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pubmed_319_1803
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Insecticide and repellent activity of an acetone extract and oil from fresh leaves of Pelargonium x hortorum (cv. Orangesonne) were evaluated against the 2nd and 4th instar larvae of Spodoptera littoralis (Boisd.) (Lepidoptera: Noctuidae). The oil showed medium toxicity against the 2nd instar and low toxicity against the 4th instar larvae, while the extract showed high significant toxicity at all concentrations tested against the two instars. On the other hand, both oil and extract exhibited highly significant repellency against the two tested instars. Volatile constituents of the oil were also identified by GC-MS analysis.
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10.1515/znc-2012-7-807
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pubmed_781_15606
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A violent or unstable home life-characterized by caregivers physically or sexually abusing children, physical violence in the home, homelessness, and other factors-and disrupted parental attachment are examined in this secondary data analysis for their possible relationship to juvenile sex offending. Parent or caregiver instability is measured by a demographic questionnaire administered to participants. Parental attachment is measured by the Inventory of Peer and Personal Attachment. The population included 502 adjudicated juvenile male sexual and nonsexual offenders in a Midwest state who responded to questionnaires in order to examine juvenile offending antecedents. The highest correlated parent or caregiver instability variables to juvenile sex offending status were multiple relocations or homelessness, children placed out of the home, slapping or punching in the home, and sexual abuse victimization. The quality of parental attachment had little impact on the respondents' offense status.
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10.1080/10538712.2015.1057668
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pubmed_857_6707
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Recent studies suggest a role for rapid induction of transcription factors in stimulus-induced neuronal plasticity in the mammalian brain. Synaptic activation of transcription factors has been analyzed in the hippocampus using the long-term potentiation or enhancement (LTP/LTE) paradigm. Using this approach, several studies have identified transcription factors that are induced in hippocampal granule cells by NMDA receptor-dependent mechanisms; however, the link between long-term plasticity and activation of these genes has been called into question by reports suggesting that the thresholds for LTE and gene activation differ. To address this issue, we have used a chronic in vivo recording technique to monitor mRNA responses of several transcription factor genes to two different patterns of LTE-inducing electrical stimulation of entorhinal cortical afferents to hippocampus. One pattern consisted of 10 repetitions of a 20 or 25 msec train of pulses at 400 Hz (80 or 100 pulses total). This "10-train" pattern has been used in previous studies of LTE and produces robust synaptic enhancement lasting at least 3 d (Barnes, 1979). The other stimulation pattern consisted of 50 repetitions of a 20 msec train delivered at 400 Hz (400 pulses total), which is similar to parameters used in other studies reporting induction of c-fos in association with LTE (Dragunow et al., 1989; Jeffery et al., 1990; Abraham et al., 1992). Our results indicate that expression of zif268, monitored by in situ hybridization and immunostaining, is strongly induced by the 10-train stimulus pattern to levels similar to those induced by seizure activity. JunB mRNA levels are also modestly increased by the 10-train stimulus pattern; however, increases in JunB immunostaining were not detected. Neither c-fos nor c-jun mRNA were detectably induced by this stimulus. In contrast, the 50-train stimulus pattern resulted in a robust induction of c-fos and c-jun mRNA, in addition to zif268 and junB. Transcription factor responses to either stimulus pattern were blocked by the noncompetitive NMDA receptor antagonist MK-801. Identical transcription factor responses were observed in adult (6-12-month-old) and aged (23-26-month-old) rats, suggesting that synaptic mechanisms involved in these responses are preserved in aged animals. Analysis of LTE following either the 10- or 50-train stimulus patterns revealed identical magnitudes of initial induction and decay kinetics (approximately 3 d) and indicates that the 10-train stimulus pattern is sufficient to produce maximal synaptic enhancement.(ABSTRACT TRUNCATED AT 400 WORDS)
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pubmed_857_6707
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pubmed_498_3586
|
Aortic graft infection is a rare complication after endovascular aneurysm repair that is usually caused by gram-positive organisms such as Staphylococcus spp or gram-negative organisms such as Enterobacteriaceae or Salmonella spp. We have presented a unique case of a patient with acute graft infection secondary to Burkholderia pseudomallei. Because treatment of B. pseudomallei infections is challenging owing to its inherent resistance to multiple antibiotics, we have proposed an approach for managing similar cases in the future. Lifestyle advice on avoiding soil exposure in the postoperative period after endovascular aneurysm repair might be an important preventative measure in endemic regions.
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10.1016/j.jvscit.2021.04.023
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pubmed_916_11867
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Marasmus is a severe form of protein-calorie malnutrition characterized by the depletion of fat stores, muscle wasting, and the lack of edema. In developed countries, marasmus is often the result of anorexia nervosa. Abnormal transaminases with liver synthetic dysfunction have rarely been reported with anorexia nervosa. To our knowledge, we report the first detailed case of acute liver injury with severe coagulopathy (INR > 1.5) in a patient with marasmus due to self-induced calorie restriction caused by a somatic delusional disorder. This case highlights the severity of liver injury that may occur with significant weight loss from self-induced calorie restriction and the rapid normalization of this injury with treatment. It is important for clinicians to be aware of patterns of acute liver injury in patients with severe protein-calorie malnutrition, regardless of the underlying cause.
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10.1155/2011/176894
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pubmed_165_12035
|
This review was designed to provide a detailed analysis of long-term outcome data from treatment studies for panic disorder, with the goal of ascertaining differential efficacy of the available treatments. Studies were included if they were published after 1980 and if follow-up took place at least 6 months after treatment termination. Thirty-one studies were located. A variety of methodological problems were found in these studies, including lack of clarity of diagnosis, lack of clarity in the treatment administered, and inadequately tracked nonstudy treatments during the study and follow-up periods, which limited the information that could be obtained about long-term outcome. Long-term outcome studies that closely track the additional treatments that patients receive are necessary to draw more definitive conclusions about differential treatment efficacy for panic disorder. Available data suggest that there is limited evidence for long-term maintenance of short-term treatment gains in panic disorder patients in the absence of continued treatment.
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10.1097/00005053-199612000-00002
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pubmed_923_1940
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Positron emission tomographic (PET) studies of regional cerebral glucose metabolism were performed in patients with various types of dementia, patients with Parkinson's disease but without dementia, and healthy normal controls. Patients with Alzheimer-type dementia showed significant decreases in glucose metabolism in frontal, temporal, parietal, sensory-motor and striatal regions. Patients with Pick's disease revealed decreased glucose metabolism in frontal and temporal regions. Parkinsonian patients with dementia had significant reductions of glucose metabolism in frontal, temporal, parietal, occipital, sensory-motor and striatal regions. Patients with Huntington's disease revealed decreased glucose metabolism in frontal, parietal and striatal regions. Patients with Creutzfeldt-Jakob's disease showed marked decreases in glucose metabolism throughout all brain regions. On the other hand, patients with Parkinson's disease but without dementia exhibited no reductions of cerebral glucose metabolism. Cerebral glucose hypometabolism in these various types of dementia might reflect neuronal dysfunction and cell death.
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10.1016/0022-510x(93)90040-6
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pubmed_829_20075
|
OBJECTIVE
To determine predictability of at-scene cardiac arrest from a dispatch determined patient history of seizure or epilepsy ("E" history).
DESIGN AND METHODS
A retrospective study of a 1 year dataset from the London Ambulance Service (LAS) National Health Service (NHS) Trust was undertaken. Each of the nine determinant codes on the Medical Priority Dispatch System (MPDS) seizure protocol [Heward A, Damiani M, Hartley-Sharpe C. Does the use of the Advanced Medical Priority Dispatch System affect cardiac arrest detection? Emerg Med J 2004;21:115-8.] was examined for the addition of the "E" suffix finding. The cardiac arrest predictability of cases with reported "E" history was compared to those without using a protocol process to detect the infrequent but predictable presence of seizures caused by anoxic cardiac arrest.
RESULTS
Only protocol codes 12-A-1, 12-D-2, 12-D-3, and 12-D-4 demonstrated significant associations between outcomes and determinant codes (p=0.016, 0.007, <0.001, and 0.048, respectively). These codes showed reduced risk of predicting CA with the "E" suffix protocol determinant codes (RD (95% CI): -0.0025 (-0.0044, -0.0005), chi-square p=0.009; RD (95% CI): -0.0024 (-0.0042, -0.0005), p=0.005; RD (95% CI): -0.020 (-0.029, -0.011), p<0.001; RD (95% CI): -0.01 (-0.017, -0.005), and p=0.034, respectively).
CONCLUSIONS
Knowing whether a seizure patient is an epileptic or has had previous seizures is of clinical value and relevant to dispatch. By improving the discernment of the seizure protocol regarding seizure associated with anoxic cardiac arrest predictability, this information may now be applied at the response level as well as to emergency medical dispatcher's (EMD) decisions to stay on the telephone to enhance the monitoring of these patients.
|
10.1016/j.resuscitation.2007.04.029
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pubmed_978_15617
|
The response to moving light and dark slits was recorded from a total of 94 cells in V1, V2, and V5 (MT) in 9 anesthetized and paralyzed macaque monkeys (M. fascicularis). Using the spatial lag method2, response latencies were calculated for each cell. We obtained median latencies of 85, 96, and 94 ms for cells in areas V1, V2, and V5, respectively. The higher median latencies of V2 and V5 cells compared to V1 are commensurate with later stages of information processing, and are predictable from the anatomy of the interconnections. In addition, a distinct, second population of high-latency cells is present in all 3 regions, but is most abundant in lamina 4 of V5. These may represent either external feedback from other regions or ongoing processing. Extensive overlap of latencies in all 3 regions at both the high and low ends of their respective ranges indicates a considerable degree of parallel interaction between striate and extrastriate cortex.
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10.1016/0006-8993(89)91010-x
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pubmed_16_17983
|
BACKGROUND
Bariatric surgery is a complex procedure not exempt of complications.
AIM
To assess mortality and complications of excisional gastric bypass among morbidly obese subjects.
MATERIAL AND METHODS
Prospective analysis of 684 morbid obese patients (age range 14-70 years, 525 females) subjected to an excisional gastric bypass. Major postoperative complications and mortality were registered.
RESULTS
Mean body mass index (BMI) of the subjects was 43.7 kg/m2. One hundred sixty two patients had a BMI between 35 and 39.9 kg/m2, 419 had a BMI between 40 and 49.9 kg/m2 and 103 had a BMI over 50 kg/m2. Two patients with a BMI of 52 and 56 kg/m2 respectively, died in the postoperative period (0.3%). Thirty six patients had major complications. Anastomotic fistula was the most common complication in 12 patients (1.7%). Fourteen patients required a new operation due to complications. None of these died. The mean operative volume of the surgical team was 124 patients per year.
CONCLUSIONS
Excisional gastric bypass has a low rate of mortality and complications, if the surgical team operates a large volume of patients.
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10.4067/s0034-98872006000700007
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pubmed_975_15563
|
Patients with osteoarthrosis suffer from disability and pain. We measured isokinetic and isometric peak torque in 20 women with gonarthrosis (GA) and in 26 healthy controls. Relationships between muscle strength, walking and stair climbing time, pain level and pain disability scores as assessed by the patients using an extensive questionnaire, radiological changes and subchondral sclerosis expressed as bone mineral density (BMD, g/cm2) of the proximal tibia were studied. Precision errors of the torque measurements in both GA patients and controls were approximately 6%. In the GA patients, isokinetic and isometric quadriceps strength was reduced by 40 and 15% (p < 0.01) respectively, and walking and stair climbing time was increased by 30% (p < 0.005). Isokinetic strength was a better predictor of pain level and pain disability scores than isometric strength and radiological stage. Walking time and stair climbing time were not associated with quadriceps strength, pain level, pain disability scores or radiological changes. Subchondral BMD was not predictive of pain. The study suggests that quadriceps strength assessed by isokinetic dynamometry in GA is a reliable measurement. Isokinetic strength was pronouncedly reduced compared to isometric strength and was a more important predictor of pain and pain disability than isometric strength. These findings should be taken into consideration when planning exercise studies and programmes in GA.
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10.1007/BF02208344
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pubmed_688_3413
|
Endometriosis has been encountered in different sites of the gastrointestinal tract. Involvement of the vermiform appendix, however, is rather unusual. Two cases of appendiceal endometriosis are reported in the present study: one patient had symptoms simulating acute appendicitis; in another patient it was an incidental finding during pelvic surgery. There are no clinical signs and findings pathognomonic of endometriosis of the appendix, but the condition may present as appendicitis. At surgery, the diagnosis can only be suspected when it is associated with obvious genital endometriosis. Correct diagnosis is established by microscopic examination of the lesion. Symptomatic endometriosis of the appendix will be cured by appendectomy.
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pubmed_688_3413
|
pubmed_875_14817
|
Runners increase the risk of becoming hypothermic or hyperthermic by not training in heat before a hot-weather race and by ignoring their body' a warning signs while running. And once thermal injury occurs, diagnosis and treatment may vary according to who is in charge of the medical tent; discrepancies can be fatal.
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10.1080/00913847.1985.11708839
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pubmed_511_23715
|
RIP1 and RIP3 are necroptosis initiators, but their roles in regulation of glycolysis remain elusive. In this study, we found shikonin activated RIP1 and RIP3 in glioma cells in vitro and in vivo, which was accompanied with glycolysis suppression. Further investigation revealed that shikonin-induced decreases of glucose-6-phosphate and pyruvate and downregulation of HK II and PKM2 were significantly prevented when RIP1 or RIP3 was pharmacologically inhibited or genetically knocked down with SiRNA. Moreover, shikonin also triggered accumulation of intracellular H2O2 and depletion of GSH and cysteine. Mitigation of intracellular H2O2 via supplement of GSH reversed shikonin-induced glycolysis suppression. The role of intracellular H2O2 in regulation of glycolysis suppression was further confirmed in the cells treated with exogenous H2O2. Notably, inhibition of RIP1 or RIP3 prevented intracellular H2O2 accumulation, which was correlated with preventing shikonin-induced downregulation of x-CT and depletion of GSH and cysteine. In addition, supplement of pyruvate effectively inhibited shikonin- or exogenous H2O2-induced accumulation of intracellular H2O2 and glioma cell death. Taken together, we demonstrated in this study that RIP1 and RIP3 contributed to shikonin-induced glycolysis suppression via increasing intracellular H2O2.
