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1.
Zhonghua Er Ke Za Zhi ; 59(6): 459-465, 2021 Jun 02.
Artigo em Chinês | MEDLINE | ID: mdl-34102818

RESUMO

Objective: To analyze the clinical features, genetic characteristics, treatment and follow-up results of patients with hydrocephalus caused by methylmalonic acidemia combined with homocysteinuria, and to discuss the optimal strategies for assessing and treating such patients. Methods: From January 1998 to December 2020, 76 patients with hydrocephalus due to methylmalonic acidemia combined with homocysteinuria in the Department of Pediatrics in 11 hospitals including Peking University First Hospital were diagnosed by biochemical, genetic analysis and brain imaging examination. The patients were divided into operation-group and non-operation-group according to whether they underwent ventriculoperitoneal shunt. The clinical features, laboratory examinations, genotype, and follow-up data were retrospectively analyzed. Data were compared between the two groups using rank sum test, and categorical data were compared using χ2 test. Results: Among the 76 patients (51 male, 25 female), 5 were detected by newborn screening, while 71 were diagnosed after clinical onset, 68 cases (96%) had early-onset, 3 cases (4%) had late-onset. The most common clinical manifestations of 74 cases with complete data were psychomotor retardation in 74 cases (100%), visual impairment in 74 cases (100%), epilepsy in 44 cases (59%), anemia in 31 cases (42%), hypotonia or hypertonia in 21 cases (28%), feeding difficulties in 19 cases (26%) and disturbance of consciousness in 17 cases (23%). Genetic analysis was performed in 76 cases, all of whom had MMACHC gene variations, including 30 homozygous variations of MMACHC c.609G>A. The most common variations were c.609G>A (94, 62.7%), followed by c.658_660del (18, 12.0%), c.567dupT (9, 6.0%) and c.217C>T (8, 5.3%). Therapy including cobalamin intramuscular injection, L-carnitine and betaine were initiated immediately after diagnosis. A ventriculoperitoneal shunt operation was performed in 41 cases (operation group), and 31 patients improved after metabolic intervention (non-operation group). There was no significant difference in the age of onset, the age of diagnosis, the blood total homocysteine, methionine, and urinary methylmalonic acid concentration between the two groups (all P>0.05). The symptoms of psychomotor development, epilepsy, and visual impairments improved gradually after a long-term follow-up in the operation group. Conclusions: Hydrocephalus is a severe complication of methylmalonic acidemia combined with homocysteinuria. The most common clinical manifestations are psychomotor retardation, visual impairment, and epilepsy. It usually occurs in early-onset patients. Early diagnosis and etiological treatment are very important. Hydrocephalus may improve after metabolic intervention in some patients. For patients with severe ventricular dilatation, prompt surgical intervention can improve the prognosis.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos , Hidrocefalia , Erros Inatos do Metabolismo dos Aminoácidos/complicações , Erros Inatos do Metabolismo dos Aminoácidos/genética , Criança , Feminino , Humanos , Hidrocefalia/genética , Hidrocefalia/cirurgia , Recém-Nascido , Masculino , Ácido Metilmalônico , Oxirredutases , Estudos Retrospectivos
2.
Contemp Clin Trials ; 107: 106462, 2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34082074

