identity of the thyroid-hormone-controlled genes remain unknown, as do their relative contributions. The recent discovery of uncoupling proteins (UCPs) (in addition to UCP1 in brown adipose tissue) in almost all tissues in animals, including humans, has opened new perspectives on the understanding of the mechanisms involved in the regulation of energy metabolism by thyroid hormones. Other approaches have included the various attempts made to attribute changes in respiratory activity to a direct influence of thyroid hormones over the mitochondrial energy-transduction apparatus. In addition, an increasing number of studies has revealed that TH active in the regulation of energy metabolism include not only T3, but also other iodothyronines present in the biological fluids, such as 3,5-diiodothyronine (3,5-T2). This, in turn, may make it possible to explain some of the effects exerted by TH on energy metabolism that cannot easily be attributed to T3. | 10.1007/BF03343949 |
pubmed_742_1271 | The solid-sate structures of the two uranyl peroxides studtite, [UO2(η(2)-O2)(H2O)2]·2H2O, and metastudtite [UO2(η(2)-O2)(H2O)2] have been determined by U-L3 edge extended X-ray absorption fine structure (EXAFS) spectroscopy and show that upon removal of the interstitial water in studtite there are structural changes with a small shortening of the U-O(peroxo) and small lengthening of the U-O(yl) bonds. High-energy resolution X-Ray absorption near edge structure (HR-XANES) spectroscopy has been used to probe the differences in the local electronic structure and, supported by ab initio FEFF9.5.1 calculations, dehydration causes a shift to higher energies of the occupied O p-DOS and U d- and f-DOS of metastudtite. The HR-XANES spectrum of schoepite, [(UO2)4O(OH)6]·6H2O, has been measured as the White Line intensity can give information on the mixing of metal and ligand atomic orbitals. There is an indication for higher degree of ionicity for the U-OH bond in schoepite compared to the U-O2 bond in studtite. | 10.1039/c3dt52437j |
pubmed_24_255 | The cell wall of human fungal pathogen Aspergillus fumigatus protects the fungus against threats from environment and interacts with the host immune system. Alpha(1-3)glucan is the major polysaccharide of Aspergillus fumigatus cell wall, and it has been shown to contribute to the virulence of diverse fungal pathogens. In A. fumigatus, three putative alpha(1-3)glucan synthase genes AGS1, AGS2 and AGS3 have been identified. AGS1 is responsible for cell wall alpha(1-3)glucan biosynthesis, but strains with deletions of either AGS1 or AGS2 are not defective in virulence [Beauvais, A., Maubon, D., Park, S., Morelle, W., Tanguy, M., Huerre, M., Perlin, D.S., Latgé, J. P., 2005. Two alpha(1-3) glucan synthases with different functions in Aspergillus fumigatus. Appl. Environ. Microbiol. 71, 1531-1538]. In contrast, we present evidence that AGS3 is also responsible for cell wall alpha(1-3)glucan biosynthesis and can modulate the virulence of A. fumigatus. An AGS3 deletion strain was found to produce faster and more robust disease than the parental strain in an experimental mouse model of aspergillosis. The apparent hyper-virulence in the AGS3-deleted mutant was correlated with an increased melanin content of the conidial cell wall, a better resistance to reactive oxygen species and a quicker germination rate. These results suggest an indirect role for AGS3 in virulence through an adaptive mechanism. | 10.1016/j.fgb.2006.01.006 |
pubmed_284_877 | From a population of 130 boys between 7 and 14 years of age who had been clinically diagnosed as aggressive, hyperactive, or withdrawn, 32, 31, and 32 Ss, respectively, were randomly selected. All Ss were rated on the Behavior Problem Checklist (BPC) and the Devereux Elementary School Behavior rating scales (DESB) during the 1971-72 academic year. A descriptive intercorrelation matrix was generated for the 4 BPC scales and the 14 DESB scales. Three stepwise discriminant analyses were run: (a) BPC scales only, (b) DESB scales only, and (c) BPC and DESB scales combined. In terms of statistical and practical considerations, the four BPC subscales by themselves attained the optimal predictive accuracy (65%, or 62 of 95 children correctly identified). | 10.1007/BF00916033 |
pubmed_2_10432 | OBJECTIVES
The transcription factor SOX2 (3q26.3-q27) is an embryonic stem cell factor contributing to the induction of pluripotency in terminally differentiated somatic cells. Recently, amplification of the SOX2 gene locus has been described in squamous cell carcinoma (SCC) of different organ sites. Aim of this study was to investigate amplification and expression status of SOX2 in sinonasal carcinomas and to correlate the results with clinico-pathological data.
MATERIALS AND METHODS
A total of 119 primary tumor samples from the sinonasal region were assessed by fluorescence in-situ hybridization and immunohistochemistry for SOX2 gene amplification and protein expression, respectively. Of these, 59 were SSCs, 18 sinonasal undifferentiated carcinomas (SNUC), 10 carcinomas associated with an inverted papilloma (INVC), 19 adenocarcinomas (AD) and 13 adenoid cystic carcinomas (ACC).