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10.1016/j.canlet.2018.03.046
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pubmed_46_2820
|
The dynamics of the cationic, bioelectrical and secretory responses to formycin A were monitored in pancreatic islet cells in order to assess whether this adenosine analogue, which is known to be converted to formycin A 5'-triphosphate in isolated islets, triggers the same sequence of ionic events as that otherwise involved in the process of nutrient-stimulated insulin release and currently attributed to an increase in adenosine 5'-triphosphate (ATP) generation rate. Unexpectedly, formycin A first increased 86Rb outflow, decreased 45Ca outflow and inhibited insulin release from prelabelled islets perifused at physiological or higher concentrations of D-glucose. This early inhibitory effect of formycin A upon insulin release coincided, in perforated patch whole-cell recordings, with an initial transient increase of ATP-sensitive K+ channel activity. A positive secretory response to formycin A, still not associated with any decrease in K+ conductance, was only observed either immediately after formycin A administration to islets already exposed to glibenclamide or during prolonged exposure to the adenosine analogue. This coincided with an increase of cytosolic Ca2+ concentration in intact B-cells and a greater increase of membrane capacitance in response to depolarization in B-cells examined in the perforated patch whole-cell configuration. The latter stimulation of exocytotic activity could not be attributed, however, to any increase in peak or integrated Ca2+ current. Thus, the mode of action of formycin A, or its 5'-triphosphate ester, in islet cells obviously differs from that currently ascribed to endogenous ATP in the process of nutrient-stimulated insulin release.
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10.1007/BF02207272
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pubmed_1084_24741
|
Clinical anxiety disorders and elevated levels of anxiety vulnerability are characterized by cognitive biases, and this processing selectivity has been implicated in theoretical accounts of these conditions. We review research that has sought to evaluate the causal contributions such biases make to anxiety dysfunction and to therapeutically alleviate anxiety using cognitive-bias modification (CBM) procedures. After considering the purpose and nature of CBM methodologies, we show that variants designed to modify selective attention (CBM-A) or interpretation (CBM-I) have proven capable of reducing anxiety vulnerability and ameliorating dysfunctional anxiety. In addition to supporting the causal role of cognitive bias in anxiety vulnerability and dysfunction and illuminating the mechanisms that underpin such bias, the findings suggest that CBM procedures may have therapeutic promise within clinical settings. We discuss key issues within this burgeoning field of research and suggest future directions CBM research should take to maximize its theoretical and applied value.
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10.1146/annurev-clinpsy-032511-143052
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pubmed_369_6924
|
The PI3K/Akt signal transduction pathway plays an important role in cancer progression and cell survival. Akt activation is associated with poor outcome in endocrine-treated breast cancer, whereas high levels of cytoplasmic Akt2 are associated with an improved overall survival. Proximity ligation assays (PLAs) were used to determine quantitative expression levels of isoform-specific activation (phosphorylation) of Akt1 and Akt2 in formalin-fixed, paraffin-embedded cell lines and breast cancer tumour tissues in situ. PLAs demonstrated a range of expression in breast cancer samples for total pAkt1 and pAkt2. High levels of pAkt1 were associated with reduced DRFS (HR: 1.45, 95% CI 1.14-1.83, p = 0.002) and OS (HR: 1.42, 95% CI 1.10-1.83, p = 0.007). When PLA results were combined, patients that had high levels of pAkt1 only had a significantly decreased DRFS (HR: 1.92, 95% CI 1.34-2.76, p = 0.005) and OS (HR: 1.94, 95% CI 1.32-2.86, p = 0.008) compared to other patients. Using PLAs to discriminate activation of Akt1 versus Akt2 suggests that Akt1 drives progression in early breast cancers. In cases where both Akt1/Akt2 are activated, Akt2 may act to reverse this effect. Using PLAs, we have measured activation of Akt1 and Akt2 proteins separately in situ in FFPE breast cancer samples.
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10.1002/path.4022
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pubmed_895_13226
|
AIM
To explore the effects of heterodimerization of D2 receptor/A2a receptor (D2R/A2aR) on D2R internalization and D2R downstream signaling in primary cultured striatal neurons and HEK293 cells co-expressing A2aR and D2R in vitro.
METHODS
Primary cultured rat striatal neurons and HEK293 cells co-expressing A2aR and D2R were treated with A2aR- or D2R-specific agonists. D2R internalization was detected using a biotinylation assay and confocal microscopy. ERK, Src kinase and β-arrestin were measured using Western blotting. The interaction between A2aR and D2R was detected using bioluminescence resonance energy transfer (BRET) and immunoprecipitation.
RESULTS
D2R and A2aR were co-localized and formed complexes in striatal neurons, while both the receptors formed heterodimers in the HEK293 cells. In striatal neurons and the HEK293 cells, the D2R agonist quinpirole (1 μmol/L) marked increased Src phosphorylation and β-arrestin recruitment, thereby D2R internalization. Co-treatment with the A2aR antagonist ZM241385 (100 nmol/L) significantly attenuated these D2R-mediated changes. Furthermore, both ZM241385 (100 nmol/L) and the specific Src kinase inhibitor PP2 (5 μmol/L) blocked D2R-mediated ERK phosphorylation. Moreover, expression of the mutant β-arrestin (319-418) significantly attenuated D2R-mediated ERK phosphorylation in HEK293 cells expressing both D2R and A2aR, but not in those expressing D2R alone.
CONCLUSION
A2aR antagonist ZM241385 significantly attenuates D2R internalization and D2R-mediated ERK phosphorylation in striatal neurons, involving Src kinase and β-arrestin. Thus, A2aR/D2R heterodimerization plays important roles in D2R downstream signaling.
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10.1038/aps.2013.87
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pubmed_191_17698
|
BACKGROUND & AIMS
The public health impact of past screening and surveillance practices on the outcomes of Barrett's related cancers has not previously been quantified. Our purpose was to determine the prior prevalence of Barrett's esophagus in reported cases of incident adenocarcinoma undergoing resection, as an indirect measure of impact.
METHODS
We performed a systematic review of the literature from 1966 to 2000. Studies were included if they reported: (1) the number of consecutive adenocarcinomas resected, and (2) the number of those resected who had a previously known diagnosis of Barrett's. We generated summary estimates using a random effects model.
RESULTS
We identified and reviewed 752 studies. Twelve studies representing a total of 1503 unique cases of resected adenocarcinomas met inclusion criteria. Using a random effects model, the overall percentage of patients undergoing resection who had a prior diagnosis of Barrett's was 4.7% +/- 2.9%.
CONCLUSIONS
The low prior prevalence (approximately 5%) of Barrett's esophagus in this study population provides indirect evidence to suggest that recent efforts to identify patients with Barrett's-whether through endoscopic screening or evaluation of symptomatic patients-have had minimal public health impact on esophageal adenocarcinoma outcomes. The potential benefits of endoscopic surveillance seem to have been limited to only a fraction of those individuals at risk. These data thus provide a clear and compelling rationale for the development of effective screening strategies to identify patients with Barrett's esophagus.
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10.1053/gast.2002.30297
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pubmed_642_12452
|
The term dance encompasses a broad range of different styles; much of the orthopaedic literature has focused on ballet dancers. Injury is common in dancers at all levels, and many serious dancers sustain multiple injuries as they progress through their career. Foot and ankle injuries are among the most common injuries experienced by dancers. These injuries include those that are specific to dancers because of the unique physical maneuvers required to effectively perform, but they can also include common injuries that may require relatively different treatment because of the physical demands of the dancer. Os trigonum syndrome and flexor hallucis longus tenosynovitis generally fall into the former category as they are injuries that are more prevalent in dancers due to the extreme plantarflexion involved in dancing, especially ballet, and the relative demand placed on the toe flexors, most notably the flexor hallucis longus. On the other hand, anterior ankle impingement occurs both in dancers and in the general public. In many cases, a team approach to treatment with knowledgeable physical therapists can obviate the need for surgical treatment. If surgical treatment proves necessary, good results can be achieved with sound surgical technique and a well thought-out rehabilitation program.
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10.5435/JAAOS-D-18-00596
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pubmed_382_6842
|
The haemagglutination and tissue culture adherence properties of 20 isolates of Moraxella catarrhalis obtained from the sputum of elderly patients with lower respiratory tract infections were compared with those of 20 isolates of M. catarrhalis obtained from the nasopharynx of elderly persons colonised by the organism. Eighty percent of isolates from the infected group as opposed to 5% of isolates from the colonised group haemagglutinated human erythrocytes (P < 0.001), indicating that the haemagglutinin might be a marker of pathogenicity for M. catarrhalis. There was a significant difference in the adherence to HEp-2 cells of isolates from the infected group in comparison to isolates from the colonised group (P = 0.03). Haemagglutination and tissue culture adherence properties were unrelated, indicating that separate adhesin systems are involved. The adherence of M. catarrhalis to HEp-2 cells was unaffected following pronase and trypsin treatment, however, sodium periodate pre-treatment of the bacteria significantly reduced the tissue culture adherence index, indicating that the adhesin by which the bacteria bind to HEp-2 cells may have a carbohydrate moiety. Transmission electron microscopy studies revealed that adherence of M. catarrhalis to HEp-2 cells was mediated by trypsin-resistant 'tack-/spicule-like' structures protruding from the surface of the bacteria.
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10.1111/j.1574-695X.1999.tb01271.x
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pubmed_322_16282
|
The coronavirus disease 2019 (COVID-2019) and the consequences of the pandemic on individuals' social, economic, and public lives are assumed to have major implications for the mental health of the general population but also for patients already diagnosed with psychological disorders. The aim of the present study was to investigate the psychological distress during the COVID-19 pandemic in patients with psychological disorders or physical health conditions in inpatient mental and physical treatment programs. A total 2710 patients completed COVID-19 related questions concerning their psychological distress and financial burden during the pandemic. Patients with psychological disorders reported the highest level of psychological distress and financial burden compared to patients with physical health conditions. Furthermore, most patients with psychological disorders attributed their individual psychological distress to the COVID-19 pandemic. In comparison to patients with physical health conditions, patients with psychological disorders are more strongly impacted by the COVID-19 pandemic and have an additional need for psychological/psychotherapeutic treatment due to the COVID-19 crisis. The findings stress the importance of continuous psychosocial support and availability of psychosocial support services for patients with psychological disorders during the pandemic.
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10.3389/fpsyg.2021.703488
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pubmed_43_12588
|
Adenomatoid odontogenic tumor (AOT) with its unique and varied presentations histologically and clinically has always been an enigma. AOTs are multifaceted in their appearance with reports pointing out to its occurrence as a synchronous tumor, a purely cystic variant or with multiple foci; however, the three commonly encountered forms are Follicular/Coronal, Extra Follicular/Extra Coronal and Peripheral variants. Here, we present a subtype of the Peripheral AOT (PAOT) seen synchronous with an intraosseous cystic variant of AOT in a 16-year-old female in the anterior mandible. This case is unique in that a PAOT occurring adjacent to a focally aggressive intraosseous cystic AOT (not associated with impacted tooth) could either be synchronous with no connection to the intraosseous component or could actually be an erupted intraosseous cystic variant with peripheral manifestation. Features of cortical expansion, perforation and displacement of teeth without resorption were seen. Histologically, all the classical features of AOT along with abundant eosinophilic amorphous fibrinous deposits, cellular vacuolization, clearing of cells, dystrophic and reactive bone formation and a cystic lining were seen. Thus, this case of PAOT would add to the myriad presentation of AOT making it one of the most often discussed odontogenic tumor.
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10.4103/jomfp.jomfp_450_20
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pubmed_248_2713
|
In situ estrogen metabolism and synthesis have been considered to play a very important role in the development and progression of human endometrial carcinoma. 17Beta-hydroxysteroid dehydrogenases (17-HSDs) are enzymes involved in the formation of active sex steroids, including testosterone, estrone (E1) and estradiol (E2). Estrogens are interchanged by two enzymes, 17-HSD types 1 and 2, type 1 converts E1 to E2, and type 2 does reverse actions. 17-HSD type 5 catalyzes the reduction of androstenedione to testosterone. 17-HSD type 2 expression was decreased through normal endometrium, hyperplasia and carcinoma accordingly. There was a significant inverse correlation between intratumoral E2 concentration and the level of 17-HSD type 2 mRNA in endometrial carcinoma. 17-HSD type 5 expression was significantly increased through normal endometrium, hyperplasia and carcinoma accordingly. These results indicated that 17-HSD types 2 and 5 play an important role in the regulation of in situ estrogen production in endometrial carcinoma.
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10.1016/j.mce.2005.11.038
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pubmed_508_24925
|
BACKGROUND
Celiac Disease (CD) is present in 1-16.4% of patients with type 1 diabetes mellitus. The most important serological markers of CD are anti-endomysial (EMA), anti-tissue transglutaminase (tTGA) and antigliadin antibodies (AGA).
AIM/HYPOTHESIS
The objective of this work is to determine the frequency of tTGA and/or AGA in latent autoimmune diabetes of adult (LADA) and subjects with type 2 diabetes (T2DM), as well as to evaluate their relation with several clinical and biochemical characteristics.
SUBJECTS AND METHODS
Forty three subjects with LADA and 99 with T2DM were studied. The presence of AGA, tTGA was determined in the sera of these patients. The variables: sex, age, duration of diabetes, treatment, body mass index (BMI) and fasting blood glucose concentration were also recorded.
RESULTS
No differences were found in the frequency of celiac disease associated antibodies between LADA and T2DM subjects. The presence of celiac disease related antibodies was more frequent in patients with a normal or low BMI.
CONCLUSIONS
Celiac disease does not seem to be related with pancreatic autoimmunity in type 2 diabetes. Celiac disease causes a decrease of body mass index in type 2 diabetes while pancreatic islet autoimmunity in this entity masks this effect.
