RESUMO
The field of biomimetic synthesis seeks to apply biosynthetic hypotheses to the efficient construction of complex natural products. This approach can also guide the revision of incorrectly assigned structures. Herein, we describe the evolution of a concise total synthesis and structural reassignment of hyperelodione D, a tetracyclic meroterpenoid derived from a Hypericum plant, alongside some biogenetically related natural products, erectones A and B. The key step in the synthesis of hyperelodione D forms six stereocentres and three rings in a bioinspired cascade reaction that features an intermolecular Diels-Alder reaction, an intramolecular Prins reaction and a terminating cycloetherification.
Assuntos
Produtos Biológicos , Hypericum , Produtos Biológicos/química , Biomimética , Reação de CicloadiçãoRESUMO
2,5-Bis(tert-butyldimethylsilyloxy)furans are established as vicinal bisketene equivalents for application as dienes in the Diels-Alder reaction. Cycloaddition with olefinic dienophiles, under exceptionally mild conditions, enables convergent access to highly substituted para-hydroquinones in unprotected form via a one-pot Diels-Alder/ring-opening/tautomerization sequence. The synthesis of para-benzoquinones from acetylenic dienophiles, including benzynes, is also demonstrated, and 2,5-bis(tert-butyldimethylsilyloxy)pyrroles are established as competent dienes for the synthesis of para-iminoquinones. Application in natural product synthesis enables gram-scale access to the neuroprotective agent (±)-indanostatin.
RESUMO
The total synthesis of nyingchinoidsâ A and B has been achieved through successive rearrangements of a 1,2-dioxane intermediate that was assembled using a visible-light photoredox-catalysed aerobic [2+2+2] cycloaddition. Nyingchinoidâ D was synthesised with a competing [2+2] cycloaddition. Based on NMR data and biosynthetic speculation, we proposed a structure revision of the related natural product rasumatraninâ D, which was confirmed through total synthesis. Under photoredox conditions, we observed the conversion of a cyclobutane into a 1,2-dioxane through retro-[2+2] cycloaddition followed by aerobic [2+2+2] cycloaddition.
Assuntos
Materiais Biomiméticos/síntese química , Luz , Terpenos/síntese química , Materiais Biomiméticos/química , Catálise , Estrutura Molecular , Oxirredução , Processos Fotoquímicos , Estereoisomerismo , Terpenos/químicaRESUMO
As stewards of public and environmental health, mosquito control agencies are rightfully concerned about impacts on nontarget organisms. This study examined the impact of a modern, pyrethroid based ground adulticide program using ultra-low volume applications in a metropolitan county in central Florida. Nontarget insects and mosquitoes were collected in a before-after control-impact design at 21 sites over 1.5 years. While mosquitoes were reduced, we found no evidence for reduction of nontarget insects, regardless of taxon. Night-flying Lepidoptera may experience greater risk than other nontarget taxa, but overall effects of adulticide missions on this group were low and inconsistent. Instead, meteorology, habitat, and phenology dominate patterns of nontarget abundance. Mosquito reduction was more clearly observed and corrected post-mission reduction was consistent with results expected in complex urban and suburban treatment zones.