RESUMO

Background Opioid analgesics are frequently initiated for chronic and acute pain despite weak evidence of benefit, although prescribing rates of some analgesics decreased in the context of the epidemic. In some populations, up to a quarter of opioid naïve persons prescribed opioids for non-cancer pain develop prescription opioid use disorder (OUD). Audit and feedback interventions rely on constructive use of routinely collected data to align professional behaviours and clinical practice with best evidence. These interventions have been shown to help reduce inappropriate initiation. However, effectiveness and acceptability of individualized "portraits" of physicians' prescribing patterns, to reduce inappropriate initiation of opioid analgesics to opioid naïve persons, have not been evaluated. Methods REDONNA is a mixed-methods randomized study testing the effectiveness of individualized prescribing Portraits to reduce inappropriate initiation of opioid analgesics. This intervention to improve safety of opioid prescribing in primary care in British Columbia (BC), Canada involves mailing individual prescribing portraits to an 'early group' of 2604 family physicians, followed in 6 months by a mailing to 2553 family physicians in the 'delayed group'. Primary outcome is number of new opioid prescriptions initiated in opioid naïve people, measured using administrative data from a centralized medication monitoring database covering all prescription opioids dispensed from BC community pharmacies. Secondary endpoints will compare prescribing impact between the two groups. A qualitative sub-study will examine feasibility among a purposive sample of physicians and patients. Discussion This trial provides important evidence on the intervention's potential to steer policy and practice on inappropriate opioid analgesics initiation. Trial registration: The study was registered prospectively on 30 March 2020 at the ISRCTN Register (https://www.isrctn.com/ISRCTN34246811).

3.
Mol Genet Genomic Med ; : e1691, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33943042

RESUMO

BACKGROUND: Pineal cyst is a benign lesion commonly occurring in people of any age. Until now, the underlying molecular alterations have not been explored. METHODS: We performed whole exome sequencing of 93 germline samples and 21 pineal cyst tissue samples to illustrate its genetic architecture and somatic mutations. The dominant and recessive inheritance modes were considered, and a probability was calculated to evaluate the significance of variant overrepresentation. RESULTS: By analyzing pineal cyst as a Mendelian disease with a dominant inheritance pattern, we identified 42,325 rare germline variants, and NM_001004711.1:c.476A>G was highly enriched (FDR<0.2). By analyzing it as a recessive disorder, we identified 753 homozygous rare variants detected in at least one pineal cyst sample each. One STIM2 rare variant, NM_001169117.1:c.1652C>T, was overrepresented (FDR<0.05). Analyzing at a gene-based level, we identified a list of the most commonlymutated germline genes, including POP4, GNGT2 and TMEM254. A somatic mutation analysis of 21 samples identified 16 variants in 15 genes, which mainly participated in the biological processes of gene expression and epigenetic regulation, immune response modulation, and transferase activity. CONCLUSION: These molecular profiles are novel for this condition and provide data for investigators interested in pineal cysts.

4.
Technol Health Care ; 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33998562

RESUMO

BACKGROUND: Early diagnosis of Alzheimer's disease (AD) remains challenging. It is speculated that structural atrophy in white matter tracts commences prior to the onset of AD symptoms. OBJECTIVE: We hypothesize that disruptions in white matter tract connectivity precedes the onset of AD symptoms and these disruptions could be leveraged for early prediction of AD. METHODS: Diffusion tensor images (DTI) from 52 subjects with mild cognitive impairment (MCI) were selected. Subjects were dichotomized into two age and gender matched groups; the MCI-AD group (22 subjects who progressed to develop AD) and the MCI-control group (who did not develop AD). DTI images were anatomically parcellated into 90 distinct regions ROIs followed by tractography methods to obtain different biophysical networks. Features extracted from these networks were used to train predictive algorithms with the objective of discriminating the MCI-AD and MCI-control groups. Model performance and best features are reported. RESULTS: Up to 80% prediction accuracy was achieved using a combination of features from the 'right anterior cingulum' and 'right frontal superior medial'. Additionally, local network features were more useful than global in improving the model's performance. CONCLUSION: Connectivity-based characterization of white matter tracts offers potential for early detection of MCI-AD and in the discovery of novel imaging biomarkers.

5.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(3): 352-357, 2021 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-33849825