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10.1080/08916930601118825
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pubmed_1111_2845
|
BACKGROUND
Convection-enhanced delivery (CED) permits site-specific therapeutic drug delivery within interstitial spaces at increased dosages through circumvention of the blood-brain barrier. CED is currently limited by suboptimal methodologies for monitoring the delivery of therapeutic agents that would permit technical optimization and enhanced therapeutic efficacy.
OBJECTIVE
To determine whether a readily available small-molecule MRI contrast agent, gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA), could effectively track the distribution of larger therapeutic agents.
METHODS
Gd-DTPA was coinfused with the larger molecular tracer, I-labeled human serum albumin (I-HSA), during CED of an EGFRvIII-specific immunotoxin as part of treatment for a patient with glioblastoma.
RESULTS
Infusion of both tracers was safe in this patient. Analysis of both Gd-DTPA and I-HSA during and after infusion revealed a high degree of anatomical and volumetric overlap.
CONCLUSION
Gd-DTPA may be able to accurately demonstrate the anatomic and volumetric distribution of large molecules used for antitumor therapy with high resolution and in combination with fluid-attenuated inversion recovery (FLAIR) imaging, and provide additional information about leaks into cerebrospinal fluid spaces and resection cavities. Similar studies should be performed in additional patients to validate our findings and help refine the methodologies we used.
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10.1227/NEU.0b013e3182181ba8
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pubmed_656_11841
|
Objective: The survival of prostate cancer (PC) patients after radiotherapy (RT) has improved over time, but it raises the debate of increased risk of secondary colorectal cancer (SCRC). This study aimed to assess whether RT for PC treatment increases the risk of SCRC in comparison with radical prostatectomy (RP). Methods: A population-based cohort of PC patients treated only with RT or only with RP between January 2007 and December 2015 was identified from the Taiwan Cancer Registry. The incidence rate of SCRC development was estimated using Cox regression model. Results: In this study, total 8,797 PC patients treated with either RT (n = 3,219) or RP (n =5,578). Patients subjected to RT were elder (higher percentage of 70≧years, p < 0.0001) and more advanced clinically (stage III: 22.90% vs. 11.87%; stage IV: 22.15% vs. 13.80%, p < 0.0001), compared to those subjected to RP. More patients subjected to RT had a much higher percentage of autoimmune disease (22.34% vs. 18.75%, p < 0.0001) and osteoarthritis and allied disorders (16.31% vs. 12.98%, p < 0.0001). Besides, RT patients had a higher percentage of underlying Crohn's disease (0.25% vs. 0.05%, p = 0.0230). Although almost all selected factors were not statistically significant, they presented the positive risk of SCRC for those under RP compared with those among RT. Besides, for PC patients in clinical stage I and II, patients with RP may have borderline significantly protective effects of SCRC compared with those under RT (stage I, HR: 0.14; 95% C.I.:0.01-1.39; p = 0.0929; stage II, HR: 1.92; 95% C.I.:0.93-3.95; p = 0.0775). Kaplan-Meier curves for a 3-year-period, which demonstrated no statistical difference in the risk of SCRC free between PC patients undergoing RT and RP (p = 0.9766). Conclusion: Whether or not pelvic RT for PC is associated with an increased risk for SCRC on a population-based level remains a matter of considerable debate. From a clinical perspective, these PC survivors should be counseled accordingly and received continued cancer surveillance with regular colonoscopy follow-up.
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10.7150/jca.44726
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pubmed_475_17418
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There is still no well-established consensus about the clinical management of hydatidosis. Currently, surgery continues to be the first therapeutic option, although treatment with anti-parasitic drugs is indicated as an adjuvant to surgery to decrease the number of relapses and hydatid cyst size. When surgery is not possible, medical treatment is indicated. Traditionally, albendazole was used in monotherapy as the standard treatment. However, combined therapy with albendazole plus praziquantel appears to improve anti-parasitic effectiveness. To date, no safety studies focusing on such combined therapy have been published for the treatment of hydatidosis. In this work, we analyze the adverse effects seen in 57 patients diagnosed with hydatidosis who were treated with praziquantel plus albendazole combined therapy between 2006 and 2010.
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10.4269/ajtmh.13-0059
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pubmed_285_11598
|
OBJECTIVE
The aim of this study was to review the reliability and reproducibility of 3D-CBCT (cone beam computed tomography) cephalometric landmark identification.
METHODS
Electronic databases (Pubmed, Scopus, Web of Science) were searched for papers published from 1998 to October 2014. Specific strategies were developed for each database, with the guidance of a librarian. Two reviewers independently analyzed the titles and abstracts for inclusion. The articles that met the inclusion and exclusion criteria were selected for full-text reading, and the selected articles went through methodological quality evaluation. After the exclusion of repeated articles, the titles of the remaining ones were read and 1,328 of them were excluded. The abstracts of 173 articles were read, of which 43 were selected, read in full and submitted to the inclusion and exclusion criteria. Fourteen articles or studies with reliable methodology and reproducibility remained. The data were collected, organized into figures and analyzed for determination of the reliability and reproducibility of the three-dimensional cephalometric landmarks.
RESULTS
Overall, the landmarks on the median sagittal line and dental landmarks had the highest reliability, while the landmarks on the condyle, porion and the orbitale presented lower levels of reliability. Point S must be marked in the multiplanar views associated with visualization in 3D reconstruction. Further studies are necessary for evaluating soft tissue landmarks.
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pubmed_285_11598
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pubmed_700_15350
|
Twenty five adult patients with minimal changes disease proven at kidney biopsy and 13 of them older than 50 years of age are reported. Clinically, 32% of cases behaved as "impure" nephrotic syndrome, with no one case of established renal insufficiency; in nine cases, the process was antedated by a triggering event, usually infective episodes. In four cases who received no treatment, spontaneous remission was observed. All treated patients but one, initially responded to corticosteroid treatment in a period shorter than 1 month and 40% of patients presented maintained remission. There were no important complications derived from the disease nor from the treatment and at the end of the follow up only one patient died from a disease unrelated to the nephropathy.
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pubmed_700_15350
|
pubmed_842_25452
|
OBJECTIVE
Attention-deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) are the 2 most frequent psychiatric disorders co-occurring with Tourette syndrome (TS). Both usually cause greater impairment in psychosocial functioning than the tics themselves. In a previous study, we examined the relationship of attention-deficit/hyperactivity disorder to other comorbid conditions in TS. The relationship of OCD to other comorbidities in TS still remains unclear and is the focus of the present study.
METHODS
Pearson's χ tests and logistic regressions (year-wise) were used to examine a cross-sectional sample of children and adolescents (n = 5060) diagnosed with TS, taken from the Tourette Syndrome International Database Consortium. We explored the relationship of OCD to other comorbid conditions in TS across different age groups.
RESULTS
In children (ages 5-10 y) with TS, higher rates of comorbidities were found in the presence compared with the absence of OCD. Adolescents (ages 11-17 y) with TS + OCD showed higher rates of internalizing (i.e., anxiety and mood) disorders when compared with those with TS - OCD. A year-wise increase of coexisting mood disorders was found for subjects with TS with and without OCD.
CONCLUSIONS
Overall, children and adolescents with TS + OCD showed higher rates of comorbid disorders compared with those with TS - OCD. This underlines the necessity for a comprehensive assessment of additional comorbidities even if the 2 disorders (TS + OCD) have already been diagnosed.
|
10.1097/DBP.0b013e31823f6933
|
pubmed_40_4704
|
We demonstrate a biomimetic synthesis methodology that allows us to create Li2O-MgO-P2O5-TiO2 nanocrystalline glass with mesoporous structure at lower temperature. We design a 'nanocrystal-glass' configuration to build a nanoarchitecture by means of yeast cell templates self-assembly followed by the controlled in-situ biomineralization of materials on the cell wall. Electrochemically active nanocrystals are used as the lamellar building blocks of mesopores, and the semiconductive glass phase can act both as the 'glue' between nanocrystals and functionalized component. The Li2O-MgO-P2O5-TiO2 nanocrystalline glass exhibits outstanding thermal stability, high conductivity and wide potential window. This approach could be applied to many other multicomponent glass-ceramics to fabricate mesoporous conducting materials for solid-state lithium batteries.
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pubmed_40_4704
|
pubmed_817_17979
|
OBJECTIVE
To review our national cervical cancer screening program using existing Ministry of Public Health primary healthcare centers (PHCs) and report the impact of women's knowledge, attitude, behavior, and practices on screening uptake and outcome.
METHODS
A cross-sectional study on cervical cancer screening offered to sexually active Lebanese women aged 21 years and above visiting PHCs. Exclusions were history of complete hysterectomy, gynecologic cancers, and current pregnancy. Data were collected through a questionnaire and conventional cervical smear performed by trained healthcare providers and sent to one centralized cytopathology laboratory.
RESULTS
Of 12 273 eligible women, 1.7% had an abnormal cervical smear test including 161 atypical squamous cells (ASC) of undetermined significance, 6 atypical glandular cells of undetermined significance, 16 low-grade squamous intraepithelial lesion (SIL), 17 ASC-cannot rule out high-grade SIL, 11 high-grade SIL, and one invasive carcinoma. Knowledge and attitudes significantly affected participation in screening; women lacking awareness had rarely undergone a cervical smear.
CONCLUSION
In Lebanon, cytology-based cervical cancer screening is feasible within the PHCs. Positive screen incidence was low. Despite previous campaigns, a low level of knowledge persists, and affects women's com with the screening guidelines. Advocacy and awareness activities by key healthcare providers may help to improve participation.
|
10.1002/ijgo.14489
|
pubmed_1034_19625
|
Isostructural Zn(II)/Cd(II) mixed ligand coordination polymers (CPs) {[M(IPA)(L)]}n (CP1 and CP2) built from isophthalic acid (H2IPA) and 3-pyridylcarboxaldehyde nicotinoylhydrazone (L) were prepared using versatile synthetic routes: viz., diffusion of precursor solutions, conventional reflux methods, and green mechanochemical (grinding) reactions. Both robust CPs synthesized by different routes were characterized by various analytical methods, and their thermal and chemical stability as well as the phase purity was established. Crystallographic studies revealed that CP1 and CP2 are isostructural frameworks and feature a double-lined two-dimensional network composed of Zn2+/Cd2+ nodes connected through IPA and pillared by the Schiff base ligand L with a double-walled edge. The photoluminescent (PL) properties of CP1 and CP2 have been exploited as dual detection fluorosensors for hexavalent chromate anions (CrO42-/Cr2O72-) and 2,4,6-trinitrophenol (TNP) because it was observed that the emission intensity of aqueous suspensions of CPs selectively quenches by chromate anions or TNP among large pools of different anions or nitro compounds, respectively. Competitive experiments in the presence of interfering anions/other nitro compounds also revealed no major effect in the quenching efficiency, suggesting the selective detection of hexavalent chromate anions as well as TNP by the LCPs. The limits of detection by CP1 for CrO42-/Cr2O72- and TNP are 4 ppm/4 ppm and 28 ppb, respectively, whereas the limits of detection by CP2 for the same analytes are 1 ppm/1 ppm and 14 ppb, respectively. A probable mechanism for the quenching phenomena is also discussed.
|
10.1021/acs.inorgchem.6b02810
|
pubmed_158_19441
|
A patient with a large saphenous vein graft aneurysm is described. This case illustrates the role of magnetic resonance imaging and cardiac catheterization in patients with a mediastinal mass and history of coronary bypass surgery.
|
10.1016/s0002-9149(96)00852-1
|
pubmed_475_5884
|
OBJECTIVES
The purpose of this study was to assess intraosseous rotation as the third dimension of scaphoid anatomy on a 3D CT model using common volume rendering software to impact anatomical reconstruction of scaphoid fractures.
METHODS
CT images of 13 cadaver wrist pairs were acquired. Reference axes for the alignment of distal and proximal scaphoid poles were defined three-dimensionally. Two methods for rotation measurement-the reference axis method (RAM) and the scapho-trapezio-trapezoidal joint method (STTM)-were developed and compared by three independent observers.
RESULTS
Rotation measured by the RAM averaged 66.9° ± 7 for the right and 67.2° ± 5.8 for the left wrists. Using the STTM there was a mean rotation of 68.6° ± 6.6 for the right and 68.6° ± 6.8 for the left wrists. The overall results showed a significant variability of the measured values between different specimens (P < 0.05). There was no significant difference between left and right wrists of the same specimen, neither for the RAM (P = 0.268) nor for the STTM (P = 0.774). Repeatability coefficients between the observers were low, indicating good repeatability.
CONCLUSIONS
The presented methods are practical tools to quantify intraosseous rotation between distal and proximal scaphoid poles using common volume rendering software. For clinical application the opposite side provides the best reference values to assess malrotation in scaphoid fracture cases.
KEY POINTS
Scaphoid intraosseous rotation can be measured using common volume rendering software. The opposite uninjured side provides good reference values for rotation measurement. Assessment of malrotation may impact anatomical reconstruction of scaphoid fractures.
|
10.1007/s00330-014-3116-y
|
pubmed_636_11358
|
BACKGROUND
Histamine H(3) receptor antagonists have been considered as potential drugs to treat central nervous system diseases. However, whether these drugs can inhibit epileptogenesis remains unclear. This study aimed to investigate the effects of thioperamide, a selective and potent histamine H(3) receptor antagonist, on the seizure development and memory impairment induced by pentylenetetrazole (PTZ)-kindling epilepsy in rats.
METHODS
Chemical kindling was elicited by repeated intraperitoneal (ip) injections of a subconvulsant dose of PTZ (35 mg/kg) once every 48 hours for 12 times, and seizure activity of kindling was recorded for 30 minutes. Control rats were ip injected with saline instead of PTZ. Morris water maze was used to evaluate the spatial memory. Phosphorylated cyclic adenosine monophosphate response element binding protein (p-CREB) was tested by Western blotting in hippocampus.
