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pubmed_152_24162
A new epothilone, 10,11-didehydroepothilone D (5), was isolated from a strain of the heterologous host Myxococcus xanthus genetically engineered to produce epothilone D (4). The structure of 5 was determined from NMR and MS data. The epothilone polyketide synthase was further modified in a recombinant M. xanthus strain to produce 5 as the major epothilone-related metabolite. The cytotoxicity of 5 against a panel of tumor cell lines, including several with multidrug resistance, and its effect on tubulin polymerization were comparable to epothilone D (4).
10.1021/np020120f
pubmed_895_311
Developmental studies on wing colour patterns have been performed in nymphalid butterflies, but efficient genetic manipulations, including mutagenesis, have not been well established. Here, we have performed mutagenesis experiments in a lycaenid butterfly, the pale grass blue Zizeeria maha, to produce colour-pattern mutants. We fed the P-generation larvae an artificial diet containing the mutagen ethyl methane sulfonate (EMS), and the F1- and F2-generation adults showed various aberrant colour patterns: dorsoventral transformation, anterioposterior background colouration gap, weak contrast, disarrangement of spots, reduction of the size of spots, loss of spots, fusion of spots, and ectopic spots. Among them, the disarrangement, reduction, and loss of spots were likely produced by the coordinated changes of many spots of a single wing around the discal spot in a system-dependent manner, demonstrating the existence of the central symmetry system. The present study revealed multiple genetic regulations for system-dependent and wing-wide colour-pattern determination in lycaenid butterflies.
10.1038/srep02379
pubmed_86_19606
Longitudinal muscle strips from different sites along the opossum esophagus were stimulated transmurally so as to produce neurally mediated contractions. Low-frequency transmural stimulation produced contractions after termination of the stimulus ("off" contractions), whereas high-frequency stimuli produced contractions beginning during the stimulus and extending beyond termination of the stimulus (extended-duration contractions). The intrastimulus portion of the extended-duration contraction was partially antagonized by atropine or substance P desensitization, whereas the poststimulus portion of the contraction was selectively and fully antagonized by desensitization with substance P. A combination of atropine and substance P desensitization abolished the extended-duration contraction. The amplitude of contraction was greater in the proximal than in the distal strips, irrespective of the mode of stimulation. The poststimulus portion of the extended-duration contraction was significantly longer in muscle strips taken from more distal than proximal portions of the esophagus. This gradient in duration of contractions was abolished by substance P desensitization but was not affected by atropine. Exogenously applied substance P (10 microM) produced equally sustained long-duration contractions at all sites along the esophagus. These observations suggest that a) both acetylcholine- and substance P-containing nerves are responsible for the extended-duration contraction of longitudinal muscle, and b) transmural stimulation causes an aborally directed increase in the duration of contractions; this gradient of increasing duration of contraction appears to be due to a more prolonged neural release of substance P at more distal sites.
10.1152/ajpgi.1986.250.3.G336
pubmed_548_21536
Older people have justifiably been highlighted as a high-risk group with respect to heat wave mortality and morbidity. However, there are older people living within the community who have developed adaptive and resilient environments around their home that provide some protection during periods of extreme heat. This study investigated the housing stock and self-reported thermal comfort of a group of older people living in a regional town in Australia during the summer of 2012. The results indicated that daily maximum living room temperature was not significantly correlated with outdoor temperature, and daily minimum living room temperature was very weakly correlated with outdoor temperature. Residents reported feeling comfortable when indoor temperature approximated 26 °C. As living room temperature increased, indoor thermal comfort decreased. Significant differences between indoor temperatures were noted for homes that were related to house characteristics such as the age of the house, the number of air-conditioning units, the pitch of the roof, home insulation and the number of heat-mitigation modifications made to the home. Brick veneer homes showed smaller diurnal changes in temperature than other building materials. With population ageing and the increasing focus on older people living in the community, the quality of the housing stock available to them will influence their risk of heat exposure during extreme weather.
10.1007/s00484-014-0939-9
pubmed_936_2822
Background It remains controversial whether there is a difference in the prognosis of intracytoplasmic sperm injection (ICSI) using frozen or fresh testicular sperm in patients with obstructive azoospermia (OA). Moreover, in the available studies, few have tracked neonatal outcomes. This study aimed to compare the pregnancy and neonatal outcomes of ICSI using cryopreserved sperm versus fresh sperm collected by testicular sperm aspiration (TESA). Methods A total of 317 OA patients treated with ICSI in a university affiliated hospital from January 2016 to December 2020 were included in this study. The participants were divided into two groups according to the type of sperm used for ICSI: frozen sperm group (n=154) and fresh sperm group (n=163). The pregnancy and neonatal outcomes of the two groups were compared. Results The data produced by this study showed no significant statistical difference in the 2 pronuclei (2PN) fertilization rate, 2PN cleavage rate, high-quality blastocyst rate, and the average number of transferred embryos in the frozen and fresh sperm groups. Similarly, no difference was found in implantation rate, clinical pregnancy rate, multiple pregnancy rate, miscarriage rate, premature delivery rate, live birth rate, and gender ratio at birth (P>0.05). The average newborn birth weight was similar in both groups (2,932.61±728.40 vs. 3,100.32±515.64 g, respectively) (P>0.05). A higher incidence of low birthweight (LBW) newborns was found in the frozen sperm group (20.91% vs. 8.49%) (P<0.05). Multiple logistic regression analysis showed that LBW is related to single or twin pregnancies (P<0.01), but not sperm (frozen or fresh) (P>0.05). We further analyzed the twin and single pregnancies in the two groups separately, and found that the incidences of LBW were both similar (P>0.05). There was no difference in the Apgar scores at 1 min and 5 min after birth between the two groups (P>0.05). Conclusions The use of frozen testicular sperm by TESA was efficient for men with OA. There were similar pregnancy and neonatal outcomes following TESA-ICSI using frozen or fresh sperm in this retrospective study. Prospective investigations are needed for further validation.
10.21037/tau-22-125
pubmed_1089_6329
Studies that have compared different communication systems for individuals with developmental disabilities were systematically reviewed in an effort to provide information useful for clinical decision making and directions for future research. Specifically, 28 studies that compared (a) non-electronic picture systems to speech generating devices, (b) aided AAC (e.g. picture exchange systems and SGDs) to unaided AAC systems (manual sign), or (c) AAC to speech-language interventions were included in this review. Dependent variables forming the basis for comparison included: (a) effectiveness (e.g. acquisition of systems and/or rate of use), (b) efficiency or rate of skill acquisition (c) participants' preference for systems, (d) occurrence of vocalizations and problem behavior, and (e) generalization across communication partners, settings, and time (i.e. maintenance). Results suggest that clear and consistent differences between communication systems are rare, precluding definitive statements regarding a universal best approach for all people with developmental disabilities. Instead, findings of this review support the consideration of an individual's existing skills, goals and preferences as part of the process of selecting an approach to communication.
10.1016/j.ridd.2013.09.017
pubmed_403_8640
BACKGROUND This study aimed to assess how the emergence of high-flow nasal cannula (HFNC) has modified the demographic and clinical characteristics as well as outcomes of infants with bronchiolitis admitted to a pediatric intensive care unit (PICU). METHODS This was a single-center retrospective study including infants aged 1 day to 6 months with bronchiolitis requiring HFNC, noninvasive ventilation (NIV), or invasive ventilation on admission. RESULTS A total of 252 infants (mean age 53±36 days) were included in the study. The use of HFNC increased from 18 (21.4%) during 2013-2014 to 53 infants (55.2%) during 2015-2016. The length of stay in the PICU decreased over time from 4.7±2.9 to 3.5±2.7 days (P<0.01) but the hospital length of stay remained similar (P=0.17). On admission, patients supported by HFNC as the first-line therapy were older. The PICU length of stay was similar according to the type of respiratory support (P=0.16), but the hospital length of stay was longer for patients supported by HFNC (P=0.01). CONCLUSION The distribution of respiratory support has significantly changed over time for patients with bronchiolitis and HFNC is increasingly used. The demographic and clinical characteristics of the have not changed over time. However, the PICU length of stay decreased significantly.
10.1016/j.arcped.2020.11.006
pubmed_313_4603
Anthyllis vulneraria L., Fuchsia sp., Galium mollugo L., and Veronica beccabunga L. were selected to analyse the phenolic content and the antioxidant activity by ferric ion reducing antioxidant power (FRAP) and trolox equivalent antioxidant capacity (TEAC) assays. The highest polyphenol, tannin, and flavonoid contents were measured in Fuchsia species (7.40 ± 0.8, 5.62 ± 0.7 and 0.72 ± 0.1 g/100 g dry weight), while the lowest values were detected in Anthyllis vulneraria (0.68 ± 0.02, 0.17 ± 0.03 and 0.45 ± 0.01 g/100 g dry weight) and Galium mollugo (1.77 ± 0.05, 0.49 ± 0.04 and 0.16 ± 0.06 g/100 g dry weight). The leaf extract of Fuchsia sp. had the highest, while the herb of A. vulneraria had the lowest antioxidant effect measured by both methods, which is probably related to total polyphenol, tannin, and flavonoid contents.
10.1556/018.67.2016.4.10
pubmed_177_9309
Nanotwinned (nt)-metals exhibit superior mechanical and electrical properties compared to their coarse-grained and nanograined counterparts. nt-metals in film and bulk forms are obtained using physical and chemical processes including pulsed electrodeposition (PED), plastic deformation, recrystallization, phase transformation, and sputter deposition. However, currently, there is no process for 3D printing (additive manufacturing) of nt-metals. Microscale 3D printing of nt-Cu is demonstrated with high density of coherent twin boundaries using a new room temperature process based on localized PED (L-PED). The 3D printed nt-Cu is fully dense, with low to none impurities, and low microstructural defects, and without obvious interface between printed layers, which overall result in good mechanical and electrical properties, without any postprocessing steps. The L-PED process enables direct 3D printing of layer-by-layer and complex 3D microscale nt-Cu structures, which may find applications for fabrication of metamaterials, sensors, plasmonics, and micro/nanoelectromechanical systems.
10.1002/adma.201705107
pubmed_538_6348
Cell adhesion molecules, such as integrins, play a vital role in angiogenesis, a key pathway for tumor growth, invasion and metastasis. The integrin alpha(v)beta(3), which recognizes the RGD sequence (Arg-Gly-Asp), may provide a target for in vivo tumor imaging. A linear and a cyclic RGD peptide derivative (RGDfK-His and cRGDfK-His, respectively), labelled via the precursor [99mTc(H2O)3(CO)3]+, were comparatively evaluated and their radiobiological properties were assessed in normal and tumor-bearing mice. Biodistribution studies showed non-specific uptake in all organs, rapid blood clearance and elimination via the hepatobiliary and urinary systems. Tumor uptake was higher for the cyclic radiolabelled derivative, as the both biodistribution and imaging studies suggested. The cRGDfK-His, labelled via the fac-[99mTc(CO)3]-core, may prove to be a useful tool for early tumor detection.
pubmed_538_6348
pubmed_673_2285
Some general aspects of the pathogenesis and the clinical and oral symptoms of chronic lead intoxication are presented. Treatment procedures are briefly discussed. The case of a patient suffering from plumbism is described. A typical Burtonian line was present in the mouth. By electron microprobe analysis, it was shown that this line was mainly the result of lead and, to a minor extent, the result of mercury-, copper-, and iron-bearing pigment in the subepithelial tissue.
10.1016/0030-4220(75)90036-5
pubmed_385_22515
BACKGROUND There is little national research on longitudinal patterns of physical activity and sedentary behavior in ethnically diverse teens as they transition to adulthood. METHODS Longitudinal questionnaire data from U.S. adolescents enrolled in Wave I (1994-1995) and Wave III (2001) of the National Longitudinal Study of Adolescent Health (n =13,030) were analyzed in January 2004. Incidence, reversal, and maintenance of achieving five or more weekly bouts of moderate to vigorous physical activity (MVPA) and < or =14 hours of weekly TV and video viewing, computer/video game use (screen time) were assessed. Multinomial logistic regression models examined the likelihood of achieving five or more weekly sessions of MVPA week and < or =14 hours screen time per week as an adolescent and/or young adult, controlling for household income, parental education, age of adolescent, and seasonality. RESULTS Of those achieving five or more weekly sessions of MVPA and < or =14 hours of weekly screen time as adolescents, few continued to achieve these favorable amounts of activity (4.4%) and screen time (37.0%) as adults. More failed to maintain these favorable amounts of activity (31.1%) and screen time (17.3%) into adulthood. Black versus white females were more likely to maintain less [corrected] favorable amounts of activity from adolescence to adulthood (odds ratio [OR]=3.09; 95% confidence interval [CI]=1.49-6.42), while black males (OR=1.50; CI=1.05-2.14) and females (OR=2.00; CI=1.40-2.87) were more likely than whites to maintain less (versus more) favorable screen time hours. CONCLUSIONS The vast majority of adolescents do not achieve five or more bouts of moderate physical activity per week, and continue to fail to achieve this amount of activity into adulthood.
10.1016/j.amepre.2004.07.006
pubmed_896_14453
Caregiver responses and behaviors often play a significant role in a child's recovery following child sexual abuse (CSA). Caregiver expectations of their child's postabuse functioning has been associated with child symptoms, such that negative expectations lead to worse outcomes for the child. Additionally, caregivers who experienced maltreatment in their own childhood may face difficulties providing support to their child after CSA. Caregivers' own psychological symptoms may influence their expectations for their child's future functioning following CSA. This study utilized structural equation modeling (SEM) to examine the association between caregivers' childhood maltreatment histories, their expectations for their child's future functioning following CSA, and the indirect effect of caregiver depressive symptoms on this relationship. Participants were 354 nonoffending caregivers presenting to treatment with their child following CSA disclosure. Caregivers were 23-72 years old (M = 38.38, SD = 8.02), predominately white, and predominately biological mothers to the youth who were abused. Results indicated that caregivers who experienced maltreatment in childhood were more likely to experience depressive symptoms, which then lead to more negative expectations of their child's future functioning. As negative expectations are associated with poorer outcomes for children following CSA, increased attention to caregivers' depressive symptoms in treatment may promote more positive expectations for their child's postabuse functioning.