RESUMO

OBJECTIVE: To establish animal models epidermal growth factor receptor inhibitor-related skin rashes using cetuximab, gefitinib or erlotinib. OBJECTIVE: Female SCID mice were randomly divided into blank control group and high-, moderate-, and low-dose cetuximab groups. The mice in control group received intraperitoneal injection of saline, and those in the 3 cetuximab groups were injected with 80, 40, and 20 mg/kg cetuximab (3 times a week for 4 weeks), respectively. The general skin appearance and skin pathologies of the mice were observed. Female BN rats were randomly divided into blank group, ovalbumin group, gefitinib group and erlotinib group, and in the latter 3 groups, the rats were given ovalbumin (1 mg), gefitinib (37.5 mg/kg), and erlotinib (23.5 mg/kg) by lavage once daily for 45 days, respectively. Skin pathologies of the rats were observed, and serum levels of TNF-α, IL-6 and other inflammatory factors were detected using ELISA. OBJECTIVE: Intraperitoneal injection of cetuximab did not induce typical skin rashes, scabs or obvious skin inflammation in the mice. In female BN rats, lavage of gefitinib caused obvious skin rashes, scabs and exudation, and obvious inflammatory cell infiltration, keratinosis, spinous layer release and epidermal thickening were observed in the skin. No obvious skin inflammation were observed in the rats in the control, ovalbumin or erlotinib groups. While IgE (P=0.061) and TNF-α concentrations (P=0.057) did not differ significantly among the groups, serum levels of IL-6 was significantly higher in gefitinib group than in the blank control group (P=0.016) but similar between erlotinib group and the blank group (P=0.910). OBJECTIVE: Intraperitoneal injection of cetuximab can not induce epidermal growth factor receptor inhibitor-related skin rashes in SCID mice. Lavage of gefitinib, but not erlotinib, can be used to establish models of epidermal growth factor receptor inhibitor-related rashes in BN rats.


Assuntos
Receptores ErbB , Neoplasias Pulmonares , Animais , Cloridrato de Erlotinib/toxicidade , Feminino , Camundongos , Camundongos SCID , Modelos Animais , Quinazolinas/toxicidade , Ratos
6.
Zhonghua Yi Xue Za Zhi ; 101(15): 1071-1076, 2021 Apr 20.
Artigo em Chinês | MEDLINE | ID: mdl-33878834

RESUMO

Objective: To investigate the clinical efficacy and safety analysis of bronchial thermoplasty (BT) in the treatment of severe asthma and asthma-chronic obstructive pulmonary disease overlap. Methods: The clinical data of 49 patients with asthma-COPD overlap who received BT in the University of Chinese Academy of Sciences Shenzhen Hospital from January 2016 to December 2018 and 50 patients with severe asthma who received BT in the same period were retrospectively analyzed. Patients were divided into overlap group and asthma group, and the baseline data of two groups were recorded. The pulmonary function before and after treatment (including forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), FEV1 as a percentage of predicted value (FEV1% pred)), hormone consumption, asthma control test (ACT) score, asthma quality of life questionnaire (AQLQ) score, asthma control questionnaire (ACQ) score, the overlap group before and after treatment COPD assessment test (CAT) score, modified British Medical Research Council (mMRC) score and postoperative respiratory adverse events in the next 3 weeks were comparatively analyzed. Results: The general baseline characteristics of the two groups are compared. The patients in the overlap group were older than those in the asthma group, and the course of disease and smoking history were longer than those in the asthma group. The inhaled hormone dosage in asthma group was greater than those in the overlap group ((64±11) years vs (48±11) years; 10.00 (10.00, 25.00) years vs 9.00 (1.75, 20.00) years; 20.00(2.00, 40.00) years vs 0 (0, 10.00) years; 320 (320, 640) µg/d vs 960 (320, 960) µg/d) (all P<0.05). The predicted values of lung function indexes FVC, FEV1, FEV1% pred in the overlap group before treatment were all lower than those in the asthma group (1.98 (1.43, 2.43) L vs 2.54 (2.02, 3.15) L; 0.92 (0.61, 1.26) L vs 1.69(1.17, 2.16) L; (50±16) L vs (65±14) L) (all P<0.05). There were no significant differences in ACT, ACQ, and AQLQ scores between the two groups before treatment (all P>0.05). Within 3 months after treatment, except for no significant improvement in FEV1% predicted value and inhaled hormone dosage in the overlap group (all P>0.05), other indexes in both groups were improved compared with those before treatment (all P<0.05). After 1 year of treatment, all indexes of the two groups were significantly improved than those before treatment, and all indexes of the asthma group were better than those of the overlap group (all P<0.05). In terms of respiratory adverse events occurring within 3 weeks after the operation, the incidence of cough and bloody sputum in the overlap group was higher than that in the asthma group, while the incidence of sputum and short-term wheezing was lower than that in the asthma group (all P<0.05). There were no statistically significant differences in the incidence of chest tightness, chest pain, segmental atelectasis and pneumonia between the two groups (all P>0.05), and the postoperative adverse reactions could be effectively controlled in a short period of time. Conclusion: BT treatment could not only improve the lung function, clinical symptoms and quality of life of asthmatic patients, but was also effective for asthma-COPD overlap patients. However, BT treatment had more benefits for asthmatic patients without serious adverse events occurred.