Assuntos
Culicidae , Insetos , Inseticidas , Controle de Mosquitos , Piretrinas , Animais , FloridaRESUMO
Mosquito larval control by biorational larvicides plays a crucial role in mosquito and mosquito-borne disease management. However, the availability of larvicides that meet the criteria of efficacy, safety, and quality is limited and conventional pesticides are no longer preferred for larval control. Although efforts are made to research new active ingredients (AIs), it is equally important to innovate new formulations based on currently available AIs such as microbial agents and insect growth regulators. Studies were therefore conducted to compare the laboratory activity and semi-field efficacy of OmniPrene® G and Altosid® Pellets with DR-tech, both containing 4.25% S-methoprene, at 2.8 kg/ha and 11.2 kg/ha against the yellow fever mosquito Aedes aegypti (L.) in outdoor microcosms. Both products performed equally in bioassays against the test species with comparable inhibition of emergence activities. In the semi-field study, the lower dose of Altosid Pellets at 2.8 kg/ha, showed lower efficacy than OmniPrene G during the initial 6 weeks; this difference became negligible on week 7, followed by higher efficacy in Altosid Pellets on weeks 8 and 9. More uniform efficacy was observed at the higher dose of 11.2 kg/ha. Equal performance was revealed during weeks 2 to 6, with the OmniPrene G outperforming the Altosid Pellets in week 1, but the opposite during weeks 7 to 9. Mortality patterns were similar in both products, i.e., majority of mortality occurred before emergence, although more incomplete emergence was noted in lower doses, particularly in Altosid Pellets. Overall, newly available OmniPrene G provided comparable activity and efficacy with Altosid Pellets against the test species, with the advantages of fast initial AI release and even coverage, particularly when applied at low doses.
RESUMO
Combined effects of disturbance and productivity on ecological diversity have been considered for decades as the dynamic equilibrium model (DEM) but are rarely tested together. Instead, most studies focus on either the intermediate disturbance hypothesis or sometimes the intermediate productivity hypothesis. In addition, most analyses of disturbance and productivity effects have relied on nonexperimental patterns, limited sample sizes, inaccurate proxies for productivity, and/or simple measures of diversity. The DEM operates at regional and local scales; here, we conducted a year-long experiment at local scales using submersed aquatic vegetation in outdoor mesocosms with a factorial combination of physical disturbance and productivity treatments. We evaluated diversity in several ways, directly measured productivity, and compared alternative hypotheses using model selection. The DEM was supported for effective diversity; both productivity and disturbance effects were clear, though productivity effects were stronger. Other diversity measures for the simple communities in the mesocosms did not clearly reflect treatments. The DEM is a valuable general framework for understanding disturbance and productivity effects on ecological systems and is made more general by minor conceptual adjustments here.
RESUMO
BACKGROUND: We planned an observational study to assess obstetric anesthesia services nationwide. We aimed to assess the effect of the anesthesia workload/workforce ratio on quality and safety outcomes of obstetric anesthesia care. METHODS: Observers prospectively collected data from labor units over 72 h (Wednesday, Thursday and Friday). Independent variables were workload (WL) and workforce (WF). WL was assessed by the Obstetric Anesthesia Activity Index (OAAI), which is the estimated time in a 24-h period spent on epidurals and all cesarean deliveries. Workforce (WF) was assessed by the number of anesthesiologists dedicated to the labor ward per week. Dependent variables were the time until anesthesiologist arrival for epidural (quality measure) and the occurrence of general anesthesia for urgent Cesarean section, CS, (safety measure). This census included vaginal deliveries and unscheduled (but not elective) CS. RESULTS: Data on 575 deliveries are from 12 maternity units only, primarily because a major hospital chain chose not to participate; eight other hospitals lacked institutional review board approval. The epidural response rate was 94.4%; 321 of 340 parturients who requested epidural analgesia (EA) received it. Of the 19 women who requested EA but gave birth without it, 14 (77%) were due to late arrival of the anesthesiologist. Median waiting times for anesthesiologist arrival ranged from 5 to 28 min. The OAAI varied from 4.6 to 25.1 and WF ranged from 0 to 2 per shift. Request rates for EA in hospitals serving predominantly orthodox Jewish communities and in peripheral hospitals were similar to those of the entire sample. More than a fifth (13/62; 21%) of the unscheduled CS received general anesthesia, and of these almost a quarter (3/13; 23%) were attributed to delayed anesthesiologist arrival. CONCLUSIONS: Inadequate WF allocations may impair quality and safety outcomes in obstetric anesthesia services. OAAI is a better predictor of WL than delivery numbers alone, especially concerning WF shortage. To assess the quality and safety of anesthetic services to labor units nationally, observational data on workforce, workload, and clinical outcomes should be collected prospectively in all labor units in Israel.