10.1177/08862605211043582
pubmed_240_9501
The Arg/Arg genotype versus Arg/Pro or Pro/Pro at codon 72 of the p53 gene in association with human papillomavirus (HPV) 16 E6 variants has been implicated as a risk marker in cervical neoplasia. However, research on this topic has produced controversial results. The association of p53 codon 72 polymorphism alone and in combination with specific HPV 16 E6 variants with risk of developing squamous intraepithelial cervical lesion has been investigated in low and high-grade squamous intraepithelial lesions and in HPV-negative controls from an Italian population. The data obtained showed statistically significant different distribution of p53 genotypes between healthy controls and precursor lesions, with the p53 arginine homozygous increased in high-grade squamous intraepithelial lesions. The T350G HPV 16 variant was the most frequent variant observed in the analyzed group of Italian women, showing a slight decreasing with the severity of the lesion. At the same time, the number of the prototype T350 slightly increased with the severity of the cytological lesions. In conclusion, p53 arginine homozygous was found to be increased in high-grade lesions, supporting the results of previous investigations indicating that HPV-positive patients with p53 Arg/Arg have an increased risk of developing pre-cancerous lesions. In addition, T350G HPV 16 variant was over-represented in p53 Arg homozygous women with cervical lesions. When p53 genotype and HPV 16 variants are considered together, no difference emerges between cases and controls so is not possible to assess that the oncogenic effect of HPV 16 T350G variant may be influenced by the p53 genotype.
10.1002/jmv.23417
pubmed_512_12125
OBJECTIVE To enhance understanding of the possible dangers of large vestibular schwannomas and their potential to cause sudden death through rare situations such as brain herniation precipitated by cerebrospinal fluid pressure shifts. PATIENT An otherwise healthy 32-year-old woman with a magnetic resonance imaging demonstrating a cystic cerebellopontine angle mass, presumptive for vestibular schwannoma, experienced sudden onset of headaches, nausea, and vomiting. INTERVENTION The patient was admitted to the intensive care unit, started on anticonvulsants, investigated with serial computed tomography (CT) scans, and then elective intubation and ventriculostomy when her condition worsened. MAIN OUTCOME MEASURE(S) Clinical and radiological findings, as well as outcome of interventions. RESULTS In the first hours of admission, the patient underwent serial CT scans that demonstrated fourth ventricle compression and hydrocephalus. When the patient's condition worsened, elective intubation was undertaken and an external ventricular drain was inserted. Very high intracranial pressures were noted despite cerebrospinal fluid drainage. Postoperative CT and magnetic resonance imaging demonstrated ascending transtentorial and tonsillar herniation as well as scattered cortical infarcts. Brain death was determined and care was withdrawn 5 days later. CONCLUSION This is a very rare patient report of sudden death caused by a large vestibular schwannoma despite assertive emergent management. There was no intratumoral or intracranial haemorrhage. Brain death was likely a result of ascending transtentorial herniation that can occur with large posterior fossa tumors and be exacerbated by cerebrospinal fluid shifts after ventriculostomy.
10.1097/MAO.0000000000001004
pubmed_1_13472
Spontaneous acute superficial vein thrombosis (SVT) of the leg is now generally recognized as an integral component of venous thromboembolic disease with potentially severe consequences. However, the relatively low grades of some current international recommendations and uncertainty regarding the cost-effectiveness of available therapies may prompt questioning of the real need to treat patients with SVT and explain the persisting heterogeneity of their management in practise. Yet several studies have consistently shown high rates of thromboembolic complications associated with SVT, whether at first presentation or during follow-up. The CALISTO trial established for the first time the clinical benefit of a well-defined anticoagulant regimen for the prevention of serious thromboembolic complications in SVT patients, and we believe that patients such as those included in this trial should receive this regimen as tested. However, several areas of uncertainty remain for categories of SVT patients not evaluated in CALISTO.
10.1111/jth.12925
pubmed_405_19828
The aim of this study is to gain insight into arthritis patients' motives for (not) wanting to be involved in medical decision-making (MDM) and the factors that hinder or promote patient involvement. In-depth semi-structured interviews were conducted with 29 patients suffering from Rheumatoid Arthritis (RA). Many patients perceived the questions about involvement in MDM as difficult, mostly because they were unaware of having a choice. Shared decision-making (SDM) was generally preferred, but the preferred level of involvement varied between and within individuals. Preference regarding involvement may vary according to the type of treatment and the severity of the complaints. A considerable group of respondents would have liked more participation than they had experienced in the past. Perceived barriers could be divided into doctor-related (e.g. a paternalistic attitude), patient-related (e.g. lack of knowledge) and context-related (e.g. too little time to decide) factors. This study demonstrates the complexity of predicting patients' preferences regarding involvement in MDM: most RA patients prefer SDM, but their preference may vary according to the situation they are in and the extent to which they experience barriers in getting more involved. Unawareness of having a choice is still a major barrier for patient participation. The attending physician seems to have an important role as facilitator in enhancing patient participation by raising awareness and offering options, but implementing SDM is a shared responsibility; all parties need to be involved and educated.
10.1007/s10067-014-2820-y
others_331_7463
Australia was once thought to be a biodiversity desert when considering the subterranean world however, recent work has revealed a fascinating collection of cave creatures, many with surprising biogeographic histories. This has especially been so in the karstic regions of north-Western Australia (Cape Range peninsula, Barrow Island, Pilbara), which is home not only to a diverse collection of subterranean invertebrates, but also to the continent's only known underworld-adapted vertebrates, which includes the cave fish in the genus Milyeringa. These cave gudgeons have recently been in a state of taxonomic flux, with species being both split and lumped, but this was done with limited data (incomplete geographic sampling and no nuclear DNA sequence data). Therefore, we have revisited the systematic status of Milyeringa in a total-evidence molecular approach by integrating all existing data (mitochondrial, allozymes) with new DNA sequences from nuclear and mitochondrial loci and new multilocus allozyme data. Our conclusion, that there are two species, matches the most recent taxonomic treatment, with Milyeringa veritas present on both the eastern and western sides of the Cape Range peninsula, and Milyeringa justitia on Barrow Island. This has implications for future research in the linked fields of biogeography and conservation. © 2018 CSIR
10.1071/ZO18008
pubmed_178_11380
The effects of the atomic bomb dropped on Hiroshima and Nagasaki in 1945 are described. Immediately after the bombing, Japanese civilian and military authorities mobilized an intense effort to provide help to the damaged cities and their inhabitants. At the same time, research was undertaken by the Japanese in an attempt to determine the nature of the effects of the bombs on the population. Some weeks later, the American armed services and the Manhattan District also organized an investigation of these effects. This memoir describes the early days of the American research effort, its integration with the Japanese program, and the development of a Joint Commission to study the effects of the bombing. After the first rapid survey, described in this paper, the effort was reorganized and continued under the sponsorship of the National Research Councils of America and Japan as the Atomic Bomb Casualty Commission.
pubmed_178_11380
pubmed_390_7777
A theoretical analysis of cluster formation within the lipid matrix of biological membranes is presented. Various models are analysed: (a) one-dimensional monolayer, (b) two-dimensional monolayer and (c) one dimensional bilayer. Furthermore, lipid-protein interactions are considered. The model is based on differential equations for the probabilities ai and bi which characterize the occupation of the lattice site i by the lipids A and B, respectively. These differential equations are an approximation of the Master-equation. Steady states as well as time-dependent variations are analysed. Depending on the interaction energies of the two lipids, different stationary lipid distributions are obtained, including clusters of lipids A or B and alternating structures. The distributions may be dynamically stable or unstable. It is shown that phase transitions within the lipid matrix may be induced by alteration of the composition of the membrane, by changing the interaction energies of the lipids, by variation of the temperature or by lipid-protein interactions. The transitions between different stationary distributions are studied by use of bifurcation diagrams. The analysis of time-dependent states reveals that unstable structures of the membrane may be important for certain time periods. Consideration of the lipid bilayer leads to a great number of possible distributions, which may be symmetric or asymmetric with respect to the outer and inner leaflets of the membrane.
10.1016/0303-2647(84)90005-4
pubmed_89_3850
Ubiquitin C-terminal hydrolase L1 (UCHL1) is a deubiquitinating enzyme that was originally found in neurons. We found that UCHL1 is highly expressed in slow oxidative skeletal muscles, but its functions remain to be fully understood. In this study, we observed that UCHL1 protein levels in skeletal muscle and C2C12 myotubes were downregulated by fasting or glucose starvation respectively. Skeletal muscle selective knockout (smKO) of UCHL1 resulted in a significant reduction of lipid content in skeletal muscle and improved glucose tolerance. UCHL1 smKO did not significantly change the levels of key proteins involved in oxidative metabolism such as SDHA, Akt, or PDH. Interestingly, while the levels of the major lipases and lipid transporters were unchanged, perilipin 2 was significantly downregulated in UCHL1 smKO muscle. Consistently, in C2C12 myotubes, UCHL1 siRNA knockdown also reduced perilipin 2 protein level. This data suggests that UCHL1 may stabilize perilipin 2 and thus lipid storage in skeletal muscle.
10.3389/fphys.2022.855193
pubmed_957_14369
Panax japonicus, which in the Tujia dialect is known as "Baisan Qi" and "Zhujieshen", is a classic "qi" drug of Tujia ethnomedicine and it has unique effects on disease caused by "qi" stagnation and blood stasis. This paper serves as the basis of further scientific research and development of Panax japonicus. The pharmacology effects of molecular pharmacology were discussed and summarized. P. japonicus plays an important role on several diseases, such as rheumatic arthritis, cancer, cardiovascular agents, and this review provides new insights into P. japonicus as promising agents to substitute ginseng and notoginseng.
10.1016/j.chmed.2020.12.003
pubmed_1072_10609
BACKGROUND This study evaluates a community optometrist-delivered postoperative care scheme in patients discharged from the hospital ophthalmology department following uncomplicated cataract surgery. AIM The aim of this study is to assess the efficacy of electronic patient records (EPR) in facilitating co-managed cataract care. METHODS We performed a retrospective analysis of a prospectively maintained Medisoft EPR database of postoperative cataract review data at a single centre, Sligo University Hospital (SUH), which serves a large and predominantly rural catchment area. All patients undergoing cataract surgery at SUH from October 2012 to September 2013 were included in this study. A total of 39 optometric practices, all with access to the Medisoft EPR software, participated in this pilot co-management scheme. RESULTS One thousand four hundred and twenty-two cataract surgeries were performed in SUH (55% female, 45% male); 1011 patients (71%) were discharged to the community on the day of cataract surgery. Complete postoperative feedback (i.e. data on refraction, visual acuity and intraocular pressure) was available in 97% of these patients compared to 50% of patients reviewed in the hospital. Patients followed up by optometrists were twice as likely to have complete postoperative clinical details (RR = 1.934, 95% CI: 1.759-2.126, p < 0.0001). Overall, 65% of operations were performed on first eyes. Hospital doctors were more likely to document requirement for second eye surgery compared to community optometrists (RR = 1.434, 95% CI: 1.302-1.580, p < 0.0001). CONCLUSIONS Optometrists provided an excellent postoperative care service with superior postoperative feedback rates compared to hospital doctors. EPRs facilitate a postoperative shared-care pathway that is of high quality and efficiency with major economic advantages.
10.1007/s11845-017-1694-9
pubmed_1014_13101
Abnormal excitatory glutamate neurotransmission and plasticity have been implicated in schizophrenia and affective disorders. Gria1-/- mice lacking GluA1 subunit (encoded by Gria1 gene) of AMPA-type glutamate receptor show robust novelty-induced hyperactivity, social deficits and heightened approach features, suggesting that they could be used to test for anti-manic activity of drugs. Here, we tested the efficacy of chronic treatment with established anti-manic drugs on behavioural properties of the Gria1-/- mice. The mice received standard mood stabilizers (lithium and valproate) and novel ones (topiramate and lamotrigine, used more as anticonvulsants) as supplements in rodent chow for at least 4 weeks. All drugs attenuated novelty-induced locomotor hyperactivity of the Gria1-/- mice, especially by promoting the habituation, while none of them attenuated 2-mg/kg amphetamine-induced hyperactivity as compared to control diet. Treatment with lithium and valproate reversed the elevated exploratory activity of Gria1-/- mice. Valproate treatment also reduced struggling behaviour in tail suspension test and restored reciprocally-initiated social contacts of Gria1-/- mice to the level shown by the wild-type Gria1+/+ mice. Gria1-/- mice consumed slightly more sucrose during intermittent sucrose exposure than the wild-types, but ran similar distances on running wheels. These behaviours were not consistently affected by lithium and valproate in the Gria1-/- mice. The efficacy of various anti-manic drug treatments on novelty-induced hyperactivity suggests that the Gria1-/- mouse line can be utilized in screening for new therapeutics.
10.1371/journal.pone.0100188
pubmed_470_10803
A new mixed gas chromatographic stationary phase composed of 2,3,6-tributyl-beta-cyclodextrin and AgNO3(in polyethylene glycol 400) was synthesized for the first time. It was coated on fused silica capillary column. Excellent selectivity was obtained for the separation of seven enantiomeric pairs and four groups of positional isomers of aromatic compounds. The recognition and separation mechanisms were discussed by measuring enthalpy, entropy, free energy and the difference in enthalpy and entropy of these compounds. Results were compared with those obtained on 2,3,6-tributyl-beta-cyclodextrin stationary phase. The results showed that the mixed stationary phase had positive synergistic effects.
pubmed_470_10803
pubmed_509_22986
This paper describes the fabrication of electrically addressable, high-aspect-ratio (>10000:1) nanowires of gold with square cross sections of 100 nm on each side that are separated by gaps of 1.7-2.2 nm which were defined using self-assembled monolayers (SAMs) as templates. We fabricated these nanowires and nanogaps without a clean room or any photo- or electron-beam lithographic processes by mechanically sectioning sandwich structures of gold separated by a SAM using an ultramicrotome. This process is a form of edge lithography known as Nanoskiving. These wires can be manually positioned by transporting them on drops of water and are directly electrically addressable; no further lithography is required to connect them to an electrometer. Once a block has been prepared for Nanoskiving (which takes less than one day), hundreds of thousands of nanogaps can be generated, on demand, at a rate of about one nanogap per second. After ashing the organic components with oxygen plasma, we measured the width of a free-standing gap formed from a SAM of 16-mercaptodohexanoic acid (2.4 nm in length) of 2.6 ± 0.5 nm by transmission electron microscopy. By fitting current-voltage plots of unashed gaps containing three alkanedithiolates of differing lengths to Simmons’ approximation, we derived a value of β = 0.75 Å(-1) (0.94 n(C)(-1)) at 500 mV. This value is in excellent agreement with literature values determined by a variety of methods, demonstrating that the gap-size can be controlled at resolutions as low as 2.5 Å (i.e., two carbon atoms).