RESULTS
Intracerebroventricular (icv) injections with thioperamide (10 µg, 20 µg) 30 minutes before every PTZ injections, significantly prolonged the onset of PTZ-kindling and inhibited the seizure stages. PTZ-kindling seizures led to the impairment of spatial memory in rats, and thioperamide ameliorated the impairment of spatial learning and memory. Compared to non-kindling rats, there was a significant decrease in p-CREB level in hippocampus of the PTZ-kindling rats, which was reversed by thioperamide.
CONCLUSIONS
Thioperamide plays a protective role in seizure development and cognitive impairment of PTZ-induced kindling in rats. The protection of thioperamide in cognitive impairment is possibly associated with the enhancement of CREB-dependent transcription.
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pubmed_636_11358
|
pubmed_1073_20690
|
Inflammatory immune activation has been frequently associated with the development of major depression. This association was confirmed in patients receiving long-term treatment with pro-inflammatory interferon-α (IFN-α). Microglia, the resident immune cells in the brain, might serve as an important interface in this immune system-to-brain communication. The aim of the present study was to investigate the role of microglia in an IFN-α mouse model of immune-mediated depression. Male BALB/c mice were treated with daily injections of IFN-α for two weeks. Depressive-like behavior was analyzed in the forced swim and tail suspension test. Activation of microglia was measured by flow cytometry. Pro-inflammatory M1 type (MHC-II, CD40, CD54, CD80, CD86, CCR7), anti-inflammatory M2 type (CD206, CD200R), and maturation markers (CD11c, CCR7) were tested, as well as the chemokine receptor CCR2. IFN-α led to a significant increase in depressive-like behavior and expression of the pro-inflammatory surface markers MHC-II, CD86, and CD54, indicating M1 polarization. Because IFN-α-treated mice showed great individual variance in the behavioral response to IFN-α, they were further divided into vulnerable and non-vulnerable subgroups. Only IFN-α vulnerable mice (characterized by their development of depressive-like behavior in response to IFN-α) showed an increased expression of MHC-II and CD86, while CD54 was similarly enhanced in both subgroups. Thus, IFN-α-induced activation of microglia was specifically associated with depressive-like behavior.
|
10.1016/j.bbi.2015.09.016
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pubmed_461_6392
|
To evaluate the effect of male contraceptive acceptance on fertility, the Danfa Family Planning Project in rural Ghana studied a sample of its male family planning acceptors. The findings show that half of the survey respondents accepted foam for use by their partners and half accepted the condom. The continuation rate (69 percent at 12 months) and use-effectiveness rate (80 percent at 12 months) reported by men were higher than those reported by women program acceptors. It is felt that men can play a significant role in affecting fertility through their influence on a couple's choosing to use contraception and as a result of their motivation to obtain contraception and see that it is used. It is urged that increasing emphasis be placed on providing family planning services for men in African programs.
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pubmed_461_6392
|
pubmed_708_23521
|
The Mr 63,000 membrane polypeptide (gp63) is one of the Leishmania receptors for host macrophages and has been shown to protect mice from infection. The gene encoding gp63, the major Mr 63,000 surface glycoprotein of L. major promastigotes, has been expressed as a fusion protein with the enzyme glutathione S- transferase encoded by the parasitic helminth Schistosoma japonicum. This fusion protein was recognized by polyclonal antibodies to the native Leishmania gp63 polypeptide. The insoluble gp63 fusion protein was purified by SDS-PAGE and electroelution and was used to raise antibodies in rabbits. These rabbit anti-gp63 antibodies recognized the fusion protein and the denatured parasite gp63 on immunoblots and by immunofluorescence on fixed promastigotes, but did not recognize the native molecule on live organisms. However, antibodies raised against native promastigote glycoproteins, affinity purified on solid-phase gp63 fusion protein, recognized both native and denatured gp63, suggesting the presence of native determinants in the recombinant protein. The gp63 fusion protein did not protect mice of either healer or nonhealer phenotype from challenge infection with live promatigotes. The implications of these results for the engineering of recombinant DNA-produced molecular vaccines are discussed.
|
10.1016/0014-4894(90)90127-x
|
pubmed_499_9557
|
INTRODUCTION
Opioids may be necessary for guideline-concordant acute perioperative pain management, but their use carries risks for unintended prolonged use and addiction. Guidelines recommend use of validated non-pharmacological pain care (NPPC) approaches in conjunction with prescribed opioids and other analgesics. Our protocol outlines a population-level, pragmatic trial that will test a bundled intervention comprised of an electronic health record (EHR) portal-based conversation guide, EHR clinical decision support (CDS), and a suite of self-management educational and support materials to encourage and advance NPPC use.
METHODS
We are conducting a stepped-wedge, cluster-randomized pragmatic trial spanning seven surgical specialties across six geographically diverse locations within the Mayo Clinic Enterprise. Thirty two surgical practices across six locations (Rochester, Minnesota; Mankato, Minnesota; La Crosse, Wisconsin; Eau Claire, Wisconsin; Phoenix, Arizona; Jacksonville, Florida) comprise 22 distinct practice clusters that are randomly assigned to one of five steps using constrained randomization. Steps "go live" by initiating the intervention at 7-month intervals between March 2021 and July 2023. Patients over 18 years of age who are scheduled for qualifying procedures within "live" consenting practices are sent a Healing After Surgery guide via their patient portals pre-operatively, directing them to identify their preferred NPPC modalities among 13 approaches. These selections create CDS options for care teams to support patients with self-management materials that reinforce safe NPPC use.
PLANNED OUTCOMES
Patients' clinical, demographic, and outcome data will be abstracted from the Epic EHR. Primary outcomes will be the Patient Reported Outcomes Measurement Information System (PROMIS) pain interference and physical functioning computer adaptive tests (CAT) collected at 1, 2, and 3 months postoperatively via the patient portal. We will mail printed versions of the 6-item PROMIS short forms to portal non-responders to minimize bias. Secondary outcomes will include the PROMIS anxiety CAT, opioid consumption, and self-reported NPPC use.
TRIAL REGISTRATION
ClinicalTrials.gov identifier, NCT04570371.
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10.1007/s40122-022-00393-x
|
pubmed_983_20629
|
OBJECTIVE
To investigate short- and long-term outcome following blunt trauma in pregnancy, and to identify risk factors for adverse pregnancy outcome in these cases.
METHODS
A retrospective cohort study of all pregnant women who were admitted following blunt trauma (N=411). Women who experienced immediate complications (N=13) were compared with those who did not (N=398). Pregnancy outcome of women who experienced trauma during pregnancy and did not deliver during the trauma admission (N=303) were compared with a control group of women matched to by maternal age and parity in a 3:1 ratio (N=909).
RESULTS
The overall rate of immediate complications was 3.2%, with the most common complications being preterm labor (2.0%) and placental abruption (1.7%). Independent risk factors for immediate complications were higher severity of trauma, multiple gestation, vaginal bleeding and uterine contractions at admission. Patients who experienced trauma were at increased risk for long-term adverse outcome including preterm labor, placental abruption, and perinatal morbidity. Increased trauma severity (ISS ≥ 5) and the need for laparotomy during the trauma hospitalization were independently associated with long-term adverse pregnancy outcome.
CONCLUSION
Trauma during pregnancy is associated with both immediate and long-term adverse pregnancy outcome. Women who experience trauma should be followed more closely throughout pregnancy.
|
10.3109/14767058.2011.648243
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pubmed_638_5274
|
A 63-year-old woman experienced progressive respiratory distress and psoriatic plaques. The radiographic images showed diffuse interstitial infiltrates. The surgical open lung biopsy revealed an obliteration of the alveolar spaces by plugs of connective tissue distributed within the terminal bronchioles, alveolar ducts and spaces. No relevant cause was determined, and she was diagnosed with idiopathic organising pneumonia. The patient was discharged with oral glucocorticosteroid and supplemental oxygen therapy. One month later, the patient's pulmonary status had progressively worsened, and she was re-admitted. She required higher oxygen concentrations and mechanical ventilation. Pharmacological therapy included high-dose steroids and cyclophosphamide. Serological assays revealed high antibodies titers (both IgM and IgG) to cytomegalovirus. Therefore, ganciclovir was added to the regimen. Despite the therapy, she died as a result of the disease. The review of the current literature on the topic is also presented.
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10.4081/monaldi.2007.489
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pubmed_143_20773
|
PURPOSE
To estimate how many boys with UDT must undergo orchiopexy to prevent one case of TC, one death from TC and one exposure to TC treatment beyond radical orchiectomy as compared to being treated at an older age.
METHODS
This retrospective study utilized data from a 2007 Swedish study of males who underwent orchiopexy for UDT (Pettersson et al.). TC incidence for boys undergoing orchiopexy for UDT was assessed based on the age at orchiopexy (0-6 years, 7-9 years, 10-12 years, 13-15 years). The incidence of TC in each age cohort was calculated and used to determine the number needed to treat (NNT) for each age group using assumptions based on published TC outcomes.
RESULTS
For an index patient ≤ 6 years, 372 boys need to undergo orchiopexy to prevent a single case of TC, 1488 boys to prevent exposure to TC therapy beyond radical orchiectomy, and 5315 boys to prevent a single TC-related death compared to treatment at an older age.
CONCLUSION
While there is evidence supporting benefits of early orchiopexy, the NNT to affect TC outcomes is very high. Even those with delayed orchiopexies have low risk for TC poor outcomes. This information can be used when counseling patients and families faced with UDT about the risks related to TC, especially with comorbidities.
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10.1007/s00345-019-03034-9
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pubmed_636_8551
|
Adderall (amphetamine, dextroamphetamine mixed salts), a widely prescribed stimulant for the treatment of attention-deficit/hyperactivity disorder in children and adolescents, is considered safe with due precautions. Nonmedical use of Adderall is prevalent and rising in high school and college students. Use of prescribed Adderall without intention to overdose as a cause of myocardial infarction is extremely rare, and to our knowledge, only 3 cases have been reported in the pediatric literature. We report a case of acute myocardial infarction in an adolescent without cardiovascular risk factors who took the total prescribed daily dose of Adderall one time while consuming alcohol. The sporadic use of Adderall with alcohol creates a potentially dangerous situation with serious cardiovascular adverse effects. We should have a high degree of suspicion for children and adolescents on stimulant therapy who present with chest pain and an abnormal electrocardiogram in the pediatric emergency department, and there is a need to evaluate them for myocardial ischemia and infarction.
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10.1097/PEC.0b013e31827b5663
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pubmed_760_1545
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The construct of complexity has been advanced recently as a potentially contributing variable in the efficacy of treatment for children with functional phonological disorders. Thus far, complexity has been defined in terms of linguistic and psycholinguistic structure, articulatory phonetic variables, and conventional clinical factors. The focus of this paper is on clinical complexity as it influences the selection of target sounds for treatment, with three clinical factors reviewed: consistency of the error, normative age of acquisition, and number of errors to be treated. The collective findings suggest that treatment of seemingly more complex targets results in greater phonological gains. These results are integrated with converging evidence from other populations and language and learning domains.
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10.1044/0161-1461(2001/021)
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pubmed_612_9244
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Genetically encoded fluorescent indicators of neuronal activity are ultimately developed to dissect functions of neuronal ensembles during behavior in living animals. Recent development of near-infrared shifted calcium and voltage indicators moved us closer to this goal and enabled crosstalk-free combination with blue light-controlled optogenetic tools for all-optical control and readout. Here I discuss designs of recent near-infrared and far-red calcium and voltage indicators, compare their properties and performance, and overview their applications to spectral multiplexing and in vivo imaging. I also provide perspectives for further development.
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10.1016/j.jneumeth.2021.109314
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pubmed_516_3490
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The structure of a new metastable geometric isomer of [Ru(NH3)4(H2O)(SO2)][MeC6H4SO3]2 in which the SO2 group is coordinated through a single oxygen in an eta1-OSO bonding mode has been determined at 13 K; the new isomer was obtained as a 36% component of the structure within a single crystal upon irradiation using a tungsten lamp.
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10.1039/b604039j
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pubmed_202_4591
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The authors provide a scheme of a comprehensive diagnosis of the aortic arch syndrome in nonspecific aortoarteritis. It includes the clinical and laboratory data together with the data on the anamnesis, angiography and ultrasound dopplerography. The derangement of the aortic arch was diagnosed in 65 (41%) out of 128 patients. There were 53 (81.5%) women and 12 (18.5%) men. The derangement of the branches of the aortic arch was most frequently (in 33.8% patients) associated with vasorenal hypertension syndrome. The use of modern research methods in combination with the clinical data and findings of objective examinations turned out fairly effective in the diagnosis of the derangement of the aortic arch in nonspecific aortoarteritis.
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pubmed_202_4591
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pubmed_1029_4097
|
Processing of M13 procoat protein, synthesized in a bacterial cell-free extract, to transmembrane coat protein by dog pancreas microsomes is stimulated by a system which is present in rabbit reticulocytes and depends on nucleoside triphosphates. This system consists of (at least) two components which act synergistically: members of the 70-kd heat shock protein family and (at least) one additional component. This component depends on ATP (or GTP) for its action.
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10.1002/j.1460-2075.1988.tb03144.x
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pubmed_381_1382
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In this paper, an in-depth study and analysis of landscape ecological planning and evaluation are carried out using the analytic hierarchy process (AHP) algorithm that integrates neural networks. The application of AHP in the field of tree species planning and the introduction of quantitative analysis methods can effectively change the subjectivity of previous qualitative analysis in tree species selection and make it objective, scientific, and reasonable. The research can provide a reference for other urban tree species planning. From the connotation of landscape ecological service process and ecological space structure, the analysis of landscape ecological service process involves service supply area and service association area, which correspond to different key components of ecological space structure. With the help of the platform, based on the identification and identification methods and theories of ecological spatial structure, the key components of ecological spatial structure in different environments are identified and extracted by using the representation model, binary suitability model, weighted suitability model, and process model. The type of service is based on the different service processes supported by the key components of the ecological spatial structure, forming the ecological spatial structure under different service types. Spatial structure; on this basis, the basic characteristics of the key components of the ecological spatial structure are analyzed, and the correlation characteristics of the ecological spatial structure are analyzed based on the correlation classification system of ecological spatial structure. A backpropagation (BP) neural network-based state assessment method of the grid structure is established. The method takes the parameters of the autoregressive model constructed by the acceleration signals of different working conditions as the feature quantity and the results of the fuzzy hierarchical analysis method as the labels, divides the data set into a training set and a test set, and uses the BP neural network learning method and the training set to supervised train the BP neural network learning assessment model. The test set is used to test the effectiveness and accuracy of the BP neural network-based learning method. The study shows that the evaluation system established by the BP neural network structure is fast and accurate and can substantially reduce the cost of manual testing.