Assuntos
Analgesia Epidural , Anestesia Obstétrica , Cesárea , Feminino , Humanos , Israel , Gravidez , Recursos HumanosRESUMO
The clinical experience in recent years regarding vocational outcome of patients following traumatic brain injury (TBI) led to the impression of worse outcomes in recent years. A comparative study was therefore conducted between a "control group" of patients who were treated during the years 1980-1985 (n=147), evaluated during 1993 and a "research group" hospitalized between 1998-2001 and evaluated during 2004 (n=247). No significant differences were found between the control and research groups regarding most of the demographic and injury-related parameters. Significant differences were found regarding the length of inpatient rehabilitation stay which was found to be shorter in the "research group" (165 and 117 days respectively, p < 0.0001). More patients in the research group were left with cognitive and behavioral disturbances at the time of discharge (p < 0.0001) and less patients in the research group were able to achieve gainful employment (50.6% and 34.8% respectively, p < 0.0001). On many occasions, recommendations given at the time of discharge were not fulfilled. The compliance for further treatment was quite high regarding physiotherapy (85%) but when it came to cognitive or behavioral treatment the percentage dropped to only about 60%. Patients were not satisfied with the attitudes of their health care providers, especially with regard to health funds and insurance companies. It is concluded that discharge of patients who may physically look fit is premature. The effect of residual cognitive and behavioral disturbances, which, at the end, determine the overall outcome of patients with TBI, is underestimated and treatment is prematurely discontinued, leading to a less successful outcome for these young patients in recent years. It is speculated that any saving in cost due to shortening of the stay in hospital leads to a worse outcome and possible larger compensations due to inability to achieve gainful employment.
Assuntos
Lesões Encefálicas/reabilitação , Distribuição de Qui-Quadrado , Humanos , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: The outcomes of spinal cord injuries (SCI) have improved over the last decades. OBJECTIVES: Update on outcomes following SCI in Israel. METHODS: Data on 259 SCI patients admitted for rehabilitation between 1992 and 2003 were collected. Survival rates were estimated using the product limit (Kaplan-Meyer) method and their association with risk factors was analyzed with the Cox Proportional Hazard model. Neurological recovery was determined by the change in Frankel grades during rehabilitation, and compared with data from a previous study using the chi2 test. Effects on neurological recovery were examined using logistic regression. Effects on length of stay (LOS) were assessed by ANOVA. RESULTS: The number of SCI patients approximately doubled during the 1990s. Survival rate was 88% and 86.3%, 5 and 10 years respectively after injury. Survival was negatively associated with age (p < 0.001) and with high spinal level of injury (p < 0.001). Thirty eight percent of patients with Frankel grades A, B, or C (SCI that do not allow functioning) recovered to grades D or E (that allow functioning). Average LOS was 135 days. LOS was positively associated with Frankel grade and negatively with recent SCI onset. CONCLUSIONS: The demand for rehabilitation after SCI increased significantly in the studied decade. In Israel, survival and neurological recovery rates after SCI rehabilitation are close to those reported in other countries. Despite the decrease in LOS, in recent years, survival is at least as long as before, and neurological recovery has improved significantly.
Assuntos
Traumatismos da Medula Espinal/reabilitação , Humanos , Israel , Tempo de Internação , Estudos Retrospectivos , Traumatismos da Medula Espinal/mortalidade , Taxa de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
Eighteen community-dwelling first-stroke survivors, aged 45 to 65, underwent following examinations: Romberg's Test, standing on the unaffected leg, Emory Fractional Ambulation Profile, the Berg Balance Test, the Timed 'Up and Go' Test and the Duke Health Profile. They were then randomly divided into two matched groups of 9 subjects each. The study group (SG) received Tai Chi exercises and the control group (CG) physiotherapy exercises focused on improvement of balance, both groups for 1 h twice weekly for 12 weeks. On completion of exercises, SG subjects showed improvement in social and general functioning whereas CG subjects showed improvement in balance and speed of walking. It is concluded that there are potential and no adverse effects in Tai Chi practice in stroke survivors.