10.1021/nn301510x
pubmed_304_18370
The short- and long-term results of surgical treatment were studied in 74 patients with tuberculous spondylitis and in 20 patients with chronic osteomyelitis of the vertebral column. All the patients underwent radical reconstructive operations on the anterior vertebral column if they had an active inflammatory process. The operations were supplemented by an interstitial posterior instrumental fixation with the Hurrington manipulation reduction frames or the plates, developed at the Central Institute of Traumatology and Orthopedics, in 11 cases and with the Cotrel-Dubosse tools in 28 cases. The Cotrel-Dubosse tools were shown to have significant advantages in correcting kyphosis and preventing graft resorption and chronic pain syndrome in tuberculous spondylitis.
pubmed_304_18370
pubmed_591_3859
A widely used method for prediction of complex traits in animal and plant breeding is "genomic best linear unbiased prediction" (GBLUP). In a quantitative genetics setting, BLUP is a linear regression of phenotypes on a pedigree or on a genomic relationship matrix, depending on the type of input information available. Normality of the distributions of random effects and of model residuals is not required for BLUP but a Gaussian assumption is made implicitly. A potential downside is that Gaussian linear regressions are sensitive to outliers, genetic or environmental in origin. We present simple (relative to a fully Bayesian analysis) to implement robust alternatives to BLUP using a linear model with residual t or Laplace distributions instead of a Gaussian one, and evaluate the methods with milk yield records on Italian Brown Swiss cattle, grain yield data in inbred wheat lines, and using three traits measured on accessions of Arabidopsis thaliana. The methods do not use Markov chain Monte Carlo sampling and model hyper-parameters, viewed here as regularization "knobs," are tuned via some cross-validation. Uncertainty of predictions are evaluated by employing bootstrapping or by random reconstruction of training and testing sets. It was found (e.g., test-day milk yield in cows, flowering time and FRIGIDA expression in Arabidopsis) that the best predictions were often those obtained with the robust methods. The results obtained are encouraging and stimulate further investigation and generalization.
10.3389/fgene.2018.00195
pubmed_399_16720
Child sexual abuse prevention programs are a growing phenomenon addressing an expanding number of topics raised by a variety of violent and perverse acts. Currently programs tend to focus on a fairly narrow age group and use an educational model for children. There is a need for broad-based programs with a strong focus on the adults around children. Perinatal prevention programs require an adult focus and must take advantage of a special time in child and family development to address lesson of health and intimacy in a way that may decrease the incidence of future child sexual abuse.
pubmed_399_16720
pubmed_780_12616
Clinical experience indicates that first-time hearing aid users prefer less gain and lower maximum output levels than experienced users. This hypothesis was tested on 20 subjects being fitted with their first aids. The study was double blinded by using a programmable hearing aid, set to either the standard setting according to the manufacturer's software or to reduced gain and maximum output. Half of the subjects started with one hearing aid and half with the other, changing to the other hearing aid after 3 days trial with each setting. At the end of the study, subjects stated preference in specified situations and overall. No significant differences in APHAB, sound quality, estimated communication ability or perceived loudness scores were seen for the two settings. Nine subjects preferred the standard setting, seven the reduced setting and four were undecided. No correlation could be found between preference and audiological variables.
10.1080/010503900750042716
pubmed_880_601
Invasive mould infections (IMI) are associated with significant morbidity and mortality. In vitro studies have demonstrated that hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors (statins) have activity against several pathogenic moulds including Zygomycetes and Aspergillus spp. The aim of our study was to determine if statin use is a preventive factor for the development of IMI. This was a retrospective case-control study of 10 United States Veterans Affairs Medical Centers that comprise the Veterans Integrated Service Network (VISN) 16. Cases with IMI and controls were identified from 2001 to 2008. Controls were matched by age, facility, history of transplantation, presence of chronic steroid use and presence of human immunodeficiency virus infection (HIV). Two hundred and thirty-eight patients were included. Independent variables associated with the development of IMI were history of solid malignant tumours (OR 2.63, 1.41-4.87) and hypertension (OR 2.29, 1.13-4.68). Statin use within 3 months of index date was not an independent variable for prevention or development of IMI. No level of exposure to a statin drug appeared to influence the development of infection. This retrospective case-control study suggests that despite evidence of in vitro activity, statins may not decrease risk of IMI. Prospective, controlled trials may be necessary to investigate any potential clinical benefit.
10.1111/j.1439-0507.2010.01957.x
others_136_8845
In this study, the effects of melatonin or β-glucan treatments on tumor growth, pro-oxidant, and antioxidant status in tumor tissue were investigated in Dunning 3327 MatLyLu prostatic adenocarcinoma model. Prostate cancer (PCa) was induced by single intradermal injection of 2 X 104 MatLyLu cells into the right hind leg of Copenhagen rats. Melatonin (10 mg/kg/daily; IP) or β-glucan (50 mg/kg/daily; orally) treatments applied alone and together continued for 39 days. Melatonin or β-glucan treatments alone or together inhibited tumor growth and decreased malondialdehyde (MDA) levels in tumor tissues of Dunning rats. However, there were no significant differences in tumor volumes and MDA levels among treatment groups. Melatonin and melatonin + β-glucan treatments elevated glutathione (GSH) levels and superoxide dismutase, glutathione peroxidase, and glutathione transferase activities in tumor tissues. However, β-glucan treatment did not influence GSH levels and antioxidant enzyme activities in tumor tissue of Dunning rats. These results indicate that melatonin and β-glucan treatments alone or together inhibit tumor progression and oxidative stress in tumor tissues of rats with Dunning PCa. Copyright © 2011 Cognizant Comm. Corp. All rights reser
10.3727/096504011X13021877989748
pubmed_350_12409
The association of a drug related hypersensitive vasculitis followed two years later by angio-immunoblastic lymphadenopathy is reported. The hypothesis of a similar pathogenesis of these two conditions is discussed.
pubmed_350_12409
pubmed_770_8508
Monoclonal antibodies, specific for either monoamine oxidases A or B, were used to determine the localization of monoamine oxidase in the human brain. Two distinct populations of neurons were detected by immunocytochemical staining. Neurons in regions rich in catecholamines were positive for monoamine oxidase A, including the nucleus locus coeruleus, the nucleus subcoeruleus and the medullary reticular formation. In these regions, monoamine oxidase A could be co-localized with the synthetic enzyme, dopamine-beta-hydroxylase. Neurons in the substantia nigra and the periventricular region of the hypothalamus, areas rich in dopamine neurons, stained for monoamine oxidase A but with much less frequency and intensity. The major accumulation of monoamine oxidase B-positive neurons was observed in the same regions in which monoamine oxidase B is found to co-localize with serotonin in monkey tissues, including the nucleus raphe dorsalis and the nucleus centralis superior. In addition, both monoamine oxidase A and B were localized in distinct populations of neurons in the lateral and tuberal regions of the hypothalamus, a region shown recently to contain histamine neurons in rats. Some glial cells were stained throughout the brain for monoamine oxidase A or B suggesting that glia are capable of either expression or uptake of these proteins.
10.1016/0306-4522(88)90250-3
pubmed_889_23411
INTRODUCTION AND AIM Methotrexate (Mtx) is an antineoplastic and immunosuppressive drug that may cause hepatotoxicity, whereas molsidomine (Mol) is a vasodilating and antioxidant agent. This study aimed to investigate the potential protective effects of Mol in Mtx-induced liver toxicity in rats. MATERIALS AND METHODS Forty Wistar albino rats were equally divided into five groups: control, Mol, Mtx, Mol-Mtx, and Mtx-Mol. Following treatment, the animals were sacrificed, and liver tissue samples were histopathologically evaluated using Roening grading and Bcl-2 antibody staining. Tissue oxidants, antioxidants, and serum transaminases were measured and statistically compared across all groups. RESULTS No hepatic fibrosis or steatosis was observed in any of the groups. In the Mtx group, grade 2 liver injury and score 2 Bcl-2 antibody staining were observed; however, in the Mol-Mtx group, these were lower (grade 1, score 1). There were no statistically significant differences in serum transaminase levels among groups. Malondialdehyde levels were higher in all rats that received Mtx, but no differences in myeloperoxidase levels were observed among the groups. Levels of tissue antioxidants, including superoxide dismutase, glutathione (GSH) peroxidase (GSH-Px), and reduced GSH, were significantly higher in the Mol-treated and Mol pre-treated groups. Catalase (CAT) levels were elevated in all Mol-treated groups, but only in that group were CAT levels statistically significantly higher than in the control group. CONCLUSION Our results suggest that some oxidant levels could increase following Mtx administration in the liver, possibly contributing to liver damage, whereas Mol could mitigate the histopathological and biochemical effects of hepatotoxicity. However, molecular studies are required to understand the exact mechanisms of these alterations.
10.2147/DDDT.S181550
pubmed_763_6756
Leber's hereditary optic neuropathy (LHON) is one of the most common mitochondrial disorders. We report here the clinical, genetic and molecular analysis of mitochondrial DNA (mtDNA) in eight Han Chinese families carrying the known mitochondrial 11778G > A(MT-ND4) mutation. Thirty-seven (26 males/11 females) of 77 matrilineal relatives in these families exhibited the variable severity and age-at-onset of optic neuropathy. The penetrances were from 25% to 75%, with the average of 42%, and the age-at-onset for visual impairment varied from 10 to 25 years, with the average of 17 in these Chinese pedigrees. Molecular analysis of their mtDNA identified distinct sets of variants belonging to the Eastern Asian haplogroupD4j. Except the known m.11778G > A mutation, the m.11696G > A(MT-ND4) mutation caused the substitution of an isoleucine for valineat amino acid position 313, located in a predicted transmembrane region of ND4. And, it is reported that the m.11696G > A mutation was associated with LHON, and appeared to contribute to higher penetrance in these nine Chinese families than other Chinese families carrying only the m.11778G > A mutation. Therefore, the mitochondrial haplogroup D4j specific m.11696G > A mutation may act in synergy with the primary LHON-associated m.11778G > A mutation, thereby increasing the penetrance and expressivity of visual loss in these Chinese families.
10.3109/19401736.2015.1136304
pubmed_241_2544
A survey among pediatric intensive care physicians showed that a great disparity exists between physicians' beliefs regarding hyperglycemia in critically ill patients and their daily practices to screen and treat hyperglycemia. One of the most prominent reasons for hesitating to implement tight glycemic control is the fear of evoking iatrogenic hypoglycemia. Results from ongoing and future studies focusing on both short- and long-term effects of tight glycemic control in broad populations of critically ill children can provide further strong evidence for implementing tight glycemic control. Improving the accuracy of bedside blood glucose measurements and developing reliable computer algorithms to steer insulin infusions can help to overcome the fear of evoking iatrogenic hypoglycemia.
10.1186/cc8984
pubmed_601_4864
Small cell lung cancer (SCLC) displays many unique features which are not present in the other subtypes of lung cancer. The clinical presentation with its unique paraneoplastic syndrome and early metastatic spread make SCLC a protean diagnostic problem. Until recently, SCLC was considered to have the worst prognosis in lung cancer. However the natural history of this cancer has been altered substantially over the past ten years with the application of combined modality therapy using combination chemotherapy and radiation therapy. Numerous clinical trials have demonstrated the four to five fold improvement in survival for patients with limited disease treated with combination chemotherapy and radiation therapy. There are several active chemotherapeutic agents such as cyclophosphamide, doxorubicin, etoposide, vincristine, methotrexate and cisplatinum which are currently used in various combination regimens. The role of radiation therapy is undergoing changes with an improvement in results when used in combination with chemotherapy. It no longer plays a primary role but remains a valuable adjunct in the management of small cell lung cancer. There is a diminishing role for surgery in this type of lung cancer. The therapeutic progress in SCLC has reached a plateau in the past four to five years. However much progress has been made in understanding the biology of SCLC. Armed with a better understanding of the biology of SCLC, we can hopefully formulate better treatment regimens and ultimately further improve therapeutic results.
pubmed_601_4864
pubmed_1081_2904
BACKGROUND Strengthening the health of the young people and adolescents is a priority task for the health care system. The posture, as a habitual position of the body of a person standing at ease, is formed in the course of the child's physical development including the development of the static-dynamic functions. The problems of rehabilitation of the school-age children arising from the necessity to correct impaired posture, including scoliosis, are associated with their life activity and the socio-economic status. The majority of the school-age children spending a lot of time watching TV and playing computer games instead of going in for sports, keep a sedentary lifestyle, do not eat rationally, and experience a deficit of vitamins. These factors contribute to the formation of a weak muscular corset and, as a consequence, lead to the development of an impaired posture. In terms of physical nature, vibration is a mechanical oscillatory motion that repeats itself at certain intervals. The vibrational process of a vibrational impact may exert an appreciable biological effect on the human body; therefore, vibration is extensively used to correct the initial manifestations of the disturbances in the development of posture and strengthen the back muscles. AIM The objective of the present study was to evaluate the influence of the vibrational effect produced by the simulator on the state of the back muscles in the 12-13 years old children presenting with the early signs of scoliosis. METHODS A total of 40 girls at the age of 12-13 years suffering from 1st degree left-sided thoracic spine scoliosis and referred for the rehabilitative treatment were enrolled in the study. The diagnosis of scoliosis was established during a medical examination. The angle of curvature determined as described by V.D. Chaklin was 5-10°. The control group was comprised of 20 schoolgirls engaged in a special rehabilitation program within the framework of the therapeutic physical training (TPT) for 45 minutes three times a week. The main study group consisted of the schoolgirls who performed exercises on the simulator in addition to the special TPT rehabilitation program. When on the vibrating platform in the starting position on all fours, the girls performed the following exercises: (a) exercises with the extension and flexion of the back ('kitty'); (b) the 'boat' exercise made on a special cushion with the retraction of the abdomen, and (c) exercises on a balance with the lifting of the left arm and right leg (or vice versa). The duration of the course was 36 rehabilitation classes. Each lesson lasted 30 minutes. RESULTS The above rehabilitative treatment made it possible to achieve a significant strengthening of the back muscles with increasing their endurance, the improved mobility of the joints of the upper extremities and of the spine joints in the girls of the main group in comparison with those comprising the control group. CONCLUSION The additional and special corrective exercises with the use of the vibration platform performed by the girls with first degree scoliosis greatly contributed to the enhancement of the muscle strength, increased mobility of the spine and the joints of the upper extremities. This allows to conclude that the use of the vibration effect produced by physical exercises on the power plate simulator may provide an efficient tool for the correction of the initial signs of scoliosis and the strengthening of the spine muscles.