Assuntos
Asma , Termoplastia Brônquica , Doença Pulmonar Obstrutiva Crônica , Volume Expiratório Forçado , Humanos , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento
7.
J Phys Chem Lett ; : 4211-4217, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33900762

RESUMO

We report two novel roaming pathways for the H + C2H2 → H2 + C2H reaction by performing extensive quasiclassical trajectory calculations on a new, global, high-level machine learning-based potential energy surface. One corresponds to the acetylene-facilitated roaming pathway, where the H atom turns back from the acetylene + H channel and abstracts another H atom from acetylene. The other is the vinylidene-facilitated roaming, where the H atom turns back from the vinylidene + H channel and abstracts another H from vinylidene. The "double-roaming" pathways account for roughly 95% of the total cross section of the H2 + C2H products at the collision energy of 70 kcal/mol. These computational results give valuable insights into the significance of the two isomers (acetylene and vinylidene) in chemical reaction dynamics and also the experimental search for roaming dynamics in this bimolecular reaction.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33902273

RESUMO

Objective: A high rate of cerebral aneurysm recurrence following endovascular coiling has prompted the use of digital subtraction angiography (DSA) for interval follow-up. However, the utility of skull x-rays as an alternative screening method for aneurysm recurrence is unproperly characterized. Methods: Retrospective review of a prospective registry of ruptured and unruptured cerebral aneurysms. Anteroposterior and lateral skull x-rays were obtained immediately at the end of the procedure and at 6-month follow-up. Aneurysm recurrence was defined by comparing post-procedure and 6-month DSA imaging. A true positive was defined as a change in coil mass morphology on at least one projection with aneurysm recurrence on DSA, and a true negative defined as a stable coil mass on both projections and no recurrence on DSA. Receiver operating characteristic area under the curve (AUC) statistics was used to assess the performance of skull x-rays in identifying aneurysm recurrence. Results: A total of 118 cerebral aneurysms were evaluated with DSA imaging and skull x-rays. A change in coil mass morphology on one projection of skull x-rays correctly detected all true recurrences with a sensitivity of 100% (95% confidence interval [CI], 91-100%). Skull x-rays failed to identify a stable aneurysm coil mass in 15 cases, with a specificity of 79% (68-88%). Skull x-rays performed with AUC 0.8958 (95% CI, 0.8490-0.9431) in identifying aneurysm recurrence. Conclusions: The findings of our study suggest that skull x-rays may represent a lowcost, non-invasive screening tool to rule out aneurysm recurrence, which can potentially aid in decreasing the utilization of DSA in the follow-up of patients with coiled cerebral aneurysms.