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10.1155/2022/1926227
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pubmed_111_6711
|
A biracial sample of twenty-nine 14-yr old and thirty 16-yr old females was evaluated for zinc and copper nutritional status. Socioeconomic, demographic, anthropometric and 24-h dietary recall data were collected and plasma zinc and copper and erythrocyte zinc levels determined. Mean plasma zinc was 83 +/- 15 micrograms/dl; racial differences were significant (p less than 0.05) with plasma zinc levels at 87 +/- 3 micrograms/dl for whites and 79 +/- 3 micrograms/dl for blacks. Mean plasma copper was 119 +/- 24 micrograms/dl and was slightly higher for blacks than for whites. Mean erythrocyte zinc was 8.3 +/- 2.7 micrograms/g and represented 10 times the level of zinc in plasma. Plasma copper levels were positively (p less than 0.05) related to body size. Plasma copper was negatively (p less than 0.05) related to dietary fiber. Other dietary and economic factors did not affect mineral status.
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10.1093/ajcn/42.2.235
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pubmed_936_12881
|
The 2020s could be called, with little doubt, the "Mars decade". No other period in space exploration history has experienced such interest in placing orbiters, rovers and landers on the Red Planet. In 2021 alone, the Emirates' first Mars Mission (the Hope orbiter), the Chinese Tianwen-1 mission (orbiter, lander and rover), and NASA's Mars 2020 Perseverance rover reached Mars. The ExoMars mission Rosalind Franklin rover is scheduled for launch in 2022. Beyond that, several other missions are proposed or under development. Among these, MMX to Phobos and the very important Mars Sample Return can be cited. One of the key mission objectives of the Mars 2020 and ExoMars 2022 missions is the detection of traces of potential past or present life. This detection relies to a great extent on the analytical results provided by complementary spectroscopic techniques. The development of these novel instruments has been carried out in step with the analytical study of terrestrial analogue sites and materials, which serve to test the scientific capabilities of spectroscopic prototypes while providing crucial information to better understand the geological processes that could have occurred on Mars. Being directly involved in the development of three of the first Raman spectrometers to be validated for space exploration missions (Mars 2020/SuperCam, ExoMars/RLS and RAX/MMX), the present review summarizes some of the most relevant spectroscopy-based analyses of terrestrial analogues carried out over the past two decades. Therefore, the present work describes the analytical results gathered from the study of some of the most distinctive terrestrial analogues of Martian geological contexts, as well as the lessons learned mainly from ExoMars mission simulations conducted at representative analogue sites. Learning from the experience gained in the described studies, a general overview of the scientific outcome expected from the spectroscopic system developed for current and forthcoming planetary missions is provided.
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10.1016/j.aca.2021.339003
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pubmed_999_6673
|
Falls are a major health concern for older adults with Parkinson's disease (PD). This study was designed to examine differences in falls risk and its relation to changes in the average and variability (i.e. intra-individual variability) of reaction time (RT), finger tapping, standing balance and walking between healthy older adults and persons with PD. Thirty-nine adults with PD (70.0 ± 8.1 years) and 29 healthy older adults (66.8 ± 10.4 years) participated in this study. Falls risk (using the physiological profile assessment), gait, RT, balance and tapping responses were assessed for all persons. Results demonstrated that individuals with PD exhibited a greater risk of falling coupled with a general slowing of motor function covering declines in walking, RT and finger tapping. In addition, the movement responses of the PD group were more variable than the healthy older adults. Correlation results revealed group differences with regards to the neuromotor measures which were significantly correlated with falls risk. For the PD group, gait measures were highly correlated with their falls risk while, for the healthy older adults, falls risk was linked to balance measures even though PD persons had increased sway. Overall, persons with PD were at greater falls risk, moved slower and with increased variability compared to the healthy older adults. Further, while there are some similarities between the two groups in terms of those measures related to falls risk, there were also several differences which highlight that persons with PD can have different risk factors for falling compared to healthy adults of similar age.
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10.1007/s00221-021-06113-9
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pubmed_516_15686
|
Visual search can be facilitated when participants receive a preview of half the distractors (the preview benefit in search; Watson & Humphreys, 1997). Donk and Theeuwes (2001) have argued that preview-based benefits are abolished if the display items are isoluminant to a background. This is consistent with the preview benefit being due to onset capture by the new stimuli. In contrast, the present experiments challenge this suggestion and show that preview benefits can occur under isoluminant conditions, providing that they are given enough time to occur. In Experiment 1, we showed that a preview benefit can occur even with isoluminant stimuli, provided that the old items are previewed for a sufficient time. In Experiment 2, we tested and rejected the idea that this advantage is due to low-level sensory fatigue for the preview stimuli. These findings indicate that the preview effect is not caused solely by onset capture.
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10.3758/bf03193676
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pubmed_930_5449
|
The cleavage of factor B, a protein of the alternative pathway of complement, by kallikrein was studied. Like factor D, kallikrein can cleave B to generate the alternative pathway C3 convertase C3bBb. When this convertase was formed on erythrocytes previously coated with C3b, lysis was observed indicating that a functionally active C3 convertase was formed. B was also cleaved by kallikrein in the presence of fluid phase C3b, and this resulted in B fragments comparable in size to those generated in the presence of D. The capacity of kallikrein to cleave B is localised in the light chain of the kallikrein molecule, which is the same chain of kallikrein that is responsible for its other enzymatic activities. Since on a molar basis D is much more active then kallikrein in cleaving B, a physiological role for B activation by kallikrein is only likely under certain conditions, and still has to be established.
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10.1016/0049-3848(85)90182-3
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pubmed_1125_19720
|
Hereditary spastic paraplegia (HSP) is an extremely heterogeneous group of neurodegenerative disorders affecting the longest axons in the central nervous system. The most common genetic form accounting for about 40% of the autosomal-dominant HSP (ADHSP) cases is spastin gene, SPG4. We performed mutation screening of the spastin gene on 36 unrelated HSP patients from three different ethnic groups (Bulgarian, Turks and Gypsies) and found four new mutations and one already reported. The phenotype-genotype correlations in Bulgarian SPG4 patients showed a great difference in the age at disease onset between patients with missense mutations and those harboring deletions and splice-site mutations. Our study is the first to present corroborative clinical data in favor of the general hypothesis that the clinical course of the disease is related to the type of the spastin mutation. The clinical and genealogical findings in Bulgarian SPG4 patients suggest that a positive family history for inheritance as an autosomal-dominant trait is a strong indication for spastin mutation screening.
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10.1111/j.1399-0004.2006.00705.x
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pubmed_599_2678
|
We used atomic force microscopy to study dynamic forces between a rigid silica sphere (radius approximately 45 microm) and a silica nano-particle super-hydrophobic surface (SNP-SHS) in aqueous electrolyte, in the presence and absence of surfactant. Characterization of the SNP-SHS surface in air showed a surface roughness of up to two microns. When in contact with an aqueous phase, the SNP-SHS traps large, soft and stable air pockets in the surface interstices. The inherent roughness of the SNP-SHS together with the trapped air pockets are responsible for the superior hydrophobic properties of SNP-SHS such as high equilibrium contact angle (> 140 degrees) of water sessile drops on these surfaces and low hydrodynamic friction as observed in force measurements. We also observed that added surfactants adsorbed at the surface of air pockets magnified hydrodynamic interactions involving the SNP-SHS. The dynamic forces between the same silica sphere and a laterally smooth mica surface showed that the fitted Navier slip lengths using the Reynolds lubrication model were an order of magnitude larger than the length scale of the sphere surface roughness. The surface roughness and the lateral heterogeneity of the SNP-SHS hindered attempts to characterize the dynamic response using the Reynolds lubrication model even when augmented with a Navier slip boundary.
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10.1039/b901134j
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pubmed_926_22948
|
Many anticoagulant drugs inhibiting proteins of the coagulation cascade have been developed. The main targets of anticoagulant drugs are thrombin and factor Xa; inhibiting these factors delays thrombus growth, thus preventing thrombosis while increasing bleeding risk. A balance between thrombosis and bleeding is ensured in the 'therapeutic window' of the anticoagulant drug concentration range. Novel anticoagulant drugs and combinations thereof are being developed. We rank coagulation factors as potential anticoagulant drug targets in combination with thrombin inhibitors, aptamer HD1 and bivalirudin, providing a background for several promising dual target treatment strategies. The thrombin generation test was used to assess the whole coagulation cascade in normal and factor-deficient human blood plasma. Potential therapeutic windows were estimated for coagulation factors, ranking them as targets for anticoagulant drugs. Thrombin and factor Xa have been revealed as the most promising targets, which fully agrees with the current drug development strategy. Inhibitors of factors Va and VIIa are expected to have narrow therapeutic windows. Inhibitors of factors VIIIa and IXa are expected to have a moderate anticoagulant effect. Factors XI and XII are poor targets for anticoagulant drugs. Compared with plasma that is deficient in factor II, the thrombin inhibitors bivalirudin and aptamer HD1 had increased activity. Both inhibitors were tested in deficient plasma providing a model of potential drug combination. The most promising combinations were anti-thrombin with anti-V/Va and also anti-thrombin with anti-IX/IXa. Each combination had an incremental dose-effect dependence that is promising from the standpoint of the therapeutic window.
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10.1016/j.bbrep.2015.11.011
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pubmed_386_4511
|
BACKGROUND
The ABO blood subgroup A2 expresses lower levels of A antigen on the cell surface and is less immunogenic toward anti-A immunoglobulin present in blood type O or B recipients. Previous studies have shown successful kidney transplantation from A2 donors into O or B recipients with low pre-transplant anti-A titers. Previous studies suggest good results with recipient IgG titers <1:8. Few studies have specifically evaluated the importance of anti-A1 IgM titers on early outcomes following A2 to O or B kidney transplantation.
METHODS
We performed a single center, retrospective review of all A2 to O living donor kidney transplants. All recipients had pre-transplant anti-A IgG titers <1:8. IgM titers were measured in all recipients and were reported but not used to determine eligibility for transplant.
RESULTS
From 2001 to 2013, we performed seven consecutive A2 to O living donor kidney transplants. Early allograft dysfunction, acute rejection or thrombotic microangiopathy, occurred in four patients and were associated with high IgM titers despite low IgG titers.
CONCLUSIONS
Our data show a high incidence of early acute rejection or thrombotic microangiopathy in A2 to O kidney transplants with high recipient anti-A IgM titers despite low IgG titers. Steps to lower anti-IgM pre-transplant may reduce the risk of early allograft dysfunction in A2 to O or B kidney transplants. Attention should be paid to IgM titers in establishing individual center selection criteria for A2 to B kidney transplants under the new UNOS kidney allocation system.
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10.1111/ctr.12527
|
pubmed_738_24960
|
BACKGROUND & AIMS
The association between chronic inflammation and gastric carcinogenesis is well established, but it is not clear how immune cells and cytokines regulate this process. We investigated the role of interleukin 27 (IL27) in the development of gastric atrophy, hyperplasia, and metaplasia (preneoplastic lesions associated with inflammation-induced gastric cancer) in mice with autoimmune gastritis.
METHODS
We performed studies with TxA23 mice (control mice), which express a T-cell receptor against the H+/K+ adenosine triphosphatase α chain and develop autoimmune gastritis, and TxA23xEbi3-/- mice, which develop gastritis but do not express IL27. In some experiments, mice were given high-dose tamoxifen to induce parietal cell atrophy and spasmolytic polypeptide-expressing metaplasia (SPEM). Recombinant IL27 was administered to mice with mini osmotic pumps. Stomachs were collected and analyzed by histopathology and immunofluorescence; we used flow cytometry to measure IL27 and identify immune cells that secrete IL27 in the gastric mucosa. Single-cell RNA sequencing was performed on immune cells that infiltrated stomach tissues.
RESULTS
We identified IL27-secreting macrophages and dendritic cell in the corpus of mice with chronic gastritis (TxA23 mice). Mice deficient in IL27 developed more severe gastritis, atrophy, and SPEM than control mice. Administration of recombinant IL27 significantly reduced the severity of inflammation, atrophy, and SPEM in mice with gastritis. Single-cell RNA sequencing showed that IL27 acted almost exclusively on stomach-infiltrating CD4+ T cells to suppress expression of inflammatory genes.
CONCLUSIONS
In studies of mice with autoimmune gastritis, we found that IL27 is an inhibitor of gastritis and SPEM, suppressing CD4+ T-cell-mediated inflammation in the gastric mucosa.
|
10.1016/j.jcmgh.2020.04.014
|
pubmed_1140_24149
|
BACKGROUND
Beta2-agonists and glucocorticosteroids are two common treatments for COPD and they are often used in combination. Glucocorticosteroids mediate the anti-inflammatory response through the glucocorticosteroid receptors (GRs). Beta2-agonists are potent bronchodilators but they can have some anti-inflammatory properties by elevating the level of intracellular cAMP. In this study we aimed to investigate the anti-inflammatory effect of combination therapy in vitro.
METHODS
Neutrophils or the bilayer of endothelial and epithelial cells were preincubated with salbutamol, budesonide or budesonide followed by salbutamol. FMLP-induced IL-8, elastase release and neutrophil migration through the bilayer was measured.