10.17116/kurort20189504117
pubmed_372_3690
OBJECTIVES Virtual-assisted lung mapping (VAL-MAP) is a bronchoscopic marking method of dye application on the surface of the lungs before resecting nonpalpable nodules. However, in some cases, it can be difficult to identify the markings of VAL-MAP on computed tomography and intraoperative thoracoscopy. We developed and assessed the feasibility of indocyanine green VAL-MAP (ICG-VAL-MAP). METHODS A historical control trial was conducted to investigate the effectiveness of ICG-VAL-MAP for marking visualization compared with that of VAL-MAP. In ICG-VAL-MAP, instead of indigo carmine, ICG and computed tomography contrast agents were used for dye marking, and near-infrared fluorescence endoscopy was employed to visualize the ICG markings. The other processes in VAL-MAP were carried out. The marking visibility was assessed in 3 grades of easy, faint, or not identifiable. We compared the visibility of the markings on computed tomography images and during thoracoscopic operations between VAL-MAP (567 markings in 147 cases) and ICG-VAL-MAP (142 markings in 63 cases). RESULTS On the preoperative computed tomography images, ICG-VAL-MAP provided significantly better marking visualization than VAL-MAP (easy/faint/not identifiable = 142/0/0 vs 427/100/30; P < .0001). ICG-VAL-MAP provided significantly better intraoperative markings than VAL-MAP (easy/faint/not identifiable = 141/0/1, respectively, vs 475/50/42, respectively; P < .0001). Regarding complications, pneumothorax occurred in 8 (5.4%) cases of VAL-MAP and zero cases (0%) of ICG-VAL-MAP (P = .12); fever was observed in 7 (5.0%) cases of VAL-MAP and 2 (3.2%) cases of ICG-VAL-MAP (P = .72). CONCLUSIONS ICG-VAL-MAP provided significantly better visibility of markings than VAL-MAP. It might be useful in the resection of nonpalpable small lung lesions.
10.1016/j.xjtc.2021.07.019
others_267_13962
A study has been carried out with a breeding purpose on regeneration capability of in vitro cultured embryos with parts of cotyledons, intact cotyledons and endosperm tissue of the new type of the Bulgarian walnut variety Izvor 10 (J. Regia L.) with lateral fruit set, similar to the most famous American cultivars. Explants have been cultured on several different nutrient media at a 16 h photoperiod. Normal plants with well developed central root, stem and leaves have been obtained after 55 days of culturing the embryos with cotyledons on a medium consisting of MS mineral salts and thiamine-HCl 1 mg/l, nicotinic acid 1 mg/l, biotin 0.1 mg/l, pyridoxine-HCl 1 mg/I and calcium panthotenate 1 mg/l, followed by transferring to the same medium with 1'mg/l BAP in addition. Data from the morphological, cytological and histological analyses of regenerates with developmental deviations obtained through direct embryogenesisfrom explants of embryos with cotyledons are presented. © 1993 Taylor & Francis Group, LLC
10.1080/13102818.1993.10818737
pubmed_864_14282
The mitochondrial redox state plays a central role in the link between mitochondrial overloading and insulin resistance. However, the mechanism by which the ROS induce insulin resistance in skeletal muscle cells is not completely understood. We examined the association between mitochondrial function and H2O2 production in insulin resistant cells. Our hypothesis is that the low mitochondrial oxygen consumption leads to elevated ROS production by a mechanism associated with reduced PGC1α transcription and low content of phosphorylated CREB. The cells were transfected with either the encoded sequence for catalase overexpression or the specific siRNA for catalase inhibition. After transfection, myotubes were incubated with palmitic acid (500μM) and the insulin response, as well as mitochondrial function and fatty acid metabolism, was determined. The low mitochondrial oxygen consumption led to elevated ROS production by a mechanism associated with β-oxidation of fatty acids. Rotenone was observed to reduce the ratio of ROS production. The elevated H2O2 production markedly decreased the PGC1α transcription, an effect that was accompanied by a reduced phosphorylation of Akt and CREB. The catalase transfection prevented the reduction in the phosphorylated level of Akt and upregulated the levels of phosphorylated CREB. The mitochondrial function was elevated and H2O2 production reduced, thus increasing the insulin sensitivity. The catalase overexpression improved mitochondrial respiration protecting the cells from fatty acid-induced, insulin resistance. This effect indicates that control of hydrogen peroxide production regulates the mitochondrial respiration preventing the insulin resistance in skeletal muscle cells by a mechanism associated with CREB phosphorylation and β-oxidation of fatty acids.
pubmed_864_14282
pubmed_565_7433
OBJECTIVE Regular consumption of green tea is associated with a reduced risk of mortality due to coronary diseases and cancer. The present study examined whether a green tea extract (GTE) inhibits activation of matrix metalloproteinase-2 (MMP-2), a major collagenase involved in vascular remodeling of atherosclerotic plaques, in vascular smooth muscle cells (VSMCs). METHODS AND RESULTS The expression of MMP-2 was assessed by Northern and Western blot analyses in human aortic VSMCs. MMP-2 activity was evaluated by zymography, membrane-type1-MMP (MT1-MMP, MMP-14) activity by an enzymatic assay, and cell invasion by a modified Boyden chamber assay. The thrombin-induced activation of secreted MMP-2 was abolished by GTE and the green tea polyphenols (-)-epigallocatechin-3-gallate (EGCG) and (-)-epicatechin-3-gallate (ECG). GTE reduced the expression of MMP-2 mRNA and protein. GTE, EGCG and ECG directly inhibited cell-associated MT1-MMP activity, the physiological activator of MMP-2, in a reversible manner. Thrombin-stimulated VSMCs invasion was abolished by EGCG and ECG, and reduced by GTE. CONCLUSIONS GTE inhibits thrombin-induced VSMCs invasion most likely by preventing MMP-2 expression and its activation by a direct inhibition of MT1-MMP. The ability of green tea to prevent cell invasion and matrix degradation might contribute to its protective effect on atherosclerosis and cancer.
10.1016/j.cardiores.2005.03.017
pubmed_1019_1888
The effects of the H(2)O cluster size and the substituent (X=H, Me, OMe, CHO, NO and NO(2)) in the para position of anilide ion on the HN⁻···H-OH→HN-H···OH⁻ switching were investigated by means of B3LYP and MP2 methods. The changes in the H-bond strength due to variation of the substituent and H(2)O cluster size were well monitored by changes in the interaction energy, structural parameter, electron density topology, natural charge, charge transfer and percentage of p-character of N atom in the C-N bond. The HN(-)[Symbol: see text][Symbol: see text][Symbol: see text]H-OH→HN-H[Symbol: see text][Symbol: see text][Symbol: see text]OH(-) switching was enhanced by an increase in the extent of solvation and the insertion of the electron-donating substituents in the para position. The results demonstrate that the strength of the HN(-)∙∙∙HO H-bond increases and that of NH∙∙∙OH(-) H-bond decreases by electron-donating substituents. The reverse situations were found for electron-accepting substituents.
10.1007/s00894-011-1156-7
pubmed_34_16789
The various cellular signalling pathways and biochemical activities involved in apoptotic death are now under intense study in many different laboratories. Recent studies using both molecular cloning approaches and in vitro systems have identified a class of highly specific cellular proteases, termed caspases, that appear to have important roles in apoptotic execution. One of these enzymes may lie near the head of the death pathway in certain cells, whereas others may be involved in the final stages of cellular disassembly. Other recent studies using both live cell and in vitro systems have suggested that mitochondria have an essential role in apoptosis. Mitochondria apparently release at least two factors - a protease and cytochrome C - that are capable of triggering apoptotic changes in isolated cell nuclei. The release of the apoptogenic protease appears to be under the control of the Bcl-2 gene product.
10.1016/S0962-8924(96)10053-2
pubmed_1102_22689
Cerebral malaria (CM) remains a major problem of public health at the world level (Idro et al. 2010; WHO 2009), in spite of numerous efforts from various disciplines to improve our knowledge of disease mechanisms (Hunt and Grau 2003; Schofield and Grau 2005; van der Heyde et al. 2006). Our approach to a better understanding of CM pathogenesis has involved the dissection of immunopathological pathways which, in addition to direct changes caused by malaria parasite-infected erythrocytes (IE), lead to neurovascular lesions. We posited that immunopathology is important in CM because a role for cells and soluble mediators of the immune system has been widely recognised as contributing to the complications of viral, bacterial, fungal and many parasitic infections. As detailed earlier, it would be extraordinary if malaria did not conform to this general pattern. As a matter of fact, there now is strong evidence to support immune mechanisms in malarial pathogenesis (Grau and Hunt 2014).Extracellular vesicles (EV) and their subtypes have been described and reviewed by a number of investigators (Hosseini-Beheshti and Grau 2018, 2019; Raposo and Stahl 2019; Witwer et al. 2017; Zijlstra and Di Vizio 2018) and in others chapters of the present book.
10.1007/978-3-030-67171-6_20
pubmed_994_6279
Magnetic resonance imaging (MRI) captures the dynamics of brain development with multiple modalities that quantify both structure and function. These measurements may yield valuable insights into the neural patterns that mark healthy maturation or that identify early risk for psychiatric disorder. The Pediatric Template of Brain Perfusion (PTBP) is a free and public neuroimaging resource that will help accelerate the understanding of childhood brain development as seen through the lens of multiple modality neuroimaging and in relation to cognitive and environmental factors. The PTBP uses cross-sectional and longitudinal MRI to quantify cortex, white matter, resting state functional connectivity and brain perfusion, as measured by Arterial Spin Labeling (ASL), in 120 children 7-18 years of age. We describe the PTBP and show, as a demonstration of validity, that global summary measurements capture the trajectories that demarcate critical turning points in brain maturation. This novel resource will allow a more detailed understanding of the network-level, structural and functional landmarks that are obtained during normal adolescent brain development.
10.1038/sdata.2015.3
pubmed_154_23519
OBJECTIVE(S) To compare the outcome of patients with stage D1 (TxN+M0) prostate cancer undergoing radical prostatectomy or androgen deprivation alone. PATIENTS AND METHODS Eighty-two patients treated for lymph node positive prostate cancer were retrospectively analyzed for time to progression, tumor-specific and overall survival. Furthermore, subsequent tumor and treatment related morbidity requiring intervention including frequency and duration of associated hospital stays was recorded. RESULTS The extent of lymph node metastasis was significantly lower in 50 patients undergoing radical prostatectomy (+/- early androgen deprivation) compared to 32 receiving androgen deprivation only. The treatment groups, however, did not differ with regard to other characteristics including age, comorbidity, stage, grade and preoperative PSA. Mean actuarial progression-free, and tumor-specific survival was significantly longer for the radical prostatectomy patients (36% and 47%, respectively at 10 years) compared to androgen deprivation (15% and 32%, respectively). The latter group required more secondary interventions resulting in more frequent and overall longer hospital stays. CONCLUSIONS Patients undergoing radical prostatectomy for stage D1 prostate cancer possibly benefit with regard to the necessity for secondary interventions and, at least for limited (solitary) nodal disease, in terms of progression-free and tumor-specific survival. However, the latter observation may be biased by a larger extent of lymph node metastasis in the androgen deprivation group.
10.1016/s0302-2838(02)00134-3
pubmed_204_6414
Here, the authors present the clinical case of a 45-year-old woman with a diagnosis of a chronic periodontal abscess of the tooth #8. After atraumatic dental extraction and bone regeneration with the use of platelet-rich fibrin and bone graft, the area showed excellent bone regeneration with adequate stability of the soft tissue, even 4 months after the surgery.
10.4103/ccd.ccd_283_20
pubmed_1110_17521
We compared rates of unintentional injury (UI) deaths (total and by injury category) among Alaska Native (AN) people to rates of U.S. White (USW) and Alaska White (AKW) populations during 2006-2015. The mortality data for AN and AKW populations were obtained from Alaska Bureau of Vital Statistics and USW mortality data were obtained from WISQARS, the Center for Disease Control and Prevention online injury data program. AN and AKW rates were age-adjusted to the U.S. 2000 Standard Population and rate ratios (RR) were calculated. AN people had higher age-adjusted total UI mortality than the USW (RR = 2.6) and AKW (RR = 2.3) populations. Poisoning was the leading cause of UI death among AN people (35.9 per 100,000), more than twice that of USW (RR = 2.9) and AKW (RR = 2.5). Even greater disparities were found between AN people and USW for: natural environment (RR = 20.7), transport-other land (RR = 12.4), and drowning/submersion (RR = 9.1). Rates of AN UI were markedly higher than rates for either USW or AKW. Identifying all the ways in which alcohol/drugs contribute to UI deaths would aid in prevention efforts. All transportation deaths should be integrated into one fatality rate to provide more consistent comparisons between groups.