RESULTS
SOX2 amplifications were found in subsets of SCCs (37.5%), SNUCs (35.3%), INVCs (37.5%) and ADs (8.3%) but not in ACCs. SOX2 amplification resulted in increased protein expression. Patients with SOX2-amplified sinonasal carcinomas showed a significantly higher rate of tumor recurrences than SOX2 non-amplified tumors.
CONCLUSION
This is the first study assessing SOX2 amplification and expression in a large cohort of sinonasal carcinomas. As opposed to AD and ACC, SOX2 amplifications were detected in more than 1/3 of all SCCs, SNUCs and INVCs. We therefore suggest that SNUCs are molecularly closely related to SCCs and INVCs and that these entities represent a subgroup of sinonasal carcinomas relying on SOX2 acquisition during oncogenesis. SOX2 amplification appears to identify sinonasal carcinomas that are more likely to relapse after primary therapy, suggesting that these patients might benefit from a more aggressive therapy regime. | 10.1371/journal.pone.0059201 |
pubmed_42_18961 | Sedum telephium L. is a medicinal plant used in antiquity to cure many types of inflammatory skin diseases. The leaves (without the external cuticle), are used to promote healing and reduce skin inflammation and pain, and contain various components. We found two major components: flavonol glycosides and polysaccharides, with molecular weight between 13,000 and 13,500 Da. We evaluated the in-vitro antioxidant and in-vivo skin photoprotective effects of three lyophilized extracts obtained from the juice of S. telephium L. leaves: a total lyophilized juice, a lyophilized flavonolic fraction, and a lyophilized polysaccharidic fraction. Two in-vitro models were used: the bleaching of the stable 2,2-diphenyl-1-picrylhydrazyl (DPPH*) radical, and the protective effect against UV-induced peroxidation on phosphatidylcholine multilamellar vesicles, as model membranes. The antioxidant/radical scavenging activity of each lyophilized extract was also assessed in-vivo by determining their ability to reduce UVB-induced skin erythema (monitored by reflectance spectrophotometry) in healthy human volunteers. The findings of the in-vitro experiments clearly demonstrated that, unlike the lyophilized polysaccharidic fraction, the lyophilized flavonolic fraction and total lyophilized juice possess strong antioxidant/free radical scavenging properties, which are likely due to phenolic compounds. Consistent with these findings, gel formulations of both the total lyophilized juice and, to a greater degree, the lyophilized flavonolic fraction appeared to possess a strong protective effect against UV-induced skin erythema in-vivo, whereas the lyophilized polysaccharidic fraction was completely ineffective. The in-vitro and in-vivo results suggest that, both the total lyophilized juice and, in particular, the lyophilized flavonolic fraction, but not the lyophilized polysaccharidic fraction of S. telephium L. leaves, have photoprotective effects against UVB-induced skin damage. | 10.1211/0022357001777261 |
pubmed_181_21239 | It is universally accepted that deep sedation involves more risks than light-to-moderate sedation. Deep sedation for endoscopic explorations is normally provided by anesthesiologists in Spain and in most countries of the European Unión. The present debate about deep sedation-anesthesia states goes beyond the topic of cardiovascular and respiratory adverse events, and targets the cognitive consequences and global increased mortality of uncontrolled sedation states, especially in specific fragile populations. We consider that strong recomendations for sedative techniques in endoscopic procedures should be made in Spain taking in consideration to two basic principles: 1) according to published evidence concerning patient safety, deep sedation must be an unequivocal responsibility of the anesthesiologist, and 2) we must define which patients are candidates for deep sedation during endoscopic procedures, as this will help to regulate patient flow in clinics and to reduce adverse effects associated with overtreatment of patients. | 10.17235/reed.2016.4471/2016 |
pubmed_987_15608 | SOX3 is critical for the development of the pituitary, brain, and face, and SOX3 mutations may lead to hypopituitarism, intellectual disability, and craniofacial abnormalities. Common SOX3 mutations are duplications and deletions of the whole or part of SOX3, yet only a few cases with point mutations were reported by far. We present a case with growth retardation, small penis, and learning difficulty. Further assessment confirmed growth hormone deficiency, hypogonadotropic hypogonadism (HH), and borderline intellectual disability. He also responded well to gonadotropin-releasing hormone stimulation test, which suggests defects in the hypothalamus, contrary to previous studies that reported defects in the pituitary. A pathogenic frame-shift mutation of SOX3 was found. A heterogeneous missense mutation in SEMA3A was identified in this patient as well, which may also contribute to the development of HH. As far as we know, this is the first report that a frame-shift mutation of SOX3 constitutes rare genetic causes of HH and growth hormone deficiency. Whether mutations in these two genes act synergistically in the pathogenesis of the patient's phenotype remains to be further investigated. We believe that our case extends the phenotypic spectrum and genetic variability of SOX3 mutation. | 10.3389/fendo.2022.810375 |