9.
Eur Rev Med Pharmacol Sci ; 25(5): 2270-2280, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33755964

RESUMO

OBJECTIVE: Endovascular treatment (EVT) has been demonstrated superior to pharmacological thrombolysis in acute ischemic stroke (AIS) induced by extracranial internal carotid artery occlusion. This paper aims to summarize clinical evidence about EVT and assess its efficacy and safety on acute extracranial carotid occlusion. MATERIALS AND METHODS: We systematically reviewed all studies that reported endovascular therapy as carotid stenting, stent retriever, aspiration, and angioplasty for acute extracranial carotid occlusion. Literature retrieval was performed in PubMed, Embase, and Cochrane library, dated from January 1st, 2005 to December 31st, 2020. The primary endpoint was a favorable outcome rate. Major secondary endpoints were SICH incidence, 90-day mortality rate, and complications. Meta-analysis and subgroup analysis were conducted to identify predictors for prognosis. This systematic review has been registered in PROSPERO (CRD42020181154) on July 18, 2020. RESULTS: 10 studies with 620 patients were included in total. Endovascular approach presented a favorable outcome rate of 0.47 (0.37, 0.56), an acceptable 90-day mortality rate of 0.16 (0.13, 0.19), and a mild SICH rate of 0.07 (0.05, 0.10). Age and NIHSS at admission were negatively associated with favorable outcome, with odds ratio of 0.95 (0.92, 0.98) and 0.74 (0.62, 0.88) respectively. Lower age (p=0.049) and aspiration thrombectomy (p=0.041) predicted less SICH events. In subgroup in which time window > 6 hours, endovascular therapy presented similar encouraging results, with favorable outcome rate of 0.59 (0.51, 0.66), 90-day mortality rate of 0.11 (0.07, 0.17), and SICH rate of 0.04 (0.02, 0.09). CONCLUSIONS: EVT can effectively improve neurological function and reduce 90-day mortality for acute extracranial carotid occlusion patients without increasing the risk of symptomatic intracranial hemorrhage. Endovascular therapy is safe to perform from 6 to 24 hours after symptom onset.

10.
J Chem Theory Comput ; 17(3): 1678-1690, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33645221

RESUMO

A neural network (NN) approach was recently developed to construct accurate quasidiabatic Hamiltonians for two-state systems with conical intersections. Here, we derive the transformation properties of elements of 3 × 3 quasidiabatic Hamiltonians based on a valence bond (VB) model and extend the NN-based method to accurately diabatize the three lowest electronic singlet states of H3+, which exhibit the avoided crossing between the ground and first excited states and the conical intersection between the first and second excited states for equilateral triangle configurations (D3h). The current NN framework uses fundamental invariants (FIs) as the input vector and appropriate symmetry-adapted functions called covariant basis to account for the special symmetry of complete nuclear permutational inversion (CNPI). The resulting diabatic potential energy matrix (DPEM) can reproduce the ab initio adiabatic energies, energy gradients, and derivative couplings between adjacent states as well as the particular symmetry. The accuracy of DPEM is further validated by full-dimensional quantum dynamics calculations. The flexibility of the FI-NN approach based on the VB model shows great potential to resolve diabatization problems for many extended and multistate systems.

11.
J Mech Behav Biomed Mater ; 119: 104489, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33780850

RESUMO

The unique concept of phase reversion involving severe deformation of parent austenite into martensite, followed by annealing for a short duration, whereby the strain-induced martensite reverts to austenite, was adopted to obtain nano-grained/ultrafine-grained (NG/UFG) structure in a Cu-bearing biomedical austenitic stainless steel resulting in high strength-high ductility combination. Work hardening and accompanying deformation mechanism are two important aspects that govern the mechanical behavior of biomedical devices. Thus, post-mortem electron microscopy of the strained region was carried out to explore the differences in the deformation mechanisms induced by grain refinement, while the strain hardening behavior was analyzed by Crussard-Jaoul (C-J) analysis of the tensile stress-strain data. The strain hardening behavior consisted of four stages and was strongly affected by grain structure. Twinning-induced plasticity (TWIP) was the governing deformation mechanism in the NG/UFG structure and contributed to good ductility. In striking contrast, transformation-induced plasticity (TRIP) contributed to high ductility in the coarse-grained (CG) counterpart and was the governing strain hardening mechanism. When the grain size is less than ~1 µm, the increase in the strain energy and the austenite stability significantly reduce the possibility of strain-induced martensite transformation such that there is a distinct transition in deformation mechanism from nanoscale twinning in the NG/UFG structure to strain-induced martensite in CG structure. The differences in the deformation mechanisms are explained in terms of austenite stability - strain energy relationship.