10.1080/22423982.2017.1422671
pubmed_525_13554
Finland, located at the edge of the inhabitable world, is one of the best-studied genetic isolates. The characteristic features of population isolates-founder effect, genetic drift and isolation-have, over the centuries, shaped the gene pool of the Finns. Finnish diseases have been a target of extensive genetic research and the majority of some 35 disease genes enriched in this population have been identified; the molecular and cellular consequences of disease mutations are currently being characterized. Special strategies taking advantage of linkage disequilibrium have been efficiently used in the initial mapping and restriction of Finnish disease loci and this has stimulated development of novel statistical approaches in the disease gene hunt. Identification of mutated genes has provided tools for detailed analyses of molecular pathogenesis in Finnish diseases, many of which reveal a distinct tissue specificity of clinical phenotype. Often these studies have not only clarified the molecular detail of Finnish diseases, but also provided novel information on biological processes and metabolic pathways essential for normal development and function of human cells and tissues.
10.1093/hmg/8.10.1913
pubmed_425_1921
PURPOSE The aim of this work was to provide a novel description of how the radiotherapy community configures treatment planning system (TPS) radiation beam models for clinically used treatment machines. Here we describe the results of a survey of self-reported TPS beam modeling parameter values across different C-arm linear accelerators, beam energies, and multileaf collimator (MLC) configurations. ACQUISITION AND VALIDATION METHODS Beam modeling data were acquired via electronic survey implemented through the Imaging and Radiation Oncology Core (IROC) Houston Quality Assurance Center's online facility questionnaire. The survey was open to participation from January 2018 through January 2019 for all institutions monitored by IROC. After quality control, 2818 beam models were collected from 642 institutions. This survey, designed for Eclipse, Pinnacle, and RayStation, instructed physicists to report parameter values used to model the radiation source and MLC for each treatment machine and beam energy used clinically for intensity-modulated radiation therapy. Parameters collected included the effective source/spot size, MLC transmission, dosimetric leaf gap, tongue and groove effect, and other nondosimetric parameters specific to each TPS. To facilitate survey participation, instructions were provided on how to identify requested beam modeling parameters within each TPS environment. DATA FORMAT AND USAGE NOTES Numeric values of the beam modeling parameters are compiled and tabulated according to TPS and calculation algorithm, linear accelerator model class, beam energy, and MLC configuration. Values are also presented as distributions, ranging from the 2.5th to the 97.5th percentile. POTENTIAL APPLICATIONS These data provide an independent guide describing how the radiotherapy community mathematically represents its clinical radiation beams. These distributions may be used by the community for comparison during the commissioning or verification of their TPS beam models. Ultimately, we hope that the current work will allow institutions to spot potentially suspicious parameter values and help ensure more accurate radiotherapy delivery.
10.1002/mp.13892
pubmed_779_24087
BACKGROUND Individuals with lower limb loss are at an increased risk for falls, likely due to impaired balance control. Standing balance is typically explained by double- or single-inverted pendulum models of the hip and/or ankle, neglecting the knee joint. However, recent work suggests knee joint motion contributes toward stabilizing center-of-mass kinematics during standing balance. RESEARCH QUESTION To what extent do hip, knee, and ankle joint motions contribute to postural sway in standing among individuals with lower limb loss? METHODS Forty-two individuals (25 m/17f) with unilateral lower limb loss (30 transtibial, 12 transfemoral) stood quietly with eyes open and eyes closed, for 30 s each, while wearing accelerometers on the pelvis, thigh, shank, and foot. Triaxial inertial measurement units were transformed to inertial anterior-posterior components and sway parameters were computed: ellipse area, root-mean-square, and jerk. A state-space model with a Kalman filter calculated hip, knee, and ankle joint flexion-extension angles and ranges of motion. Multiple linear regression predicted postural sway parameters from intact limb joint ranges of motion, with BMI as a covariate (p < 0.05). RESULTS With eyes open, intact limb hip flexion predicted larger sway ellipse area, whereas hip flexion and knee extension predicted larger sway root-mean-square, and hip flexion, knee extension, and ankle plantarflexion predicted larger sway jerk. With eyes closed, intact limb hip flexion remained the predictor of sway ellipse area; no other joint motions influenced sway parameters in this condition. SIGNIFICANCE Hip, knee, and ankle motions influence postural sway during standing balance among individuals with lower limb loss. Specifically, increasing intact-side hip flexion, knee extension, and ankle plantarflexion motion increased postural sway. With vision removed, a re-weighting of lower limb joint sensory mechanisms may control postural sway, such that increasing sway may be regulated by proximal coordination strategies and vestibular responses, with implications for fall risk.
10.1016/j.gaitpost.2021.06.020
pubmed_900_20465
The importance of correlating anatomical studies with diagnostic and therapeutic approaches in practice has long been recognised. Such studies in the horse have, until recently, lagged behind this discipline in human medicine and surgery. Clinical techniques by which this correlation is achieved include radiography, ultrasound, computed tomography and magnetic resonance imaging. This review presents published literature on the subject and, in addition, describes the part played by plastination, a recently developed technique for the preservation of biological specimens. In this, tissue fluids and part of the lipids are replaced by certain polymers yielding specimens that can be handled without gloves, do not smell or decay, and even retain microscopic properties of the original sample. The technique has proved to be a useful tool to correct previously presented anatomical descriptions and is one now favoured by human surgeons. Studies of the horse employing this technique include those of the temporomandibular joint and tarsus. The aim of the review is to stimulate further correlations of anatomical structure and equine medical and surgical procedures, thereby advancing knowledge and understanding in practice and teaching.
10.2746/042516407x192559
pubmed_958_22801
A 61-year-old woman was admitted for chest discomfort. She had been admitted before, in March 1995, because of a lesion detected on chest roentgenograms. At that time, she was given a diagnosis of mediastinal lipoma based on the findings of chest computed tomography (CT) and magnetic resonance imaging (MRI), but was discharged without active intervention due to lack of subjective symptoms. During follow-up, the patient again reported chest discomfort beginning in March 1998. Because chest radiography disclosed. The tumor had enlarged, the patient was admitted to the hospital by our department. Chest MRI disclosed a mass with a signal intensity equal to that of subcutaneous fat in the pericardial space on both T1-weighted and T2-weighted images. Although sagittal images demonstrated continuity of the mass into intraperitoneal fat, a conclusive diagnosis of diaphragmatic hernia could not be made at that time. On April 30, 1998, a thoracotomy was performed on the basis of a preoperative diagnosis of mediastinal lipoma. During surgery, a hernial ring was observed slightly to the right and behind the sternum. The hernia consisted only of greater omentum, and was diagnosed as Morgagni's foramen hernia.
pubmed_958_22801
pubmed_439_1712
Captive breeding is often a last resort management option in the conservation of endangered species which can in turn lead to increased risk of inbreeding depression and loss of genetic diversity. Thus, recording breeding events via studbook for the purpose of estimating relatedness, and facilitating mating pair selection to minimize inbreeding, is common practice. However, as founder relatedness is often unknown, loss of genetic variation and inbreeding cannot be entirely avoided. Molecular genotyping is slowly being adopted in captive breeding programs, however achieving sufficient resolution can be challenging in small, low diversity, populations. Here, we evaluate the success of the Vancouver Island marmot (Marmota vancouverensis; VIM; among the worlds most endangered mammals) captive breeding program in preventing inbreeding and maintaining genetic diversity. We explored the use of high-throughput amplicon sequencing of microsatellite regions to assay greater genetic variation in both captive and wild populations than traditional length-based fragment analysis. Contrary to other studies, this method did not considerably increase diversity estimates, suggesting: (1) that the technique does not universally improve resolution, and (2) VIM have exceedingly low diversity. Studbook estimates of pairwise relatedness and inbreeding in the current population were weakly, but positively, correlated to molecular estimates. Thus, current studbooks are moderately effective at predicting genetic similarity when founder relatedness is known. Finally, we found that captive and wild populations did not differ in allelic frequencies, and conservation efforts to maintain diversity have been successful with no significant decrease in diversity over the last three generations. Supplementary Information The online version contains supplementary material available at 10.1007/s10592-022-01429-7.
10.1007/s10592-022-01429-7
pubmed_30_10133
The Danop Data System is a microcomputer system designed for the local (ward) surveillance of postoperative surgical infections. The system is served by a simply operated microcomputer program capable of tabulating data input in four standard tables providing continuous information sufficient for surveillance purposes. The aim is that, within a five-year period, 50 per cent of all Danish hospitals will adopt this or similar systems. The system is envisaged as a preliminary to more systematic surveillance of all nosocomial infections.
pubmed_30_10133
pubmed_248_14231
Fertility depends in part on the ability of the spermatozoon to respond to osmotic challenges by regulating its volume, which may rely on the movement of K+. These experiments were designed to characterize the K+ channels possibly involved in volume regulation of human ejaculated spermatozoa by simultaneously exposing them to a physiological hypo-osmotic challenge and a wide range of K+ channel inhibitors. Regulation of cellular volume, as measured by flow cytometry, was inhibited when spermatozoa were exposed to quinine (QUI; 0.3 mM), 4-aminopyridine (4AP; 4 mM) and clofilium (CLO; 10 microM) which suggests the involvement of voltage-gated K+ channels Kv1.4, Kv1.5 and Kv1.7, acid-sensitive channel TASK2 and the beta-subunit minK (IsK) in regulatory volume decrease (RVD). QUI and 4AP and, to some extent, CLO also induced hyper activation-like motility. A sensitivity of RVD to pH could not be demonstrated in spermatozoa to support the involvement of TASK2 channels. Western blotting indicated the presence of Kv1.5, TASK2, TASK3 and minK channel proteins, but not Kv1.4. Furthermore, Kv1.5, minK and TASK2 were localized to various regions of the spermatozoa. Although Kv1.4, Kv1.7, TASK2 and TASK3 channels may have important roles in human spermatozoa, Kv1.5 and minK appear to be the most likely candidates for human sperm RVD, serving as targets for non-hormonal contraception.
10.1093/molehr/gah208
pubmed_583_400
Combinatorial libraries of designed ankyrin repeat proteins (DARPins) have been proven to be a valuable source of specific binding proteins, as they can be expressed at very high levels and are very stable. We report here the selection of DARPins directed against a macromolecular multiprotein complex, the baseplate BppUxBppL complex of the lactococcal phage TP901-1. Using ribosome display, we selected several DARPins that bound specifically to the tip of the receptor-binding protein (RBP, the BppL trimer). The three selected DARPins display high specificity and affinity in the low nanomolar range and bind with a stoichiometry of one DARPin per BppL trimer. The crystal structure of a DARPin complexed with the RBP was solved at 2.1 A resolution. The DARPinxRBP interface is of the concave (DARPin)-convex (RBP) type, typical of other DARPin protein complexes and different from what is observed with a camelid VHH domain, which penetrates the phage p2 RBP inter-monomer interface. Finally, phage infection assays demonstrated that TP901-1 infection of Lactococcus lactis cells was inhibited by each of the three selected DARPins. This study provides proof of concept for the possible use of DARPins to circumvent viral infection. It also provides support for the use of DARPins in co-crystallization, due to their rigidity and their ability to provide multiple crystal contacts.
10.1074/jbc.M109.037812
pubmed_892_10098
BACKGROUND AND PURPOSE Resistance to activated protein C (APC), a natural plasma anticoagulant, is the most common identifiable risk factor for venous thromboembolic disease. One point mutation in coagulation factor V that renders it APC-resistant is found in >90% of APC-resistant venous thrombosis patients. To determine the prevalence of APC resistance and of this factor V mutation in stroke, we screened a group of ischemic stroke patients. METHODS Hispanic ischemic stroke patients were screened using two different activated partial thromboplastin time-based assays. One assay using neat patient plasma determined APC resistance, and the other assay using patient plasma diluted into factor V-deficient plasma determined APC-resistant factor V, including the Arg506-->Gln mutation. Results were compared with those in 31 Hispanic control subjects of similar ages. RESULTS Six of 63 (9.5%) stroke patients had APC resistance compared with none of 31 (0%) control subjects. No patient or control subject had APC-resistant factor V, ie, the factor V Arg506-->Gln mutation. CONCLUSIONS In Hispanic patients with ischemic stroke, the incidence (approximately 10%) of APC resistance is not caused by the factor V Arg506-->Gln mutation. APC resistance not caused by this factor V mutation may be a risk factor for ischemic stroke in this population.
10.1161/01.str.27.7.1163
pubmed_1003_15618
On the basis of the biological activity of neplanocin A and apio-dideoxyadenosine (apio-ddA), novel apio-neplanocin A analogues 5a-d, combining the properties of two nucleosides, were stereoselectively synthesized. The apio moiety of the target nucleosides 5a-d was stereoselectively introduced by treating lactol 10 with 37% formaldehyde in the presence of potassium carbonate. The carbasugar moiety of neplanocin A was successively built by exposing diene 12 on a Grubbs catalyst in methylene chloride. The final nucleosides 5a-d were synthesized from the condensation of the glycosyl donor 14 with nucleic bases under the standard Mitsunobu conditions. Similarly, apio-aristeromycin 6 and (N)-apio-methanocarbaadenosine 7 were derived from the common intermediate 13 using catalytic hydrogenation and Simmons-Smith cyclopropanation as key steps. All of the final nucleosides 5a-d, 6, and 7 did not show significant inhibitory activity against S-adenosylhomocysteine hydrolase (SAH) up to 100 muM, maybe due to the absence of the secondary hydroxyl group at the C3'-position, which should be oxidized by cofactor-bound NAD(+). However, apio-neplanocin A (5a) showed potent and highly selective binding affinity (K(i) = 628 +/- 69 nM) at the A(3) adenosine receptor without any binding affinity at the A(1) and A(2A) adenosine receptors. In conclusion, we have first developed novel carbocyclic nucleosides with unnatural apio-carbasugars using stereoselective hydroxymethylation and RCM reaction and also discovered a new template of human A(3) adenosine receptor agonist, which play a great role in developing new A(3) adenosine receptor agonist as well as in identifying the binding site of the receptor.