pubmed_321_20824 | Validation data for segmentation algorithms dedicated to preclinical images is fiercely lacking, especially when compared to the large number of databases of Human brain images and segmentations available to the academic community. Not only is such data essential for validating methods, it is also needed for objectively comparing concurrent algorithms and detect promising paths, as segmentation challenges have shown for clinical images. The dataset we present here is a first step in this direction. It comprises 10 T2-weighted MRIs of healthy adult macaque brains, acquired on a 7 T magnet, along with corresponding manual segmentations into 17 brain anatomic labelled regions spread over 5 hierarchical levels based on a previously published macaque atlas (Calabrese et al., 2015) [1]. By giving access to this unique dataset, we hope to provide a reference needed by the non-human primate imaging community. This dataset was used in an article presenting a new primate brain morphology analysis pipeline, Primatologist (Balbastre et al., 2017) [2]. Data is available through a NITRC repository (https://www.nitrc.org/projects/mircen_macset). | 10.1016/j.dib.2017.11.008 |
pubmed_291_15480 | Psychrotolerant Bacillus-like strains BR035(T) and BR011 were isolated from seawater of the Bering Sea and were characterized by means of a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequences revealed that these strains were related to the members of the genus Bacillus and had the highest 16S rRNA gene sequence similarity with Bacillus korlensis ZLC-26(T). DNA-DNA hybridization experiments confirmed that strains BR035(T) and BR011 belonged to the same species and were distinct from their closest relatives. The cells were Gram-positive, rods, motile, spore-forming and psychrotolerant. The temperature range for growth was 4-42°C. The main respiratory quinone was MK-7. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, an unknown aminolipid and two unknown phospholipids. The major cellular fatty acids were iso-C15:0, anteiso-C15:0, iso-C14:0 and C16:1ω7c alcohol. The diagnostic diamino acid in the cell-wall peptidoglycan was meso-diaminopimelic acid. The genomic DNA G + C content was 37.6-37.8 mol%. On the basis of the phenotypic characteristics, phylogenetic analysis and DNA-DNA relatedness data, a novel species Bacillus beringensis is proposed and the type strain is BR035(T) (=CGMCC 1.9126(T)=DSM 22571(T)). | 10.1007/s10482-010-9523-4 |
pubmed_1015_3105 | Liver scanning with 99mCi 99Tc sulphur-colloid was practiced in 50 patients: 30 suffering from malignant tumors, 10 from hepatic cirrhosis and 10 from pyrexia of unknown origin. Liver radioactivity was recorded by a gamma-camera connected to a computer, 1 frame each 10 seconds for 15 minutes. The spectral analysis of the radioactivity counts taken in different region of interest, showed evidence of a periodic fluctuation, with a period value around 1 minute. Comparative ultrasonographic dynamic study showed evidence of the same phenomena in 16 examined patients. The period of pulsation was found different in each of the following groups: normal liver, cirrhotic, metastatic and infectious diseases. | pubmed_1015_3105 |
pubmed_288_11337 | This study explored possible advantages conferred by the phase shift between leaf phenology and photosynthesis seasonality in a semi-arid Pinus halepensis forest system, not seen in temperate sites. Leaf-scale measurements of gas exchange, nitrogen and phenology were used on daily, seasonal and annual time-scales. Peak photosynthesis was in late winter, when high soil moisture, mild temperatures and low leaf vapour pressure deficit (D(L)) allowed high rates associated with high water- and nitrogen-use efficiencies. Self-sustained new needle growth through the dry and hot summer maximized photosynthesis in the following wet season, without straining carbon storage. Low rates of water loss were associated with increasing sensitivity of stomatal conductance (g(s)) to soil moisture below a relative extractable water (REW) of 0.4, and decreased g(s )sensitivity to D(L) below REW of approx. 0.2. This response was captured by the modified Ball-Berry (Leuning) model. While most physiological parameters and responses measured were typical of temperate pines, the photosynthesis-phenological phasing contributed to high productivity under warm-dry conditions. This contrasts with reported effects of short-term periodical droughts and could lead to different predictions of the effect of warming and drying climate on pine forest productivity. | 10.1111/j.1469-8137.2008.02391.x |
pubmed_626_5382 | High-performance liquid chromatography was used to study the stability of folate vitamers in two types of rye breads after baking and 16 weeks of frozen storage. Bread made using sourdough seeds contained less total folate (74.6 microg/100 g dry basis, expressed as folic acid) than the whole rye flour (79.8 microg/100 g dry basis) and bread leavened only with baker's yeast (82.8 microg/100 g dry basis). Most importantly, it was generated by a significant decrease in 5-CH3-H4folate form. The baking process caused some changes in folate distribution. Storage of breads at -18 degrees C for 2 weeks did not have a significant effect (p < 0.05) on total folates compared to the content directly after baking. After a 5-weeks storage period, a significant decrease (p < 0.05) in the content of total folates was recorded and it dropped on average by 14% for both type of breads. After a longer period of storage (16 weeks), a 25% loss of folates in the bread made with baker's yeast and a 38% loss in the bread fermented with sourdough seeds was found. Retention of 5-CH3-H4folate and 10-HCO-H2folate forms were much lower in the bread made with a sourdough addition than with baker's yeast only. | 10.1007/s11130-009-0114-3 |
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