Assuntos
Reabilitação do Acidente Vascular Cerebral , Tai Chi Chuan , Idoso , Terapia por Exercício , Feminino , Humanos , Pessoa de Meia-Idade , Equilíbrio Postural , Acidente Vascular Cerebral/fisiopatologia , Resultado do Tratamento , CaminhadaRESUMO
BACKGROUND: Women with deleterious mutations in BRCA genes are at increased risk of breast cancer. However, the penetrance of the genetic trait may be regulated through environmental factors. This multinational case-only study tested the interaction between oral contraceptive use and genetic susceptibility in the occurrence of breast cancer. METHODS: We recruited 3,123 patients diagnosed with breast cancer before the age of 45 years. Participants were classified according to their probability of carrying a BRCA mutation on the basis of their family history of breast and ovarian cancer. According to a case-only approach, the frequency of relevant exposures among breast cancer cases with high probability of BRCA mutation ("genetic cases") was compared with the frequency of the same exposures among breast cancer cases with a low probability of BRCA mutation ("sporadic cases"). The interaction odds ratios (OR) and 95% confidence intervals (CI) for oral contraceptive use were estimated by unconditional logistic regression, after controlling for potentially confounding variables. RESULTS: The analysis was carried out comparing 382 "genetic" and 1,333 "sporadic" cases. We found a borderline significant interaction between genetic breast cancer and oral contraceptive use for ever users compared with never users (OR, 1.3; 95% CI, 1.0-1.7). The greatest interaction OR was found for women who started using pill at 18 to 20 years (OR, 1.6; 95% CI, 1.1-2.3). CONCLUSION: These results suggest that BRCA mutation carriers, as well as women with a significant family history of breast and ovarian cancer are more vulnerable to exogenous hormones in oral contraceptives.
Assuntos
Proteína BRCA2/genética , Neoplasias da Mama , Anticoncepcionais Orais/efeitos adversos , Genes BRCA1 , Predisposição Genética para Doença , Penetrância , Adolescente , Adulto , Idade de Início , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Estudos de Casos e Controles , Europa (Continente)/epidemiologia , Feminino , Humanos , Modelos Logísticos , Modelos Genéticos , Linhagem , Medição de Risco , Fatores de Risco , Inquéritos e Questionários , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: Frequent attenders in primary care are a professional challenge for family physicians, and the medical costs of their care can be very high. Some of them suffer from somatization and are concerned solely with their physical complaints, although somatic complaints are the most common presentation of anxiety and depression. To assess and treat these patients comprehensively, a multidisciplinary clinic was created in the community. METHODS: This study describes the first 40 patients referred to the clinic. All patients completed a mental health screening questionnaire and a functional assessment of health. The utilization of medical resources was assessed by chart review for the year before and the year after the first encounter in the clinic. The intervention consisted of a comprehensive bio-psychosocial consultation where life history and medical symptoms were woven together into a new narrative. The intervention also included pharmacological treatment and short-term psychological interventions. RESULTS: The majority of referred patients were women and their average age was 52 years. Headache was the leading symptom, followed by fatigue. The mean number of reported symptoms for each individual patient was 10. Mental health problems were mainly somatization, depression and anxiety. The average yearly costs per person of US$4035 were reduced to US$1161 the year following referral. CONCLUSIONS: The integrated approach of the clinic satisfied at least three needs: of the patient, of the referring physician and of the health maintenance organization. The results of this uncontrolled pilot study suggest that this intervention helped to modify illness behaviour, decreasing the costs of medical investigations.