10.1021/jo0503207
pubmed_355_2679
Stable isotope 15N-lysine, 15N-alanine and 15N-glycine were used to evaluate the protein metabolism in a patient sustained by TPN for more than 4 years after total small bowel resection. Compared to normal control, the patient's total amount of absorption and urinary excretion were lower but utilization higher, the patient was considered in a status of increased protein synthesis and catabolism. Hence, the patient was vulnerable to nutritional failure if nutrition supply is not efficient. The results suggest that the nutritional program should be individualized, especially in the patient with total small bowel resection.
pubmed_355_2679
others_392_12382
Three North American Pardosa species assigned to the modica group are treated and illustrated. P. tetonensis Gertsch (Wyoming, Montana) is redescribed. P. confusa sp. n. is described on material from Colorado, Utah, and? Oregon. It is morphologically very close to P. tetonen- sis and the two species have not yet been found in sympatry. P. crassistyla sp. n. is described on material from Wyoming, Colorado, Utah, Idaho, Oregon and California; it shows considerable geographic variation in size. © 1987, Brill. All rights reser
10.1163/187631287X00223
pubmed_914_6835
Increased emphasis on reduction of mercury emissions from coal fired electric power plants has resulted in environmental regulations that may in the future require application of activated carbons as mercury sorbents for mercury removal. At the same time, the quantity of poultry manure generated each year is large and technologies that take advantage of the material should be explored. The purpose of the work was to obtain preliminary data to investigate if activated chars made from different poultry manures could adsorb mercury from simulated flue gas. In laboratory experiments, activated chars made from chicken cake and litter removed mercury from the gas as well as a commercial alternative. It was also found that acid-washing these chars after activation may improve pore structure but does not influence the mercury removal efficiency. Activated chars were also made from turkey cake and litter. These raw materials produced activated chars with similar pore structure as those made from chicken manure, but they did not adsorb mercury as well. Acid-washing the turkey manure-based chars improved their performance, but this step would add to the cost of production. Preliminary evaluations suggest that unwashed activated chars may cost as little as $0.95/kg to produce.
10.1016/j.jenvman.2010.06.028
pubmed_112_19770
Incubation of peripheral blood mononuclear cells (PBMNC) from patients with transitional cell carcinoma of the bladder, with interferon (IFN-alpha 2b) causes dose-dependent enhancement of natural killer (NK) and cytotoxic activity. Increased lytic activity was also observed against both NK-sensitive and NK-resistant target cells and T lymphocytes from such patients showed altered activity upon incubation with IFN-alpha 2b. Furthermore, intracavitary instillation of IFN-alpha 2b is associated with infiltration of the bladder wall by NK cells and T lymphocytes. Future work will be aimed at investigating the possible prognostic value of these results as related to the therapeutic effect of intracavitary instillation of IFN-alpha 2b.
10.1097/00001813-199205000-00002
pubmed_515_21794
Membranes play a crucial role in many cellular processes, and it is therefore not surprising that many electron tomographic studies in life sciences concern membranous structures. While these tomographic studies provide many new insights into membrane connections and continuities in three dimensions, they are mostly limited to a macro-morphological level. In this paper, we demonstrate that by combining electron tomography and three-dimensional template matching we are able to investigate membrane morphology at a new level: membrane domains in three dimensions. To test this, temperature induced lipid phase separation in the biological model system of the Escherichia coli bacteria was used. We compared the inner (containing phospholipids) and outer (containing lipopolysaccharides) leaflet of the E. coli outer membrane at both 37 and -20 degrees C, and could visualize how these leaflets react differently to temperature shifts. These findings can be explained by the physico-chemical nature of the building blocks and are in line with earlier published data. This study shows that the combination of electron tomography and template matching is robust enough to visualize membrane domains that are beyond the perception of manual annotation.
10.1016/j.jsb.2009.01.006
pubmed_445_3505
A videodensitometric method for estimating relative flow was employed in a patient with a bovine arteriovenous fistula. Analogous arteriovenous communications of different sizes were created in two dogs for comparison. Local and general hemodynamic parameters were measured. The videodensitometric method proved to be highly accurate compared to electromagnetic flow readings and is the method of choice in estimating shunt flow in connection with routine angiography.
10.1177/028418517902000505
pubmed_859_6307
Acetylcholine (ACh) signaling is critical for central nervous function and is known to be abnormal in schizophrenia (SZ), a chronic neuropsychiatric disorder in which cognitive deficits persist, despite treatment. This review provides a summary of the clinical evidence linking ACh abnormalities to SZ-associated cognitive deficits, an overview of ACh-based pro-cognitive strategies attempted in SZ, and a survey of recent studies that describe the impact of anticholinergic medication burden on cognitive outcomes in SZ. Methodological challenges that currently limit more substantial investigation of ACh in SZ patients and future directions are also discussed.
10.1007/7854_2022_400
pubmed_1053_11951
The CO2 reactivity of blood flow velocity in the Middle Cerebral Artery (MCA) was explored by Doppler ultrasound, in nine patients, at the time of common carotid artery cross-clamping during vascular surgery, in order to detect if a regulatory response apply during operative occlusion of common carotid artery. Transcranial Doppler was used to monitor ipsilateral MCA blood velocity during carotid surgery. MCA velocity, arterial blood pressure and pCO2 (arterial or end-tidal) were measured, during carotid cross clamping, before and after an increase in pCO2 was induced by changing respiratory rate and volumes. No relevant changes in MCA flow velocities were detected in patients with stable arterial blood pressure. In those patients showing an increase in blood pressure during the surgical procedure the MCA velocity increased accordingly. It is suggested that the cross-clamping of common carotid artery is a critical condition in which no regulatory response can be elicited: blood flow velocity tends to parallel the perfusion pressure and also CO2 reactivity is lost.
pubmed_1053_11951
pubmed_182_14365
Invariant floral forms are important for reproductive success and robust to natural perturbations. Petal number, for example, is invariant in Arabidopsis thaliana flowers. However, petal number varies in the closely related species Cardamine hirsuta, and the genetic basis for this difference between species is unknown. Here we show that divergence in the pleiotropic floral regulator APETALA1 (AP1) can account for the species-specific difference in petal number robustness. This large effect of AP1 is explained by epistatic interactions: A. thaliana AP1 confers robustness by masking the phenotypic expression of quantitative trait loci controlling petal number in C. hirsuta. We show that C. hirsuta AP1 fails to complement this function of A. thaliana AP1, conferring variable petal number, and that upstream regulatory regions of AP1 contribute to this divergence. Moreover, variable petal number is maintained in C. hirsuta despite sufficient standing genetic variation in natural accessions to produce plants with four-petalled flowers.
pubmed_182_14365
others_314_70027
Caveolin-1 is the main structural protein of caveolae, small membrane invaginations involved in signal transduction and mechanoprotection. Here, we generated cav1-KO zebrafish lacking Cav1 and caveolae, and investigated the impact of this loss on adult heart function and response to cryoinjury. We found that cardiac function was impaired in adult cav1-KO fish, which showed a significantly decreased ejection fraction and heart rate. Using atomic force microscopy, we detected an increase in the stiffness of epicardial cells and cortical myocardium lacking Cav1/caveolae. This loss of cardiac elasticity might explain the decreased cardiac contraction and function. Surprisingly, cav1-KO mutants were able to regenerate their heart after a cryoinjury but showed a transient decrease in cardiomyocyte prolifera
10.1101/2020.01.16.909267
pubmed_38_5568
There is great diversity in the practice of blood banking and transfusion medicine between countries. We sought to relate this to the variety of health care and blood supply systems in different countries. Questionnaires were completed by respondents from 15 countries selected from among those with higher Human Development Indices. These data were reviewed searching for correlations with blood banking and transfusion medicine practices. Wide varieties of health care and blood supply schemes were documented. There was no apparent relationship between their structure and organization nor their financing arrangements and their proclivity for the implementation of new methods or approaches such as pathogen inactivation and universal leucoreduction. The costs of the operation of the blood supply system as represented by their product fees and the rate of collection of red cells could also not be associated with the factors examined. The diversity of practice evident across developed countries is not explicable solely through their health care and blood supply system structures. Other factors are likely involved but are not easy to define or measure.
10.1111/j.1423-0410.2010.01425.x
pubmed_438_18407
Olfactory neurons are unique in the mammalian nervous system because of their capacity to regenerate in adult animals. It has been shown that olfactory receptor cells located in the olfactory epithelium are replaced on a continuous basis and in response to injury throughout the life span of most species. NGF, which is one of the neurotrophic factors, is present in many areas of the central and peripheral nervous system. It has been shown that NGF in the olfactory bulb plays a role in the survival of cholinergic neurons in the horizontal limb of the diagonal band (HDB). Recent studies of NGF in the olfactory bulb suggest that it is involved in the development, maintenance, and regeneration of olfactory receptor cells. In this study, we review reports examining the relationship between NGF in the olfactory bulb and neuronal regeneration and development in the mammalian olfactory systems. Low- and high-affinity NGF receptor immunoreactivity is markedly expressed during regeneration and at different stages of development in the mouse olfactory system. This level of immunoreactivity is no longer present after completion of regeneration and at maturation. Other findings indicate that NGF injected into the olfactory bulb is transported retrogradely to the olfactory epithelium. It has also been shown that continuous anti-NGF antibody injection into the olfactory bulb causes degeneration and olfactory dysfunction. Administration of NGF directory into nasal cavity results in an increase in the expression of olfactory marker protein within the olfactory epithelium in axotomized rats. These findings suggested that the presence of NGF in the olfactory bulb plays an essential role in regeneration, maintenance, and development in the olfactory system of mammals.
10.1002/jemt.10149
pubmed_732_19217
AIM OF THE STUDY Recent studies showed relatively better outcome for children with refractory (refAML) and relapsed acute myeloid leukemia (relAML). Treatment of these patients has not been unified within Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG) so far. The goal of this study is to analyze the results of this therapy performed between 2005-2011. MATERIAL AND METHODS The outcome data of 16 patients with refAML and 62 with relAML were analyzed retrospectively. Reinduction was usually based on idarubicine, fludarabine and cytarabine with allogenic hematopoietic stem cell transplant (alloHSCT) in 5 refAML and 30 relAML children. RESULTS Seventy seven percent relAML patients entered second complete remission (CR2). Five-year OS and disease-free survival (DFS) were estimated at 16% and 30%. The outcome for patients after alloHSCT in CR2 (63%) was better than that of those not transplanted (36%) with 5-year OS of 34% vs. 2-year of 7% and 5-year DFS of 40% vs. 12.5%. Second complete remission achievement and alloHSCT were the most significant predictors of better prognosis (p = 0.000 and p = 0.024). The outcome of refAML children was significantly worse than relAML with first remission (CR1) rate of 33%, OS and DFS of 25% at 3 years and 53% at 2 years, respectively. All survivors of refAML were treated with alloHSCT after CR1. CONCLUSIONS The uniform reinduction regimen of the documented efficacy and subsequent alloHSCT in remission is needed to improve the outcome for ref/relAML children treated within PPLLSG. The focus should be on the future risk-directed both front and second line AML therapy.
10.5114/wo.2014.40436
pubmed_455_4958
An approach is described to increase the degree of protonation of a polypeptide ion in the gas phase. Sequential charge inversion reactions involving the reactions of oppositely charged ions are used to yield a net increase in ion charge. The approach is illustrated here with the conversion of singly protonated bradykinin to doubly protonated bradykinin. The first step involves conversion of the singly protonated peptide to the singly deprotonated peptide via reactions with multiply charged anions derived from carboxylate-terminated dendrimers. Some of the singly deprotonated peptide was then converted to doubly protonated peptide via reactions with multiply charged cations derived from amino-terminated dendrimers. The overall approach is illustrative of a general strategy for increasing the absolute charge states of large ions in the gas phase.
10.1021/ja0354521
pubmed_1123_14011
Clothianidin was given in the diet to provide levels of 0% (control), 0.003%, 0.006%, and 0.012% from 5 weeks of age of the F(0) generation to 11 weeks of age of the F(1) generation in mice. Selected reproductive and neurobehavioral parameters were measured. In exploratory behavior in the F(0) generation, average time of movement, number of rearing, and rearing time of adult males increased significantly in a dose-related manner. There was no adverse effect of clothianidin on litter size, litter weight, or sex ratio at birth. The average body weight of male and female offspring was increased significantly in a dose-related manner during the early lactation period. With respect to behavioral developmental parameters, swimming head angle at postnatal day (PND) 7 of male offspring was accelerated significantly in a dose-related manner. Negative geotaxis at PND 7 of female offspring was accelerated significantly in a dose-related manner. For movement activity of exploratory behavior in the F(1) generation, number of rearing of female offspring increased significantly in a dose-related manner. Movement time of adult males increased significantly in a dose-related manner. The dose levels of clothianidin in the present study produced several adverse effects in neurobehavioral parameters in mice. Nevertheless, it would appear that the levels of the actual dietary intake of clothianidin are unlikely to produce adverse effects in humans.
10.1002/bdrb.20349
pubmed_665_16699
AIMS To evaluate the efficacy and clinical impact of FDG-PET in patients with suspected recurrent laryngeal carcinoma. MATERIALS AND METHODS 15 patients, with suspicion of recurrent laryngeal carcinoma and ambiguous conventional imaging modalities. In all patients a whole body scan was performed with FDG-PET in fasting patients following i.v. administration of 370-444 MBq FDG. The results were confirmed by histology and clinical evolution (follow-up period > 12 months). RESULTS Prevalence of recurrence was 86.6%. FDG-PET was positive in 13 patients, with confirmation in all cases, and 2 were true negative (TN). Overall sensitivity, specificity, PPV, NPV and accuracy were 100%. FDG-PET changed the modality of treatment in 10 patients (clinical impact 63.3%). CONCLUSIONS FDG-PET has high clinical impact in patients with a suspicion of recurrent laryngeal carcinoma, and should be incorporated to the diagnostic protocols before making a therapy decision.