RESULTS
Salbutamol at concentrations of 10(-4), 10(-5) and 10(-9) M inhibited IL-8, elastase release and migration of neutrophils in an inverse bell-shaped concentration-response manner. When given after budesonide (10(-9) and 10(-8)M), the inhibitory effect on migration was additive. This additive effect was not observed for elastase and IL-8 release.
CONCLUSIONS
Salbutamol inhibits neutrophil migration and IL-8 and elastase release in a concentration-dependent manner. Preincubation with low concentration of budesonide enhanced the inhibition of migration achieved by low concentrations of salbutamol.
|
10.1016/j.pupt.2005.01.006
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pubmed_207_3556
|
THE FACTORS RESPONSIBLE FOR EARLY OCCLUSION OF THE INFARCT VESSEL AFTER emergency percutaneous transluminal coronary angioplasty (PTCA) were retrospectively examined in 191 patients with acute myocardial infarction. During the 24-hour period after the initial balloon inflation, 47 patients (25%) had occlusion of the vessel (occlusion group), whereas 144 did not (nonocclusion group). The former patients immediately underwent repeat PTCA, which was successful in 37. Univariate correlates of early occlusion were a shorter time interval between the onset of symptoms and PTCA (3.5 +/- 2.2 vs 4.5 +/- 2.9 hours, p = 0.025), right coronary artery involvement (53% vs 30%, p = 0.015), prior thrombolytic therapy (49% vs 32%, p = 0.035), and undersized inflation (43% vs 17%, p < 0.001). With multivariate analysis the three independent predictors were undersized inflation (p < 0.001), right coronary artery involvement (p = 0.004), and a shorter time interval until PTCA (p = 0.011). Thus patients undergoing early PTCA and having right coronary artery involvement appear to be at greater risk of having early occlusion. Thrombolytic agents and undersized inflation may also play an important role in its development.
|
10.1016/0002-8703(93)90099-u
|
pubmed_265_18651
|
An expanding family of BCL-2 related proteins share homology, clustered within four conserved regions, namely BCL-2 homology (BH1-4) domains, which control the ability of these proteins to dimerize and function as regulators of apoptosis. Moreover, BCL-XL, BCL-2, and BAX can form ion-conductive pores in artificial membranes. The BCL-2 family, comprised of both pro-apoptotic and anti-apoptotic members, acts as a checkpoint upstream of CASPASES and mitochondrial dysfunction. BID and BAD possess the minimal death domain BH3, and the phosphorylation of BAD connects proximal survival signals to the BCL-2 family. BCL-2 and BCL-XL display a reciprocal pattern of expression during lymphocyte development. Gain- and loss-of-function models revealed stage-specific roles for BCL-2 and BCL-XL. BCL-2 can rescue maturation at several points of lymphocyte development. The BCL-2 family also reveals evidence for a cell-autonomous coordination between the opposing pathways of proliferation and cell death.
|
10.1146/annurev.immunol.16.1.395
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pubmed_729_5930
|
In contrast to our detailed knowledge of prokaryotic proteasomes, we have only a limited understanding of the prokaryotic regulators and their functional interaction with the proteasome. Most probably, we will soon learn more about the molecular structure and the mechanism of action of the prokaryotic regulators. Nevertheless, it still remains to be unravelled which signals or/and modifications transform an endogenous prokaryotic protein into a substrate of the proteasomal degradation machinery.
|
10.1007/978-3-642-59414-4_2
|
pubmed_1027_8781
|
The aim of this study was to determine the relative mobilisation of the different fatty acyl components of the triacylglycerol (TAG) of the chick embryo's adipose tissue in the light of the specific requirements of the developing neural tissues of the embryo for C20-22 polyunsaturated fatty acids. Pieces of adipose tissue, obtained from embryos at various developmental stages, were incubated in vitro in Dulbecco's Medium containing serum albumen. The fatty acid compositions of the initial tissue TAG and of the free fatty acid (FFA) mobilised from the tissue during 1 h of incubation were determined and compared. The composition of the FFA released into the medium under conditions of basal (i.e., unstimulated) lipolysis was markedly different in several respects from that of the TAG from which it originated. The polyunsaturated fatty acids, 20:4n-6, 20:5n-3, 22:5n-3 and 22:6n-3, were consistently found to be preferentially released into the medium, whereas the major fatty acyl constituents of the tissue, 16:0 and 18:1n-9, were selectively retained in the TAG. For example, at day 18 of development, the proportions (% w/w of fatty acids) of 20:5n-3 and 22:6n-3 released into the incubation medium were respectively 6.5 and 7.5 times higher than in the original tissue TAG. Glucagon stimulated the overall rate of mobilisation by approx. 2-fold and also partially suppressed the preferential mobilisation of C20-22 polyunsaturates. These results may be relevant to the elucidation of the means by which essential polyunsaturates are delivered from the yolk to the neural tissues of the embryo, with the implication of a mediatory role for the embryonic adipose tissue in this transfer.
|
10.1016/s0005-2760(97)00007-6
|
pubmed_362_196
|
Background
This report presents the findings of a simulation programme to improve the integrated response of teams working in mental health crisis (MHC) care. The programme consisted of the delivery of five interprofessional training courses that aimed to improve the core skills of teams working in MHC care.
Methods
Questionnaires were conducted pre-training and post-training, measuring participants' human factors using the Human Factors SKills for Healthcare Instrument, as well as self-reported learning experience using free text questions.
Results
The results found a significant change in human factors scores across all courses. Additionally, thematic analysis of the free text questions showed that participants identified improvements in communication, teamwork and clinical knowledge across all courses, with improvements in other skills in specific courses.
Conclusion
Overall, the findings suggest a positive impact of the simulation programme across a range of personal and clinical skills, developing further the case for including simulation training in routine mental healthcare education programmes. Future research should consider the long-term impact of interprofessional simulation training in MHC teams to gain further insight into the efficacy of this training modality.
|
10.1136/bmjstel-2020-000641
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pubmed_142_24576
|
Human ageing affects the immune system resulting in an overall decline in immunocompetence. Although all immune cells are affected during aging, the functional capacity of T cells is most influenced and is linked to decreased responsiveness to infections and impaired differentiation. We studied age-related changes in DNA methylation and gene expression in CD4+ and CD8+ T cells from younger and older individuals. We observed marked difference between T cell subsets, with increased number of methylation changes and higher methylome variation in CD8+ T cells with age. The majority of age-related hypermethylated sites were located at CpG islands of silent genes and enriched for repressive histone marks. Specifically, in CD8+ T cell subset we identified strong inverse correlation between methylation and expression levels in genes associated with T cell mediated immune response (LGALS1, IFNG, CCL5, GZMH, CCR7, CD27 and CD248) and differentiation (SATB1, TCF7, BCL11B and RUNX3). Our results thus suggest the link between age-related epigenetic changes and impaired T cell function.
|
10.1038/srep13107
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pubmed_565_23726
|
Using serological identification of recombinantly expressed tumor antigens (SEREX), we identified several autoantibodies against glioma-expressed antigens including GLEA1, GLEA2 and PHD-finger protein3 (PHF3). Analysing sera of 62 glioblastoma patients, we found an antibody response against GLEA1 in 15 sera (24.2%), against GLEA2 in 30 sera (48.4%) and against PHF3 in 35 sera (56.5%). Relating patient survival to the occurrence of autoantibodies against either GLEA1, GLEA2 or PHF3, we found a significant prolonged survival for glioblastoma patients positive for autoantibodies against GLEA2 (p = 0.0115) and PHF3 (p = 0.0031), respectively. The median survival of patients with GLEA2 antibodies was increased to 17.4 months and for patients with PHF3 antibodies to 14.7 months, as compared to 7.2 months for patients without GLEA2 or PHF3 antibodies. There was no significant correlation between patient survival and GLEA1-autoantibodies (p = 0.1611). Herein we present autoantibodies that are: (i) most frequent in glioblastoma patients; (ii) specific for glioblastoma-associated antigens; and (iii) significantly correlated with prolonged survival in patients with glioblastoma.
|
10.1002/ijc.20929
|
pubmed_463_5040
|
Bosutinib is one of five tyrosine kinase inhibitors commercially available in the United States for the treatment of chronic myeloid leukemia. This review of bosutinib summarizes the mode of action, pharmacokinetics, efficacy and safety data, as well as the patient-focused perspective through quality-of-life data. Bosutinib has shown considerable and sustained efficacy in chronic myeloid leukemia, especially in the chronic phase, with resistance or intolerance to prior tyrosine kinase inhibitors. Bosutinib has distinct but manageable adverse events. In the absence of T315I and V299L mutations, there are no absolute contraindications for the use of bosutinib in this patient population.
|
10.2147/PGPM.S32145
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pubmed_774_6366
|
OBJECTIVE
This study aimed to investigate whether maternal negative affectivity (MNA) moderates the effect of genetic polymorphism of SLC6A4 on behavior problems in children.
METHODS
Study participants comprised 143 preschoolers and their mothers from South Korea. The Childhood Behavior Checklist and Emotionality, Activity, and Sociability adult scale were used to measure child behavior and maternal affectivity. DNA from saliva was genotyped to determine serotonin transporter polymorphism.
RESULTS
MNA appeared to exert effects in externalizing (b =5.78, p＜0.001) and internalizing problems (b =6.09, p＜ 0.001). Interaction between SLCA4 polymorphism and MNA showed effects on externalizing (b =-7.62, p＜0.01) and internalizing problems (b =-9.77, p＜0.01). Children with two short alleles showed considerable differences in both externalizing and internalizing problems according to MNA; however, children with one short allele or none showed relatively few differences in behavior problems due to maternal affectivity.
CONCLUSION
The effect of SLC6A4 polymorphism on child behavior seemed to be moderated by MNA. In addition, the impact of MNA was found to vary based on a childs genetic risk. High MNA may trigger the risk allele while low MNA causes the risk allele to illicit less behavior problems. Children with two short variants of the SLC6A4 gene may benefit from intervention that modulates MNA.
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10.9758/cpn.2019.17.2.200
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pubmed_212_5216
|
Glomerular hemodynamics were studied, by micropuncture, in Munich-Wistar rats submitted to 24-hour bilateral ureteral ligation (BUL). Glomerular capillary pressure (PG), intratubular pressure (PT), and pressure in the first order peritubular capillaries (EAP) were measured with a servonulling device. Single nephron filtration fraction (SNFF) was calculated from arterial and peritubular blood protein concentrations. Single nephron glomerular filtration rate (SNGFR) was both measured by conventional micropuncture techniques and calculated from efferent arteriole blood flow and SNFF. Afferent arteriole blood flow (AABF) and resistance of afferent (Ra) and efferent (Re) arteriole were calculated. Measurements were repeated in the left kidney after releasing the ureter. Sham operated rats were used as control. BUL caused a fall in SNGFR (from 101.8 +/- 9.7 to 40.7 +/- [SEM] 6.0 nl/min/kg body wt), accounted for by a rise in PT (from 14.1 +/- 0.7 to 28.9 +/- 3.1 mm Hg), glomerular hemodynamics (particularly PG and AABF) being unchanged. A marked increase in Ra (from 6.6 +/- 0.7 to 10.8 +/- 1.5 dynes. sec. cm-5) occurred after releasing the ureter, lessening both PG and AABF. Therefore, a low SNGFR was maintained despite the concomitant normalization of PT.
|
10.1038/ki.1980.57
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pubmed_292_4521
|
The ecological importance of viruses is now widely recognized, yet our limited knowledge of viral sequence space and virus-host interactions precludes accurate prediction of their roles and impacts. In this study, we mined publicly available bacterial and archaeal genomic data sets to identify 12,498 high-confidence viral genomes linked to their microbial hosts. These data augment public data sets 10-fold, provide first viral sequences for 13 new bacterial phyla including ecologically abundant phyla, and help taxonomically identify 7-38% of 'unknown' sequence space in viromes. Genome- and network-based classification was largely consistent with accepted viral taxonomy and suggested that (i) 264 new viral genera were identified (doubling known genera) and (ii) cross-taxon genomic recombination is limited. Further analyses provided empirical data on extrachromosomal prophages and coinfection prevalences, as well as evaluation of in silico virus-host linkage predictions. Together these findings illustrate the value of mining viral signal from microbial genomes.
|
10.7554/eLife.08490
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pubmed_568_1398
|
Since 1987 the Swiss Working Group Interventional Cardiology of the Swiss Society of Cardiology coordinates the assessment of invasive diagnostic and therapeutic heart interventions across Switzerland. The aim of this report is to summarise the data for the year 2019, which was collected using a standardised questionnaire. In 2019, 37 centres performed a total of 57,975 coronary angiographies. In 48.2% of these cases a subsequent percutaneous coronary intervention was performed. Among a broad spectrum of structural heart interventions, we have observed a constant growth of transcatheter aortic valve implantations, and a total of 1912 transcatheter aortic valve implantations were performed in 2019.
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pubmed_568_1398
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pubmed_459_12660
|
We measured parathyrin (PTH) in peripheral venous blood samples and in thyroid veins (both homolateral and contralateral to the lesion) in 13 patients with surgically confirmed parathyroid adenomas. Two different RIAs were used, one specific to the mid-region of the molecule (44-68, M-PTH), the other specific to the carboxy-terminal region (65-84, C-PTH). With the M-PTH assay we established a statistically significant multiple correlation (P less than 0.05) between the PTH concentrations in blood from the peripheral and thyroid veins; no significant correlation was found when we used the C-PTH assay. Our results confirm the superiority of the M-PTH RIA over the C-PTH RIA for study of hormonal secretion in primary hyperparathyroidism.
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pubmed_459_12660
|
pubmed_311_8511
|
Identifying drug binding sites and elucidating drug action mechanisms are important components in a drug discovery process. In this review, we briefly compared three different approaches (sequence- based methods, structure-based methods and probe-based molecular dynamics (MD) methods) to identifying drug binding sites, and concluded that probe-based MD methods are much more advantageous in dealing with flexible target macromolecules and digging out druggable macromolecule conformations for subsequent drug screening. The applications of MD simulation to studying drug-target interactions were demonstrated with different types of target molecules, including lipid membrane, protein and DNA. The results indicate that MD simulations with enhanced sampling methods provide a powerful tool to determine free energy profiles/surfaces and identify important intermediate states, which are essential for the elucidation of drug action mechanisms. The future development of methods in MD simulations will benefit and speed up the drug discovery processes.