Assuntos
Anti-Infecciosos , Aço Inoxidável , Cobre , Ligas Dentárias , Resistência à Tração
12.
J Chem Phys ; 154(7): 074301, 2021 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-33607900

RESUMO

A full-dimensional quantum dynamical study for the bimolecular reactions of hydrogen molecules with amino radicals for different isotopologues is reported. The nonreactive amino radical is described by two Radau vectors that are very close to the valence bond coordinates. Potential-optimized discrete variable representation basis is used for the vibrational coordinates of the amino radical. Starting from the reaction H2 + NH2, we study the isotope effects for the two reagents separately, i.e., H2 + NH2/ND2/NHD and H2/D2/HD + NH2. The effects of different vibrational mode excitations of the reagents on the reactivities are studied. Physical explanations about the isotope effects are also provided thoroughly including the influence of vibrational energy differences between the different isotopologues and the impact of the tunneling effect.

13.
Artigo em Chinês | MEDLINE | ID: mdl-33535335

RESUMO

Objective: To explore the self-conscious health status and related influencing factors of greenhouse agricultural workers in Beijing suburb, so as to provide scientific basis for developing strategies to improve and promote the occupational health conditions of those workers. Methods: According to the production characteristics and scale of the main agricultural districts or counties in the suburb of Beijing, 182 agricultural production personnel were randomly selected to investigate the general situation, occupational situation and self-conscious health status during June 2018 to December 2019. The relevant factors which may affect the self-conscious health conditions were also analyzed by statistical methods. Results: The detection or reported rate of self-conscious health problems was 51.6% (94/182) , among which 29.1% (53/182) workers reported musculoskeletal disorder diseases and 21.4% (39/182) workers reported nervous system diseases. And the self-conscious health status of greenhouse agricultural workers were statistically different in household registration, gender, marital status, working years, mixing or spraying pesticides, smoking or eating in the greenhouse (P<0.05) . Moreover, gender, mixing or spraying pesticide, eating and smoking behavior in the workplace all had an impact on the risk of self-conscious health status of greenhouse agricultural workers (P< 0.05) . Specifically, male is the protective factor to reduce the occurrence of self-conscious symptoms of greenhouse agricultural workers (OR=0.447, 95%CI: 0.234~0.852) , while mixing or spraying pesticides and smoking or eating behaviors in the workplace are the risk factors (OR=1.055, 2.524; 95%CI: 0.503~2.210, 1.107~5.755) . Conclusion: Reducing pesticide use from the source thus minimize related exposure opportunities, strengthening occupational health education thus foster good hygienic habits and improve individual protection consciousness are of great significance for the health protection of greenhouse agricultural workers in Beijing suburb.


Assuntos
Doenças dos Trabalhadores Agrícolas , Exposição Ocupacional , Praguicidas , Agricultura , Pequim , Fazendeiros , Nível de Saúde , Humanos , Masculino , Exposição Ocupacional/análise
14.
Cell Rep ; 34(5): 108721, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33535036

RESUMO

Spinal cord injury (SCI) is one of the most devastating neural injuries without effective therapeutic solutions. Astrocytes are the predominant component of the scar. Understanding the complex contributions of reactive astrocytes to SCI pathophysiologies is fundamentally important for developing therapeutic strategies. We have studied the molecular changes in the injury environment and the astrocyte-specific responses by astrocyte purification from injured spinal cords from acute to chronic stages. In addition to protein-coding genes, we have systematically analyzed the expression profiles of long non-coding RNAs (lncRNAs) (>200 bp), which are regulatory RNAs that play important roles in the CNS. We have identified a highly conserved lncRNA, Zeb2os, and demonstrated using functional assays that it plays an important role in reactive astrogliosis through the Zeb2os/Zeb2/Stat3 axis. These studies provide valuable insights into the molecular basis of reactive astrogliosis and fill the knowledge gap regarding the function(s) of lncRNAs in astrogliosis and SCI.