10.1016/s0001-6519(06)78678-2
others_117_2560
The tobacco BY-2 cell line is one of the most utilized plant cell lines. After long-term culture, the cells turn brown to black, but the causal pigment is unknown. We successfully isolated a blackish-brown pigment from BY-2 cells cultured for 3 weeks. Morphological and spectroscopic analyses indicated that the pigment had similar features to a melanin-like substance reported previously. Furthermore, physicochemical analyses revealed that this pigment possessed most of the properties of melanin-like pigments. In addition, the high nitrogen content suggested that it differed from common plant melanins classified as allomelanins, suggesting a novel eumelanin-like pigment: “BY2-melanin”. This is the first example showing that eumelanin-like pigments are produced in the cultures of plant cells for which the accumulation of melanin has not been reported. This tobacco BY-2 cell culture technique may represent a customizable and sustainable alternative to conventional melanin production platforms, with significant potential for industrial and pharmacological applications. © The Author(s) 2023. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry. All rights reser
10.1093/bbb/zbac214
pubmed_1038_293
Monocytoid B-cell lymphoma (MBCL) is a newly recognized malignant lymphoma that shares clinical and pathologic features with other low-grade B-cell neoplasms, especially small lymphocytic lymphoma and hairy cell leukemia. However, although circulating malignant cells and bone marrow involvement are relatively common in small lymphocytic lymphoma and are characteristic features of hairy cell leukemia, MBCL in the peripheral blood and bone marrow rarely have been described. From 124 patients entered in the MBCL registry, three cases with peripheral blood involvement are described and the clinical and pathologic features in these patients are compared with those of other low-grade B-cell neoplasms. Monocytoid B-cell lymphoma was confirmed by lymph node biopsy in each case. Two patients had lymphocytosis at the time of presentation; the remaining patient presented with pancytopenia. For each patient, phenotypic studies of lymph node and peripheral blood revealed identical monoclonal surface immunoglobulin expression. The morphologic appearance of the circulating MBCL cells was different in each case, varying from a relatively homogeneous population of small lymphocytes to a heterogeneous collection of large and small lymphoid cells. The two patients with lymphocytosis also had extensive replacement of the bone marrow by MBCL; the third patient had diffuse infiltration by MBCL in a normocellular marrow. All three patients had advanced-stage (Stages III or IV) disease, and all required systemic chemotherapy for disease control. The two patients with lymphocytosis had relentless, progressive infirmity despite relatively aggressive treatment regimens. These patients ultimately died of lymphoma 13 and 18 months after initial diagnosis. The third patient is alive and well with stable disease 30 months after coming to the authors' institution. The clinical and pathologic features of the patients reported here reaffirms the placement of MBCL in the spectrum of low-grade B-cell neoplasms. However, unlike small lymphocytic lymphoma and hairy cell leukemia, MBCL only rarely undergoes leukemic conversion. Furthermore, it appears that peripheralization of MBCL occurs primarily in patients with advanced-stage disease and may be indicative of a relentless course and progressive disease despite aggressive chemotherapeutic intervention.
10.1093/ajcp/97.4.591
pubmed_1097_21827
OBJECTIVE Our objective was to provide a scholarly review of the published literature on menopausal hormonal therapy (MHT), make scientifically valid assessments of the available data, and grade the level of evidence available for each clinically important endpoint. PARTICIPANTS IN DEVELOPMENT OF SCIENTIFIC STATEMENT: The 12-member Scientific Statement Task Force of The Endocrine Society selected the leader of the statement development group (R.J.S.) and suggested experts with expertise in specific areas. In conjunction with the Task Force, lead authors (n = 25) and peer reviewers (n = 14) for each specific topic were selected. All discussions regarding content and grading of evidence occurred via teleconference or electronic and written correspondence. No funding was provided to any expert or peer reviewer, and all participants volunteered their time to prepare this Scientific Statement. EVIDENCE Each expert conducted extensive literature searches of case control, cohort, and randomized controlled trials as well as meta-analyses, Cochrane reviews, and Position Statements from other professional societies in order to compile and evaluate available evidence. No unpublished data were used to draw conclusions from the evidence. CONSENSUS PROCESS A consensus was reached after several iterations. Each topic was considered separately, and a consensus was achieved as to content to be included and conclusions reached between the primary author and the peer reviewer specific to that topic. In a separate iteration, the quality of evidence was judged using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system in common use by The Endocrine Society for preparing clinical guidelines. The final iteration involved responses to four levels of additional review: 1) general comments offered by each of the 25 authors; 2) comments of the individual Task Force members; 3) critiques by the reviewers of the Journal of Clinical Endocrinology & Metabolism; and 4) suggestions offered by the Council and members of The Endocrine Society. The lead author compiled each individual topic into a coherent document and finalized the content for the final Statement. The writing process was analogous to preparation of a multiauthored textbook with input from individual authors and the textbook editors. CONCLUSIONS The major conclusions related to the overall benefits and risks of MHT expressed as the number of women per 1000 taking MHT for 5 yr who would experience benefit or harm. Primary areas of benefit included relief of hot flashes and symptoms of urogenital atrophy and prevention of fractures and diabetes. Risks included venothrombotic episodes, stroke, and cholecystitis. In the subgroup of women starting MHT between ages 50 and 59 or less than 10 yr after onset of menopause, congruent trends suggested additional benefit including reduction of overall mortality and coronary artery disease. In this subgroup, estrogen plus some progestogens increased the risk of breast cancer, whereas estrogen alone did not. Beneficial effects on colorectal and endometrial cancer and harmful effects on ovarian cancer occurred but affected only a small number of women. Data from the various Women's Health Initiative studies, which involved women of average age 63, cannot be appropriately applied to calculate risks and benefits of MHT in women starting shortly after menopause. At the present time, assessments of benefit and risk in these younger women are based on lower levels of evidence.
10.1210/jc.2009-2509
pubmed_869_95
Pericardial effusions are a relatively common phenomenon, largely in part due to its many possible etiologies. Although a considerable amount of cases are idiopathic, careful history and physical examination will reveal the etiology in a vast majority of patients. The most effective tools, echocardiography and right heart catheterization, should be aimed not only at the diagnosis of the pericardial effusion, but also to the assessment of the severity of the pericardial effusion, since this will determine that individual patient's management. A small, asymptomatic pleural effusion of known etiology can be treated conservatively, mostly by treating the underlying cause and with careful observation for signs or symptoms of deterioration. Large effusions can be treated with closed pericardiocentesis after routine evaluation for possible etiologies. For patients presenting actual or impending tamponade, the definitive treatment is either closed or open pericardiocentesis, depending on fluid accumulation characteristics, and it should not be delayed for the administration of medical treatment (inotropes, intravenous fluids). Routine evaluation of pericardial fluid is warranted in those cases in which a clear etiology was not established prior to pericardiocentesis.
pubmed_869_95
pubmed_78_11133
Dopamine is found in the nervous systems of both vertebrates and invertebrates. However, the specific actions of dopamine depend on the dopamine receptor type that is expressed in the target cell. As in mammals, different subtypes of dopamine receptors have been cloned and characterized from invertebrates, and these receptor subtypes have different structural and functional properties. Understanding how these receptors respond to dopamine and in which cells each receptor type is expressed is key to our understanding of the role of dopamine signaling. Comparison of the amino acid sequences and experimentally determined functional properties suggest that there are at least three distinct types of dopamine receptors in invertebrates. This review focuses on invertebrate dopamine receptors for which the genes have been isolated and identified, and examines our current knowledge of the functional and structural properties of these receptors, and their pharmacology and expression.
10.1002/arch.20065
pubmed_561_2177
Arrangements that were made to receive and support Kosovan refugees in the United Kingdom should be applied to asylum seekers arriving in the country.
10.1136/jech.56.3.223
others_213_551
ACKGROUND: Achalasia is an esophageal smooth muscle disorder characterized by failure of the lower esophageal sphincter to relax with swallowing. CASE: A 17-year-old primigravid woman with an intrauterine pregnancy at 31+3 weeks reported an unintentional 22.5 kg weight loss in 2 years. Her body mass index was 15.9. Her symptoms included nausea, regurgitation, and worsening dysphagia. MRI suggested achalasia. She was started on total parenteral nutrition until she developed bacteremia. An esophagogastroduodenoscopy with Duotube placement and botulinum toxin A injections were performed. Tube feeds were initiated and continued until the Duotube became obstructed. The patient delivered at 37+4 weeks with mild preeclampsia. A postpartum barium swallow test indicated achalasia. CONCLUSION: A history of dysphagia to solids and/or liquids with weight loss should raise clinical suspicions for achalasia. © Journal of Reproductive Medicine®, I
others_213_551
pubmed_520_1283
BACKGROUND The SARS-COV-2 (Covid-19) pandemic has impacted the management of patients with hematologic disorders. In some entities, an increased risk for Covid-19 infections was reported, whereas others including chronic myeloid leukemia (CML) had a lower mortality. We have analyzed the prevalence of Covid-19 infections in patients with mastocytosis during the Covid-19 pandemic in comparison to data from CML patients and the general Austrian population. MATERIALS AND METHODS The prevalence of infections and PCR-proven Covid-19 infections was analyzed in 92 patients with mastocytosis. As controls, we used 113 patients with CML and the expected prevalence of Covid-19 in the general Austrian population. RESULTS In 25% of the patients with mastocytosis (23/92) signs and symptoms of infection, including fever (n = 11), dry cough (n = 10), sore throat (n = 12), pneumonia (n = 1), and dyspnea (n = 3) were recorded. Two (8.7%) of these symptomatic patients had a PCR-proven Covid-19 infection. Thus, the prevalence of Covid-19 infections in mastocytosis was 2.2%. The number of comorbidities, subtype of mastocytosis, regular exercise, smoking habits, age, or duration of disease at the time of interview did not differ significantly between patients with and without Covid-19 infections. In the CML cohort, 23.9% (27/113) of patients reported signs and symptoms of infection (fever, n = 8; dry cough, n = 17; sore throat, n = 11; dyspnea, n = 5). Six (22.2%) of the symptomatic patients had a PCR-proven Covid-19 infection. The prevalence of Covid-19 in all CML patients was 5.3%. The observed number of Covid-19 infections neither in mastocytosis nor in CML patients differed significantly from the expected number of Covid-19 infections in the Austrian population. CONCLUSIONS Our data show no significant difference in the prevalence of Covid-19 infections among patients with mastocytosis, CML, and the general Austrian population and thus, in mastocytosis, the risk of a Covid-19 infection was not increased compared to the general population.
10.1111/ejh.13875
pubmed_665_16317
Previous studies have shown that sildenafil inhibits the esophageal motility in both humans and animals. The aim of this study was to investigate the effects of sildenafil on intestinal myoelectrical activity and motility. The study was composed of 2 experiments and performed in 7 healthy female dogs with a duodenal cannula 20 cm beyond pylorus (19-26 kg). The first experiment was designed to study the effects of sildenafil on intestinal myoelectrical activity and it included 2 sessions each consisting of 30-minute baseline, 15-minute posttreatment (placebo or 100 mg sildenafil) and 90 minutes after a liquid meal. Intestinal myoelectrical activity was recorded during the entire experiment period. The second experiment was aimed to investigate the effect of sildenafil on intestinal motility and was performed immediately after a solid meal. Intestinal motility was measured by a manometric catheter inserted into the small intestine via the duodenum cannula for 30 minutes at baseline and 60 minutes after sildenafil. Sildenafil significantly reduced the amplitude but had no effect on the frequency and regularity of the intestinal myoelectrical activity. Sildenafil significantly inhibited postprandial intestinal contractions. Although the frequency of the contractions was not altered, the mean area under the curve was significantly reduced during the first 30 minutes (P < .03) and second 30 minutes after sildenafil (P < .03); the power of intestinal contractile activities was also significantly reduced during the first 30 minutes (P < .0004) and second 30 minutes after sildenafil (P < .0003) in comparison with baseline. In conclusion, sildenafil inhibits the amplitude of both intestinal contractile activity and intestinal slow waves.
10.1007/s10620-006-3190-3
pubmed_242_6072
Women and children first! is a phrase rather infamously associated with the sinking Titanic. Although without basis in maritime law, it reflects an ethical imperative to protect those who historically are perceived as the most vulnerable in times of peril, diametrically opposed to the skewed survival-of-the-fittest posture. (Women are of course as fit or fitter than men, but that would take another editorial.) Global commitment to protecting maternal and child health (MCH) is integral to public health, and to sustainable social and economic development as well. The World Bank estimates that the global economic burden of disease could be reduced by up to 30% with optimal implementation of half a dozen cost-effective and affordable public health and clinical services: family planning, antenatal and delivery care, immunization, integrated management of childhood illness and HIV/AIDS prevention. The UN recognized MCH as integral to its Millennium Development Goals. Then last year, the Open Working Group on Sustainable Development Goals post-2015 set specific MCH targets for the world: Goal 3 (Ensure healthy lives and promote wellbeing for all at all ages) includes ending preventable neonatal and under-5 mortality by 2030 and reducing the global maternal mortality ratio to 70 per 100,000 live births (Cuba's was 38.9 in 2013).
10.37757/MR2015.V17.N1.1
pubmed_1109_3231
Coded excitation can improve the SNR in medical ultrasound imaging. In coded excitation, pulse compression is applied to compress the elongated coded signals into a short pulse, which typically requires high computational complexity, i.e., a compression filter with a few hundred coefficients. In this paper, we propose an efficient pulse compression method of chirp-coded excitation, in which the pulse compression is conducted with complex baseband data after downsampling, to lower the computational complexity. In the proposed method, although compression is conducted with the complex data, the L-fold downsampling is applied for reducing both data rates and the number of compression filter coefficients; thus, total computational complexity is reduced to the order of 1/L(2). The proposed method was evaluated with simulation and phantom experiments. From the simulation and experiment results, the proposed pulse compression method produced similar axial resolution compared with the conventional pulse compression method with negligible errors, i.e., ≫36 dB in signal-to-error ratio (SER). These results indicate that the proposed method can maintain the performance of pulse compression of chirp-coded excitation while substantially reducing computational complexity.