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10.2174/1568026619666181212102856
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pubmed_854_4821
|
We have collected evidences of a "transient site" for the local anesthetics (LA) lidocaine, etidocaine, bupivacaine and mepivacaine in sonicated egg phosphatidylcholine (EPC) vesicles. The effects of the uncharged anesthetic species at a fixed LA/EPC ratio inside the bilayer were measured by chemical shifts (C.S.) and longitudinal relaxation times (T(1)) of the lipid hydrogens. Two sort of changes were detected: (I) decrease, indicating specific orientation of the LA aromatic ring (measured as up-field C.S. changes by the short-range ring-current effect) and less rotational freedom (smaller T(1) values) for EPC hydrogens such as the two glycerol-CH(2) and the choline-CH(2) bound to the PO(4-) group, probably due to the nearby presence of the LA; (II) increase, indicating the aromatic ring is now perpendicular to the orientation observed before (causing down-field changes in C.S.) and larger T(1) values for all the choline and glycerol hydrogens, as a result of LA insertion behind these well-organized bilayer regions. The less hydrophobic, linear and nonlinear (lidocaine and mepivacaine, respectively) aminoamide analogs provide similar effects-described in I; their hydrophobic counterparts (etidocaine and bupivacaine) also produced comparable effects (depicted in II). The preferential positioning and orientation of each LA inside the bilayer is then determined by its hydrophobic and steric properties. We propose that this "transient site" in the lipid milieu exists also in biological membranes, where it can modulates the access of the uncharged LA species to its site(s) of action in the voltage-gated sodium channel.
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10.1016/j.bpc.2004.12.003
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pubmed_774_22665
|
Electrospray ionization mass spectrometry (ESI-MS) is an analytical technique that measures the mass of a sample through "soft" ionization. Recent years have witnessed a rapid growth of its application in noble-metal nanocluster (NC) analysis. ESI-MS is able to provide the mass of a noble-metal NC analyte for the analysis of their composition (n, m, q values in a general formula [Mn Lm ]q ), which is crucial in understanding their properties. This review attempts to present various developed techniques for the determination of the composition of noble metal NCs by ESI-MS. Additionally, advanced applications that use ESI-MS to further understand the reaction mechanism, complexation behavior, and structure of noble metal NCs are introduced. From the comprehensive applications of ESI-MS on noble-metal NCs, more possibilities in nanochemistry can be opened up by this powerful technique.
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10.1002/anie.201901970
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pubmed_76_15671
|
The usefulness of preoperative percutaneous transhepatic portal vein embolization (PTPE) in extending the indications for hepatectomy and increasing the safety of extended hepatectomy for hepatocellular carcinoma was studied in 21 patients who underwent right hepatic lobectomy with PTPE of the right first portal branch (group E), in 15 such patients but without PTPE (group N), and in seven such patients who underwent PTPE at this location but could not undergo surgery (group U). The mean volume of the left lobe increased but the results of a 15-minute indocyanine green retention test were worsened 2 weeks after PTPE and again 4 weeks after hepatectomy, but these changes after hepatectomy were almost the same in groups E and N. The worsening of liver function and coagulation test results was less in group E than in group N. The mean prognosis score was better in group E two weeks after PTPE than before, but not in group U. The four patients in group E with high portal vein pressure (> or = 30 cmH2O) or a high prognosis score (> or = 50 points) after PTPE developed hepatic failure after surgery. Preoperative PTPE was useful in extending the indications for hepatectomy and increasing the safety of extended hepatectomy. Evaluation of the clinical course after PTPE was also useful when decisions about the operative method to be used were being made.
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pubmed_76_15671
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pubmed_428_4565
|
Tropomyosin-related kinase receptor B (TrkB) has been observed to be a common player in posttraumatic stress disorder (PTSD) and the regulation of serum lipids levels. However, interplays of PTSD with TrkB on serum lipids levels have not been explored yet. This study was to investigate the interplays of PTSD and TrkB rs1187327 on serum lipid profiles. Variants of TrkB rs1187327 of 709 high school students were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analyses and verified by DNA sequencing. The PTSD Checklist Civilian Version (PCL-C) was used to assess PTSD. Colorimetric methods were used to determine the serum levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and glucose. The results show that the GG homozygotes had a significantly higher level of HDL-C than the A allele carriers of TrkB rs1187327 after the adjustment for gender, age and body mass index (BMI) (1.44 ± 0.299 mmol/L vs. 1.39 ± 0.266 mmol/L, p = 0.036). When PTSD was taken into account, the higher than the A allele carriers level of HDL-C of the GG homozygotes was observed significant after the adjustment for gender, age and BMI only in the subjects without PTSD (1.44 ± 0.293 mmol/ L vs. 1.39 ± 0.267 mmol/L, p = 0.030), but not in the subjects with PTSD. These results suggest that the A allele of TrkB rs1187327 may be associated with decreased levels of serum HDL-C in general healthy adolescents, but not in adolescents with PTSD.
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10.5582/bst.2017.01039
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pubmed_756_24332
|
BACKGROUND
Measurement of health-related quality of life (HRQoL) in dementia is difficult. At some point people with dementia become unable to meaningfully assess their own HRQoL. At such a point in time researchers need to rely on other types of information such as observation or assessments from informal caregivers (proxies). However, caregiver assessments may be biased by several mechanisms. The current study explores whether caregivers project part of their own HRQoL in their assessments of patient HRQoL.
METHODS
The participants in the current study were 175 pairs, consisting of community-dwelling persons with dementia and their caregivers. The EQ-5D, the EQ-VAS and the QoL-AD were administered to collect HRQoL measurements from patients and caregivers at baseline, 6 months and 12 months. Two linear mixed models were used to investigate factors that bias proxy ratings, one with the EQ-VAS as dependent variable, and one with the EQ-5D utility as dependent variable. The independent variables were caregiver age, caregiver sex and caregiver QoL-AD items.
RESULTS
The linear mixed model with EQ-VAS as dependent variable indicated that 3 caregiver characteristics, namely caregiver age, money (caregiver's financial situation) and valuation of life as a whole were significant predictors of the patient-by-proxy VAS scores. The linear mixed model with utility value as the dependent variable showed that caregiver age and valuation of the ability to do things for fun were significant predictors of the patient-by-proxy EQ-5D utility values.
CONCLUSIONS
The current study was a first step in identifying factors that bias patient-by-proxy HRQoL assessments. It was discovered that caregivers project part of their own HRQoL onto patients when assessing patient HRQoL. This implies that patient-by-proxy HRQoL values should be interpreted with caution and not be used as a direct substitute for patient self-assessment, even when patients are no longer able meaningfully assess themselves.
|
10.1186/1471-2288-13-110
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pubmed_157_7710
|
Bronchopulmonary dysplasia (BPD) is characterized by developmental arrest of the alveolar tissue. Oxidative stress is causally associated with development of BPD. The effects of hydrogen have been reported in a wide range of disease models and human diseases especially caused by oxidative stress. We made a rat model of BPD by injecting lipopolysaccharide (LPS) into the amniotic fluid at E16.5. The mother started drinking hydrogen-rich water from E9.5 and also while feeding milk. Hydrogen normalized LPS-induced abnormal enlargement of alveoli at P7 and P14. LPS increased staining for nitrotyrosine and 8-OHdG of the lungs, and hydrogen attenuated the staining. At P1, LPS treatment decreased expressions of genes for FGFR4, VEGFR2, and HO-1 in the lungs, and hydrogen increased expressions of these genes. In contrast, LPS treatment and hydrogen treatment had no essential effect on the expression of SOD1. Inflammatory marker proteins of TNFα and IL-6 were increased by LPS treatment, and hydrogen suppressed them. Treatment of A549 human lung adenocarcinoma epithelial cells with 10% hydrogen gas for 24 hr decreased production of reactive oxygen species in both LPS-treated and untreated cells. Lack of any known adverse effects of hydrogen makes hydrogen a promising therapeutic modality for BPD. Pediatr Pulmonol. 2016; 51:928-935. © 2016 Wiley Periodicals, Inc.
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10.1002/ppul.23386
|
pubmed_839_2396
|
OBJECTIVES
The effect of verapamil on tubular ischemia that is demonstrated by HIF-1alpha positivity in tubular cells following hyperoxaluria was evaluated in a rabbit model.
METHODS
Thirty-six healthy male rabbits were randomly divided into three groups. Animals in the hyperoxaluric group were fed with 0.75% ethylene glycol. The verapamil group was fed identically to the hyperoxaluric group. Additionally, the verapamil group received verapamil orally (0.1 mg/kg). The control group received no special diet. Six animals in each group were killed on the 7th day of the experiment and the remaining six at the 28th day. Kidneys of the rabbits were examined by histopathologic and immunohistochemical analysis to detect the presence and degree of HIF-1alpha positivity.
RESULTS
On the 7th day analysis, severe and moderate degree staining for HIF-1alpha in hyperoxaluric group were shown in four and two, respectively. In the verapamil group, however, three of six specimens showed nuclear staining (moderate in two and severe in one). Two of six specimens in the control group had minimal staining. The 28th day evaluation showed that two of the hyperoxaluric group had minimal degree nuclear staining but not in the remaining four. No staining was shown in the verapamil and control group animals.
CONCLUSIONS
Hyperoxaluria-related ischemia formation may be responsible for subsequent alterations in renal tubules. As a protective agent, verapamil was found to limit the presence of hypoxic changes as documented by HIF-1 alpha positivity in this study. These data also support the presence ischemic insult after hyperoxaluria induction in animal model.
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10.1007/s11255-009-9615-0
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pubmed_125_13278
|
COVID-19 pandemic in Argentina has affected the care of older adults with dementia deeply. Our objective was to study how the obligatory social isolation affected stress caregiver and burden of care of family members of subjects living with dementia in the community after the initial 4 weeks of quarantine in our setting. We did a questionnaire survey among 80 family caregivers of persons with Alzheimer's disease (AD) or related dementia collected on April 2020. We designed a visual analog scale to test the level of the burden of care. Characteristics of people with dementia and their caregivers were analyzed with descriptive (mean, standard deviation, frequency and percent) and inferential statistics (chi-square test). The sample included older adults (mean age: 80.51 ± 7.65) with different stages of dementia. Family was the primary provider of care in 65%. Overall, COVID-19 confinement increased stress caregiver independently of the dementia stage, but those caring for severe cases had more stress compared to milder forms of the disease. Other findings were that half of the subjects with dementia experienced increased anxiety and that most family members discontinued all sort of cognitive and physical therapies. Family members' main concerns were for severe dementia cases, fear of absence of the paid caregiver during the epidemic, and for mild cases fear of spreading the disease while assisting patients with instrumental activities. A partnership between departments of public health, care workers and families must be planned to guarantee continuity of care during these unique COVID-19 times.
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10.1017/S1041610220001593
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pubmed_540_11969
|
Mutations drive renal cell carcinoma biology and tumor growth. The BRCA1-associated protein-1 (BAP1) gene is frequently mutated in clear cell renal cell carcinoma (ccRCC) and has emerged as a prognostic and putative predictive biomarker. In this review, we discuss the role of BAP1 as a signature event of a subtype of ccRCC marked by aggressiveness, inflammation, and possibly a heightened response to immunotherapy.
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10.1016/j.humpath.2022.07.022
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pubmed_1091_10931
|
Purpose
To characterize the intraocular immune response following transplantation of iPS-derived allogeneic RPE cells into the subretinal space of non-immune-suppressed rhesus macaques.
Methods
GFP-labeled allogeneic iPS-derived RPE cells were transplanted into the subretinal space of one eye (n = 6), and into the contralateral eye 1 day to 4 weeks later, using a two-stage transretinal and transscleral approach. Retinas were examined pre- and post-surgery by color fundus photography, fundus autofluorescence, and optical coherence tomography (OCT) imaging. Animals were euthanized between 2 hours and 7 weeks following transplantation. T-cell (CD3), B-cell (CD20), and microglial (Iba1) responses were assessed immunohistochemically.
Results
Cells were delivered into the subretinal space in all eyes without leakage into the vitreous. Transplanted RPE cells were clearly visible at 4 days after surgery but were no longer detectable by 3 weeks. In localized areas within the bleb containing transplanted cells, T- and B-cell infiltrates and microglia were observed in the subretinal space and underlying choroid. A T-cell response predominated at 4 days, but converted to a B-cell response at 3 weeks. By 7 weeks, few infiltrates or microglia remained. Host RPE and choroid were disrupted in the immediate vicinity of the graft, with fibrosis in the subretinal space.
Conclusions
Engraftment of allogeneic RPE cells failed following transplantation into the subretinal space of rhesus macaques, likely due to rejection by the immune system. These data underscore the need for autologous cell sources and/or confirmation of adequate immune suppression to ensure survival of transplanted RPE cells.
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10.1167/iovs.17-22467
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pubmed_547_9727
|
Fertilization is triggered by sperm-egg interaction and fusion that initiate a transient rise(s) in the free intracellular calcium ([Ca(2+)](i)) that is responsible for a series of biochemical and cell biological events, so-called "egg activation". Calcium-dependent egg activation leads to the initiation of developmental program that culminates in the birth of individuals. A growing body of knowledge has uncovered the molecular mechanisms underlying sperm-induced transient [Ca(2+)](i) increase(s) to some extent; namely, in most animals so far studied, a second messenger inositol 1,4,5-trisphosphate (IP(3)) seems to play a pivotal role in inducing [Ca(2+)](i) transient(s) at fertilization. However, signaling mechanisms used by sperm to initiate IP(3)-[Ca(2+)](i) transient pathway have not been elucidated. To approach this problem, we have employed African clawed frog, Xenopus laevis, as a model animal and conducted experiments designed specifically to determine the role of the Src family protein-tyrosine kinases (SFKs or Src family PTKs) in the sperm-induced egg activation. This review compiles information about the use of PTK-specific inhibitors and activators for analyzing signal transduction events in egg fertilization. Specifically, we focus on molecular identification of Xenopus Src and the signaling mechanism of the Src-dependent egg activation that has been established recently. We also summarize recent advances in understanding the role of the Src family kinases in egg fertilization of other model organisms, and discuss future directions of the field.