15.
J Phys Chem Lett ; : 2160-2165, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33626281

RESUMO

Ultracold chemical reactions involve collision temperatures approaching absolute zero, and for molecular systems that exhibit a barrierless and exoergic reaction path significant reactivity can occur. In addition, many molecules contain a conical intersection, and the associated geometric phase has been shown to significantly alter the outcome of ultracold reactions. Here we report a quantum dynamics study for the ultracold O + OH → H + O2 reaction. An analysis of the scattering wave functions reveals explicitly the nature of the quantum interference between the direct and looping reaction pathways around the conical intersection and thus illustrates how the reaction proceeds under the control of the geometric phase for the first time. The wave function analysis should generalize to other ultracold reactions that contain a conical intersection. Our findings indicate that quantum control techniques such as an optical lattice trap or the initial state orientation may be effective in controlling the reactivity.

16.
J Phys Chem Lett ; : 2259-2265, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33636082

RESUMO

Elucidating the dynamic couplings of hydrogen bonds remains an important and challenging goal for spectroscopic studies of bulk systems, because their vibrational signatures are masked by the collective effects of the fluctuation of many hydrogen bonds. Here we utilize size-selected infrared spectroscopy based on a tunable vacuum ultraviolet free electron laser to unmask the vibrational signatures for the dynamic couplings in neutral trimethylamine-water and trimethylamine-methanol complexes, as microscopic models with only one single hydrogen bond holding two molecules. Surprisingly broad progression of OH stretching peaks with distinct intensity modulation over ∼700 cm-1 is observed for trimethylamine-water, while the dramatic reduction of this progression in the trimethylamine-methanol spectrum offers direct experimental evidence for the dynamic couplings. State-of-the-art quantum mechanical calculations reveal that such dynamic couplings are originated from strong Fermi resonance between the stretches of hydrogen-bonded OH and several motions of the solvent water/methanol, such as translation, rocking, and bending, which are significant in various solvated complexes commonly found in atmospheric and biological systems.

17.
Stroke ; 52(3): 1022-1029, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33535778

RESUMO

BACKGROUND AND PURPOSE: The optimal endovascular stroke therapy (EVT) care delivery structure is unknown. Here, we present our experience in creating an integrated stroke system (ISS) to expand EVT availability throughout our region while maintaining hospital and physician quality standards. METHODS: We identified all consecutive patients with large vessel occlusion acute ischemic stroke treated with EVT from January 2014 to February 2019 in our health care system. In October 2017, we implemented the ISS, in which 3 additional hospitals (4 total) became EVT-performing hospitals (EPHs) and physicians were rotated between all centers. The cohort was divided by time into pre-ISS and post-ISS, and the primary outcome was time from stroke onset to EPH arrival. Secondary outcomes included hospital and procedural quality metrics. We performed an external validation using data from the Southeast Texas Regional Advisory Council. RESULTS: Among 513 patients with large vessel occlusion acute ischemic stroke treated with EVT, 58% were treated pre-ISS and 43% post-ISS. Over the study period, EVT procedural volume increased overall but remained relatively low at the 3 new EPHs (<70 EVT/y). After ISS, the proportion of patients who underwent interhospital transfer decreased (46% versus 37%; P<0.05). In adjusted quantile regression, ISS implementation resulted in a reduction of time from stroke onset to EPH arrival by 40 minutes (P<0.01) and onset to groin puncture by 29 minutes (P<0.05). Rates of postprocedural hemorrhage, modified Thrombolysis in Cerebral Infarction (TICI) 2b/3, and 90-day modified Rankin Scale were comparable at the higher and lower volume EPHs. The improvement in onset-to-arrival time was not reflective of overall improvement in secular trends in regional prehospital care. CONCLUSIONS: In our system, increasing EVT availability decreased time from stroke onset to EPH arrival. The ISS provides a framework to maintain quality in lower volume hospitals.