10.1109/TUFFC.2013.2815
others_347_4260
Insulinopenic diabetes is known to produce endothelial dysfunction. This dysfunction could arise from either hyperglycemia or inadequate insulin. It is not known whether endothelial dysfunction occurs when hyperglycemia is present with elevated insulin levels. In this study, we utilized an experimental model of hyperglycemia with hyperinsulinemia to investigate latent endothelial dysfunction. Rats were continuously infused with glucose or saline for 72 h to achieve peak plasma glucose concentrations of ~25 mM. Plasma insulin rose by 12-fold in glucose-infused rats. No significant differences in serum electrolyte concentration were noted between control and glucose-infused rats after 72 h. Blood pressure was not altered by this intervention. Aortic rings taken from control rats relaxed to the endothelium-dependent vasodilators, acetylcholine and A-23187, and to the endothelium-independent vasodilator, nitroglycerin. Relaxation to acetylcholine but not to A-23187 or nitroglycerin was impaired in glucose- infused rat aortic rings. Incubation in vitro with either indomethacin or superoxide dismutase did not restore the impaired relaxation to acetylcholine in rings taken from glucose-infused rats. Thus hyperglycemia with hyperinsulinemia selectively impairs receptor-dependent, endothelium- dependent relaxation. These studies suggest that elevated glucose may be a common pathway leading to endothelial dysfunction in insulin-dependent diabetes mellitus and hyperglycemia-induced insulin resistan
10.1152/ajpheart.1995.269.3.h845
pubmed_643_19989
Identifying the unintended effects of drugs (side effects) is a very important issue in pharmacological studies. The laboratory verification of associations between drugs and side effects requires costly, time-intensive research. Thus, an approach to predicting drug side effects based on known side effects, using a computational model, is highly desirable. To provide such a model, we used openly available data resources to model drugs and side effects as a bipartite graph. The drug-drug network is constructed using the word2vec model where the edges between drugs represent the semantic similarity between them. We integrated the bipartite graph and the semantic similarity graph using a matrix factorization method and a diffusion based model. Our results show the effectiveness of this integration by computing weighted (i.e., ranked) predictions of initially unknown links between side effects and drugs.
10.1038/s41598-019-46939-6
pubmed_183_12115
BACKGROUND Respiratory tract infections (RTI) in children is the most common cause of prescription of antibiotics. It is important to describe and analyse non-medical factors in order to develop more rational use of antibiotics. OBJECTIVES To compare families with high and low concern about infectious illness with regard to social variables, perception of infection proneness and beliefs in antibiotics and to relate the concern for infectious illness to reported morbidity, physician consultations and antibiotic prescriptions for the 18-month-old child in the family. METHODS A prospective, population-based survey was performed. During 1 month, all infectious symptoms, physician consultations and antibiotic treatments for 18-month-old children were noted. The 818 families also answered questions about their socio-economic situation, illness perception and concern about infectious illness. RESULTS High concern about infectious illness was associated with more frequent physicians consultations and more prescriptions of antibiotics. There was no significant difference in reported days with symptoms of RTI, but the parents more often experienced their children with RTI without fever as being ill. The variables of infection proneness in the child, inadequate beliefs in antibiotics and the factor of being the only child were important explanatory factors for concern about infectious illness. CONCLUSIONS High concern about infectious illness is an important determining factor for physician consultations and antibiotic prescription for small children. An adequate consultation, where the doctor deals with the parents' worries and gives appropriate information about symptoms and disease, might contribute to less antibiotic prescribing with preserved parental satisfaction.
10.1093/fampra/cmm016
pubmed_93_574
Phytosterol liposomes were prepared using the thin film method and used to encapsulate nattokinase (NK). In order to obtain a high encapsulation efficiency within the liposome, an orthogonal experiment (L9 (3)(4)) was applied to optimise the preparation conditions. The molar ratio of lecithin to phytosterols, NK activity and mass ratio of mannite to lecithin were the main factors that influenced the encapsulation efficiency of the liposomes. Based on the results of a single-factor test, these three factors were chosen for this study. We determined the optimum extraction conditions to be as follows: a molar ratio of lecithin to phytosterol of 2 : 1, NK activity of 2500 U mL⁻¹ and a mass ratio of mannite to lecithin of 3 : 1. Under these optimised conditions, an encapsulation efficiency of 65.25% was achieved, which agreed closely with the predicted result. Moreover, the zeta potential, size distribution and microstructure of the liposomes prepared were measured, and we found that the zeta potential was -51 ± 3 mV and the mean diameter was 194.1 nm. From the results of the scanning electron microscopy, we observed that the phytosterol liposomes were round and regular in shape and showed no aggregation.
10.1080/14786419.2010.528759
pubmed_745_13504
In this study, the effect of polychlorinated biphenyls on retinoid homeostasis was investigated in Sprague-Dawley rats, by analysing [3H]retinoid concentrations in peripheral organs, following exposure to 3,4,3',4'-tetrachlorobiphenyl (TCB). The rats were rendered retinoid-deficient through dietary restriction, followed by dietary supplementation with [3H]retinol for 14 days, in order to facilitate determination of retinoid concentrations in various tissues. At day 7 of [3H]retinol supplementation the rats were exposed to a single i.p. dose of 15 mg TCB dissolved in corn oil/kg body weight. In corn oil-treated control rats, the highest concentrations of [3H]retinoid radioactivity, consisting mainly of retinol and several retinylesters, were obtained in the liver (greater than 10(6) cpm/g,), followed by the kidney and the lung, while only minor concentrations were found in skin and heart. Exposure to TCB resulted in a significant reduction of both retinol and retinylester concentrations in the liver (to 25% of controls) and the lung (to 44% of controls), while in the heart a reduction of retinol to 35% of controls was observed. No significant alterations in retinoid concentrations were observed in the skin and kidney. It is suggested that the reductions in retinoid concentrations might contribute to the toxicological alterations reported in these organs upon exposure to TCB.
10.1016/0300-483x(88)90047-9
pubmed_1110_14797
In Thoroughbred racehorses, fractures of the distal limb are commonly catastrophic. Most of these fractures occur due to the accumulation of fatigue damage from repetitive loading, as evidenced by microdamage at the predilection sites for fracture. Adaptation of the bone in response to training loads is important for fatigue resistance. In order to better understand the mechanism of subchondral bone adaptation to its loading environment, we utilised a square root function defining the relationship between bone volume fraction [Formula: see text] and specific surface [Formula: see text] of the subchondral bone of the lateral condyles of the third metacarpal bone (MCIII) of the racehorse, and using this equation, developed a mathematical model of subchondral bone that adapts to loading conditions observed in vivo. The model is expressed as an ordinary differential equation incorporating a formation rate that is dependent on strain energy density. The loading conditions applied to a selected subchondral region, i.e. volume of interest, were estimated based on joint contact forces sustained by racehorses in training. For each of the initial conditions of [Formula: see text] we found no difference between subsequent homoeostatic [Formula: see text] at any given loading condition, but the time to reach equilibrium differed by initial [Formula: see text] and loading condition. We found that the observed values for [Formula: see text] from the mathematical model output were a good approximation to the existing data for racehorses in training or at rest. This model provides the basis for understanding the effect of changes to training strategies that may reduce the risk of racehorse injury.
10.1007/s10237-017-0998-z
others_318_4901
Rate constants for reactions of a peroxyl (CCl3OO·) and C-centered radicals, that is, phenyl (·C6H4CH2COO-) and vinyl (uracil-5-yl), with an aromatic thiol (p-CH3OC6H4SH) were measured over a pH range (3-12) to include ArSH and ArS- forms. The pH dependence of these rate constants indicates that peroxyl radicals react by a redox mechanism while the C-centered radicals react by an H-atom transfer process. The different mechanisms encountered in the repair of various radicals suggest design features to be incorporated into antiagents, such as radioprotectors and anticarcinogens. © 1987 Pergamon Journals L
10.1016/S0748-5514(86)80074-5
pubmed_726_24094
Microalbuminuria is the strong predictor of diabetic nephropathy, which is the main cause of morbidity and mortality in patients with diabetes mellitus (DM). Microalbuminuria is also characterized by increased prevalence of arterial hypertension, proliferative retinopathy, and peripheral neuropathy. The study was planned to evaluate the effect of Gokshura-Punarnava Basti in the management of microalbuminuria in DM (Madhumeha). Eligible diabetic patients with urine albumin excretion between 30 and 300 mg in 24 h were randomly divided into two groups. Asthapana Basti (decoction enema) of Gokshura and Punarnava Kwatha (decoction), Kalka (paste), Taila (medicated oil), Madhu (honey), and Saindhava (rock salt) for 6 consecutive days and Anuvasana (unctuous enema) of Gokshura-Punarnava Taila on 1(st) and 8(th) day by traditional Basti Putaka method was given in study group. Tablet Enalapril 5 mg, twice daily for 30 days was given to the patients in control group. The primary outcome measures were percentage change in the presenting complaints of diabetes, urine microalbumin, Blood Sugar Level (BSL), and Blood Pressure (BP). Enalapril showed 33.33% improvement, where as Gokshura-Punarnava Basti showed 79.59% improvement in the presenting complaints of diabetes, urine microalbumin, BSL and BP. Gokshura-Punarnava Basti has shown superior results in the management of microalbuminuria in DM as compared to control drug.
10.4103/0974-8520.110535
pubmed_602_22615
OBJECTIVE To study the diurnal rhythm of plasma cortisol and corticosteroid binding-globulin (CBG) in brain-injured patients managed in an intensive care unit (ICU). DESIGN Observational clinical study. SETTING Twelve-bed medical/surgical critical care facility. PATIENTS AND PARTICIPANTS Fifteen acute brain-injured (coma-inducing) patients: nine following trauma and six with subarachnoid haemorrhage (SAH). INTERVENTIONS One morning and one evening blood sample were obtained from each patient via an existing arterial line at times which coincided with clinically indicated blood tests. MEASUREMENTS AND RESULTS The total cortisol measurements in this sample of brain-injured patients is similar to the normal reference range. Only two patients had morning total cortisol measurements greater than the reference range, 140-690 nmol/l, and five patients had evening measurements greater than the 80-330 nmol/l reference range. Eight patients demonstrated diurnal variation of plasma cortisol. Plasma CBG was significantly decreased in all 15 brain-injured patients. All patients had a free cortisol percentage greater than the quoted reference of 5% and five patients had measurements between 12-23%. No diurnal variation in CBG was detected. There was no association between age or mode of injury and cortisol secretion. CONCLUSION Following acute severe brain injury, total serum cortisol is not elevated. This may indicate 'relative' hypocortisolaemia in relation to the clinically assessed stress. However, because of the decline in plasma CBG, plasma free cortisol is increased after acute severe brain injury.
10.1007/s00134-004-2306-5
pubmed_113_6460
The military population face a unique set of risk factors that may increase the risk of being diagnosed with dementia. Traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) have a higher prevalence in this group in comparison to the civilian population. By delving into the individual relationships between TBI and dementia, and PTSD and dementia, we are able to better explore dementia in the military and veteran populations. While there are some inconsistencies in results, the TBI-dementia association has become more widely accepted. Moderate-to-severe TBI has been found to increase the risk of being diagnosed with Alzheimer's disease. A correlation between PTSD and dementia has been established, however, whether or not it is a causal relationship remains unclear. Factors such as blast, combat and chemical exposure may occur during a deployment, along with TBI and/or PTSD diagnosis, and can impact the risk of dementia. However, there is a lack of literature exploring the direct effects of deployment on dementia risk. Sleep problems have been observed to occur in those following TBI, PTSD and deployment. Poor sleep has been associated with possible dementia risk. Although limited studies have focused on the link between sleep and dementia in military and veteran populations, sleep is a valuable factor to study due to its association and interconnection with other military/veteran factors. This review aims to inform of various risk factors to the cognitive health of military members and veterans: TBI, PTSD, deployment, and sleep.
10.1186/s40779-021-00346-z
pubmed_550_21739
The oxidation process is one of the most important natural processes. Oxidative change in diabetes is believed to be an important process in the pathogenesis. Here, the author determines the oxidation flux change in diabetic nephropathy. A simulation test to determine the oxidation flux change based on nano medicine technique is used. An increase in oxidation flux in the diabetic nephropathy can be derived. Therefore, this work can support the finding that the oxidation flux change plays an important role in the pathogenesis of diabetic nephropathy. Conclusively, the oxidative stress can bring glomerulus thickness, and the thickness glomerulus can further amplify the oxidative injuries.
10.1080/08860220701395036
pubmed_595_167
OBJECTIVE To investigate the effects of aminoguanidine on the lung injury induced by the total hepatic ischemia-reperfusion in rats. METHODS The total hepatic ischemia-reperfusion model was built after blocking of the hepatic porta, suprahepatic and infrahepatic vena cava. Ninety Sprague-Dawley rats were assigned randomly into 3 groups: Sham operation group (Group A, n=30); total hepatic ischemia group (Group B, n=30); and aminoguanidine treatment group (Group C, n=30). Each group was subdivided randomly into 3 subgroups (n=10) according to different time phases: 20 minutes after the total hepatic vascular exclusion (T0), 4 hours after the reperfusion (T1), and 48 hours after the survival Group A and Group B were intravenously injected with normal saline ( mL/kg) while Group C was injected with aminoguanidine (20 mg/kg) dissolved in normal saline (1 mL/kg) 10 minutes before the open of the abdomin. The levels of portal blood nitric oxide ( O) endotoxin ( ET), tumor necrosis factor-alpha (TNF-alpha at T0 and T1 were detected; 48 hours survival rates and the lung wet/dry weight ratio were counted; and the histological changes of the lung tissues were observed. RESULTS Compared with Group A, the levels of portal vein NO, ET, and TNF-alpha T0 and T1 in Group B and Group C were significantly higher (P < 0.05 or P < 0.01). But those indexes of Group C were lower than those of Group B (P < 0.05). The 48-hour survival rate in Group C was higher than that in Group B (P < 0.05). The lung wet/dry weight ratio in Group C was lower than in Group B (P < 0.05) and the histological change of Group C was slighter than that in Group B. CONCLUSION Aminoguanidine has the protective effects on the lungs against the total hepatic ischemia-reperfusion induced injury.
pubmed_595_167