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10.1016/j.bbapap.2003.11.017
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pubmed_389_16091
|
INTRODUCTION
Sleep deprivation has detrimental effects on cognitive processes, including decision making. The present study investigated how 72 h of sleep deprivation influenced individual neural performance in the Iowa gambling task using event-related potential technology.
METHODS
Eleven healthy male adults who participated in our study were randomized to be either in group with 72 h of social isolation condition or 72 h of sleep deprivation condition.
RESULTS
Results showed that, in the feedback stage, the N250-400 amplitude was smaller in post-test than in pre-test for the sleep deprivation condition, especially in the frontal cortex. No significant difference between the pre-test and post-test condition was found in the social isolation condition.
CONCLUSION
These results suggested that 72 h of sleep deprivation affected an individual's response to feedback stimuli, causing the individual to evaluate the stimuli slowly.
|
10.5152/npa.2016.12505
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pubmed_702_23409
|
Insulin secretion plays an essential part in the modulation of glucose homeostasis. Pancreatic beta cells are extremely sensitive to small changes in the concentration of glucose, peptides, hormones and fatty acids and insulin secretion is stimulated in response to these factors. The measurement of insulin secretion from isolated islets with either initiators or potentiators is a useful tool for investigating their efficacy in vitro without using cell lines, which can be subject to modification. Static islet incubation is a fast and powerful tool for the investigation of dose-response curves in response to insulin secretagogues, while islet perifusion experiments are useful for the investigation of the kinetics of insulin secretion. These two methods for measuring insulin secretion from isolated rodent islets of Langerhans are described in detail in this chapter.
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10.1007/978-1-59745-448-3_4
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pubmed_590_17288
|
The primary cilium is an antenna-like organelle that plays a vital role in organ generation and maintenance. It protrudes from the cell surface where it receives signals from the surrounding environment and relays them into the cell. These signals are then integrated to give the required outputs in terms of proliferation, differentiation, migration and polarization that ultimately lead to organ development and homeostasis. Defects in cilia function underlie a wide range of diverse but related human developmental or degenerative diseases. Collectively known as ciliopathies, these disorders present with varying severity and multiple organ involvement. The appreciation of the medical importance of the primary cilium has stimulated a huge effort into studies of the underlying cellular mechanisms. These in turn have revealed that ciliopathies result not only from defective assembly or organization of the primary cilium, but also from impaired ciliary signaling. This special edition of Organogenesis contains a set of review articles that highlight the role of the primary cilium in organ development and homeostasis, much of which has been learnt from studies of the associated human diseases. Here, we provide an introductory overview of our current understanding of the structure and function of the cilium, with a focus on the signaling pathways that are coordinated by primary cilia to ensure proper organ generation and maintenance.
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10.4161/org.28910
|
pubmed_1122_6407
|
Two sets of deprotection conditions have been evolved for the deprotection of oligodeoxyribonucleotides and their cleavage from commercially available cis -diol group-bearing universal polymer supports. In the first case, oligodeoxyribonucleotides anchored on the universal support were subjected to one of the standard deprotection conditions followed by treatment with aqueous 0.5 M sodium chloride + 0.2 M sodium hydroxide solution for 30 min at room temperature. In the second case, oligonucleotides bound to the universal support were treated with methanolic sodium hydroxide solution under microwave radiation to obtain fully deprotected oligomers within 4 min. Under both conditions, the cleavage of oligonucleotides from the support and their deprotection occurred quantitatively without any side product formation. The cleaved oligonucleotides were found to be identical in all respects (retention time on HPLC and biological activity in PCR) to the corresponding standard oligo-nucleotides.
|
10.1093/nar/27.10.e2
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pubmed_279_20456
|
The Cl- conductance of endoplasmic reticulum-enriched pancreatic microsomes was identified. Its regulation by nucleotides was investigated by measuring the rate of cation ionophore-induced microsome swelling in the presence of an inward Cl- gradient. The conductance was solubilized and reconstituted into liposomes. The Cl- conductance in intact microsomes was inhibited by stilbene (10(-4) M) and indanyloxyacetic acid (10(-5) M) derivatives. ATP increased Cl- conductance with half-maximal stimulation at 8 x 10(-6) M. Other trinucleotides (GTP, CTP and UTP) were without effect at 10(-4) M. The non-hydrolysable analogue of ATP, adenosine 5'-[beta gamma-methylene]triphosphate (AppCH2p) increased Cl- conductance with a potency similar to that of ATP. The same concentration of adenosine 5'-[gamma-thio]triphosphate (ATP gamma S) which is a substrate for kinases, had no effect. ATP stimulation of Cl- conductance was inhibited by stilbene derivatives. The data suggest the presence of at least one ATP-binding site, and show that the ATP does not need to be hydrolyzed and that its spatial conformation is important for activating the Cl- conductance. Solubilized microsomal proteins reconstituted into liposomes retained their stilbene-inhibited, ATP-stimulated Cl- conductance. A 167 kDa protein was detected by anti-CFTR antibodies in the intact microsomes, but not in the solubilized proteins. The 64 kDa protein (a component of a ubiquitous Cl- channel) was detected in the both intact and solubilized microsomes. These results suggest that this Cl- conductance is not a CFTR protein.
|
10.1016/0005-2736(93)90264-z
|
pubmed_960_7118
|
(1) Topiramate carries a dose-dependent risk of severe metabolic acidosis in adults and children. (2) Various situations increase the risk, including diarrhea, respiratory disorders and surgery. (3) Loss of appetite, fatigue and hyperventilation are warning signs.
|
pubmed_960_7118
|
pubmed_475_23100
|
Although risky/harmful drinking, in the form of binge drinking, remains a national problem, only recently have health services in universities systematically screened for drinking, drug use, and smoking. This article recounts "lessons learned" in two nurse-directed, interdisciplinary health services, which adapted the National College Depression Partnership model to include screening and brief intervention (SBIRT) for risky/harmful alcohol use in the form of binge drinking. Using a planned change model, nurse leaders worked with university administrators, providers, and health service staff to screen all students seeking health services for risky drinking. The outcomes suggest that this process may increase staff and student awareness of the importance of alcohol consumption to health, show the ease of using SBIRT screening along with standard screening tools, and yield information on the normalization of high-risk drinking in collegiate settings. Project findings indicate that common perceptions in college students minimize negative outcomes and stress the importance of additional quality assurance initiatives that review the efficacy of combinations of standardized screening tools.
|
10.1097/JAN.0b013e31828768cb
|
pubmed_987_16037
|
The global standard therapy for chronic myeloid leukemia (CML) is tyrosine kinase inhibitors (TKIs). One of the causes of therapeutic resistance to some TKIs corresponds to point mutations in the BCR-ABL1 fusion gene. Allogeneic hematopoietic cell transplantation (HCT) is a treatment option for high-risk CML, including TKI resistance. Although BCR-ABL1 point mutations comprise a major factor in the assessment of the indications for HCT, there is limited evidence for their significance in relation to transplant outcomes. This study aimed to evaluate the profiles and transplant outcomes of BCR-ABL1 mutations in allografted patients with CML. The retrospective study used a nationwide registry data including adult patients with CML who underwent their first HCT between 2006 and 2016. The inclusion criterion was the evaluation of the status of the BCR-ABL1 mutation before HCT. The cohort included 315 patients with a median age of 44 years (range 16-70 years). Point mutations were detected in 152 patients, of which 101 (66%) harbored T315I mutations and 51 harbored mutations other than T315I (non-T315I). With a median follow-up period of 38 months (range 2-114 months), overall survival (OS) at 3 years was worse in the mutation group than in the no-mutation group (53% versus 71%; P = .002), which was validated by multivariate analysis (hazard ratio [HR] = 1.50; 95% confidence interval [CI], 1.0-2.2; P = .038); this difference was remarkable in the chronic phase of CML. OS in the non-T315I group was significantly worse than that in the no-mutation group (HR = 1.69; 95% CI, 1.0-2.8; P = .035). The nationwide study has successfully evaluated the BCR-ABL1 mutational profile and its outcomes in patients with CML who received HCT. The mortality risk was significantly higher in patients with the BCR-ABL1 mutation than in patients without the mutation. These findings would be useful to understand the clinical significance of various BCR-ABL1 mutations in CML and provide insight into the on mid need for treatment strategies for cases of CML with BCR-ABL1 mutations.
|
10.1016/j.jtct.2022.03.009
|
pubmed_245_23462
|
Tuberous and tubular breast deformity are well-recognized abnormalities in the plastic surgery community that incur severe physical and psychological consequences in affected patients. Current reconstructive options for the tuberous and tubular breasts favor the use of prosthetic implants and soft-tissue manipulation. We present a case of tuberous and tubular breast deformity treated with a central mound reduction technique and mastopexy with imbricating sutures without the use of prosthetic implants. The patient remained extremely pleased with her results at long-term follow-up. This represents a unique case of successful reconstruction in a patient with a tuberous and tubular breast deformity using a central mound reduction technique with mastopexy and without a prosthetic device.
|
10.1097/GOX.0000000000001545
|
pubmed_1037_2243
|
The exploration of mechanochemical reactions has brought new opportunities for the design of functional materials. We synthesized the novel organic peroxide mechanophore bis(9-methylphenyl-9-fluorenyl) peroxide (BMPF) and examined its mechanochromic properties. The mechanism behind its mechanofluorescence was clarified and harnessed in polymer networks that can release the small fluorescent molecule 9-fluorenone upon exposure to a mechanical stimulus. Additionally, polymer networks cross-linked with BMPF units are able to tolerate temperatures up to 110 °C without any change in optical properties or mechanical strength. As mechanophores based on organic peroxide have rarely been documented so far, these fascinating results suggest excellent potential for applications of BMPF in stress-responsive materials. The mechanochemical protocol demonstrated here may provide guiding principles to expand the field of mechanochromic peroxides.
|
10.1021/jacs.1c08533
|
pubmed_891_18191
|
Objective Palliative care has played a key role in the response to the coronavirus disease 2019 (COVID-19) pandemic in Australia. This review of consecutive patients with COVID-19 referred to the palliative care consultancy service of a tertiary health service in Melbourne describes the palliative care experience with COVID-19 in Australia. Methods The experiences of 55 patients (median age 86 years; interquartile range (IQR) 81-90 years; 55% male; median Charlson comorbidity score 6 (IQR 5-8); 85% with Australia-modified Karnofsky Performance Status ≤50; 67% from residential aged care facilities) were reviewed to collect relevant data points. Results Most patients were referred for end-of-life care with symptoms including dyspnoea (80%) and agitation/delirium (60%). Continuous subcutaneous infusions were commenced in 71% of patients, with the most frequent medications being opioids and benzodiazepines in relatively small doses; 81% required ≤20 mg subcutaneous morphine equivalent and 64% required ≤10 mg subcutaneous midazolam over 24 h. Fifty patients (91%) died in hospital and the median time from palliative care referral to death was 3 days (IQR 1-5 days). Five patients were discharged back to residential aged care facilities. Overall, 80% of referrals were from the aged care team. Conclusion Our patients had similar demographics, symptoms, medication needs and outcomes to patients in similar settings overseas. We found the symptom management of patients with COVID-19 to be generally straightforward. However, the psychosocial needs of patients were predominant and contributed to complexity. This study highlights the need for well-integrated relationships between the palliative care consultancy service and the diverse range of key treating teams involved in the delivery of pandemic health care. What is known about the topic? Palliative care has played a key role in the response to the COVID-19 pandemic in Australia. There is limited research describing the Australian palliative care experience with the COVID-19 pandemic. What does this paper add? Patients with COVID-19 referred to a hospital-based palliative care consultancy service in Australia had similar demographic characteristics, symptoms, medication needs and outcomes to patients with COVID-19 referred to other palliative care services in the UK and the US. There were significant psychosocial issues affecting patients, families and staff in the context of the pandemic. What are the implications for practitioners? This study highlights the need for well-functioning working relationships between the palliative care consultancy service and other hospital teams that can be leveraged at a time of crisis, such as a pandemic, to provide optimal palliative care to patients.
|
10.1071/AH21157
|
pubmed_768_20143
|
The Medical Act of 1858 was the culmination of medical, political and social wrangling for several decades before its passage. This essay looks to place the Act in its correct historical context and will specifically consider whether it brought about unity to what was a disparate and factional profession. That it was an important piece of legislation in the history of British healthcare is unquestioned, but the extent to which it directly brought about change is more uncertain. In order to understand the background, content and repercussions of the Act, one must recognize the structure of the medical system at that time. One reason for doing this, as argued by some, is that the Medical Act, like the Apothecaries Act of 1815, was the result of changes to the profession and not the cause of them. Reformists hoped that the Medical Act would unify the profession, yet significant historical, hierarchical and political barriers stood in the way of reform.
|
10.1258/jmb.2012.012005
|
pubmed_957_10023
|
Liquid-liquid phase separation provides a versatile approach to fabricating cell-mimicking coacervates. Recently, it was discovered that phase separation of single-stranded DNA (ssDNA) allows for forming protocells and microgels in multicomponent systems. However, the mechanism of the ssDNA phase separation is not comprehensively understood. Here, we present mechanistic insights into the metal-dependent phase separation of ssDNA and leverage this understanding for a straightforward formation of all-DNA droplets. Two phase separation temperatures are found that correspond to the formation of primary nuclei and a growth process. Ca2+ allows for irreversible, whereas Mg2+ leads to reversible phase separation. Capitalizing on these differences makes it possible to control the information transfer of one-component DNA droplets and two-component core-shell protocells. This study introduces new kinetic traps of phase separating ssDNA that lead to new phenomena in cell-mimicking systems.
|
10.1002/anie.202208951
|
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