18.
Science ; 371(6532): 936-940, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33632844

RESUMO

The effect of electron spin-orbit interactions on chemical reaction dynamics has been a topic of much research interest. Here we report a combined experimental and theoretical study on the effect of electron spin and orbital angular momentum in the F + HD → HF + D reaction. Using a high-resolution imaging technique, we observed a peculiar horseshoe-shaped pattern in the product rotational-state-resolved differential cross sections around the forward-scattering direction. The unusual dynamics pattern could only be explained properly by highly accurate quantum dynamics theory when full spin-orbit characteristics were considered. Theoretical analysis revealed that the horseshoe pattern was largely the result of quantum interference between spin-orbit split-partial-wave resonances with positive and negative parities, providing a distinctive example of how spin-orbit interaction can effectively influence reaction dynamics.

19.
Arch Pharm (Weinheim) ; 354(6): e2000360, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33555065

RESUMO

Sugar nucleotidyltransferases (SNTs) participate in various biosynthesis pathways constructing polysaccharides in Gram-negative bacteria. In this study, a triple-targeting inhibitory activity of Rose Bengal against SNTs such as d-glycero-α-d-manno-heptose-1-phosphate guanylyltransferase (HddC), d-glycero-ß-d-manno-heptose-1-phosphate adenylyltransferase (HldC), and 3-deoxy-d-manno-oct-2-ulosonic acid cytidylyltransferase (KdsB) from Burkholderia pseudomallei is provided. Rose Bengal effectively suppresses the nucleotidyltransferase activity of the three SNTs, and its IC50 values are 10.42, 0.76, and 5.31 µM, respectively. Interestingly, Rose Bengal inhibits the three enzymes regardless of their primary, secondary, tertiary, and quaternary structural differences. The experimental results indicate that Rose Bengal possesses the plasticity to shape its conformation suitable to interact with the three SNTs. As HddC functions in the formation of capsular polysaccharides and HldC and KdsB produce building blocks to constitute the inner core of lipopolysaccharide, Rose Bengal is a potential candidate to design antibiotics in a new category. In particular, it can be developed as a specific antimelioidosis agent. As the mortality rate of the infected people caused by B. pseudomallei is quite high, there is an urgent need for specific antimelioidosis agents. Therefore, a further study is being carried out with derivatives of Rose Bengal.

20.
J Neurooncol ; 152(1): 153-162, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33492602

RESUMO

INTRODUCTION: Despite aggressive treatment, glioblastoma invariably recurs. The optimal treatment for recurrent glioblastoma (rGBM) is not well defined. Stereotactic radiosurgery (SRS) for rGBM has demonstrated favorable outcomes for selected patients; however, its efficacy in molecular GBM subtypes is unknown. We sought to identify genetic alterations that predict response/outcomes from SRS in rGBM-IDH-wild-type (IDH-WT). METHODS: rGBM-IDH-WT patients undergoing SRS at first recurrence and tested by next-generation sequencing (NGS) were reviewed (2009-2018). Demographic, clinical, and molecular characteristics were evaluated. NGS interrogating 205-genes was performed. Primary outcome was survival from GK-SRS assessed by Kaplan-Meier method and multivariable Cox proportional-hazards. RESULTS: Sixty-three lesions (43-patients) were treated at 1st recurrence. Median age was 61-years. All patients were treated with resection and chemoradiotherapy. Median time from diagnosis to 1st recurrence was 8.7-months. Median cumulative volume was 2.895 cm3 and SRS median marginal dose was 18 Gy (median isodose-54%). Bevacizumab was administered in 81.4% patients. PFS from SRS was 12.9-months. Survival from SRS was 18.2-months. PTEN-mutant patients had a longer PFS (p = 0.049) and survival from SRS (p = 0.013) in multivariable analysis. Although no statistically significant PTEN-mutants patients had higher frequency of radiation necrosis (21.4% vs. 3.4%) and lower in-field recurrence (28.6% vs. 37.9%) compared to PTEN-WT patients. CONCLUSIONS: SRS is a safe and effective treatment option for selected rGBM-IDH-WT patients following first recurrence. rGBM-IDH-WT harboring PTEN-mutation have improved survival with salvage SRS compared to PTEN-WT patients. PTEN may be used as a molecular biomarker to identify a subset of rGBM patients who may benefit the most from SRS.

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