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1.
Proc Natl Acad Sci U S A ; 117(46): 28754-28762, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33148804

RESUMO

The mechanosensitive channel of small conductance (MscS) is the prototype of an evolutionarily diversified large family that fine-tunes osmoregulation but is likely to fulfill additional functions. Escherichia coli has six osmoprotective paralogs with different numbers of transmembrane helices. These helices are important for gating and sensing in MscS but the role of the additional helices in the paralogs is not understood. The medium-sized channel YnaI was extracted and delivered in native nanodiscs in closed-like and open-like conformations using the copolymer diisobutylene/maleic acid (DIBMA) for structural studies. Here we show by electron cryomicroscopy that YnaI has an extended sensor paddle that during gating relocates relative to the pore concomitant with bending of a GGxGG motif in the pore helices. YnaI is the only one of the six paralogs that has this GGxGG motif allowing the sensor paddle to move outward. Access to the pore is through a vestibule on the cytosolic side that is fenestrated by side portals. In YnaI, these portals are obstructed by aromatic side chains but are still fully hydrated and thus support conductance. For comparison with large-sized channels, we determined the structure of YbiO, which showed larger portals and a wider pore with no GGxGG motif. Further in silico comparison of MscS, YnaI, and YbiO highlighted differences in the hydrophobicity and wettability of their pores and vestibule interiors. Thus, MscS-like channels of different sizes have a common core architecture but show different gating mechanisms and fine-tuned conductive properties.

2.
BMC Med Educ ; 20(1): 447, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33213439

RESUMO

BACKGROUND: In undergraduate medical education, patient safety concepts and understanding of medical errors are under-represented. This problem is more evident in low-income settings. The aim of this study was to explore undergraduate medical students' attitudes towards patient safety in the low-income setting of the Gaza Strip. METHODS: A cross-sectional, descriptive study included medical students of the two medical schools in the Gaza Strip with 338 medical students completing the Attitudes to Patient Safety Questionnaire-IV (APSQ-IV), which examines patient attitudes in 29 items over 10 domains. Results are represented as means ± standard deviations for each item and domain as well as percentage of positive responses to specific items. RESULTS: Medical students reported slightly positive patient safety attitudes (4.7 ± 0.5 of 7) with the most positive attitudes in the domains of situational awareness, importance of patient safety in the curriculum, error inevitability and team functioning. While no negative attitudes were reported, neutral attitudes were found in the domains of professional incompetence as a cause of error and error reporting confidence. Study year and gender had no significant association with patient safety attitudes, except for disclosure responsibility, where male students displayed significantly more positive attitudes. The study university was significantly associated with three of the 10 examined domains, all of which involved understanding of medical errors, for which students of University 2 (who had undergone limited patient safety training) held significantly more positive attitudes, compared with students of University 1 (who did not have structured patient safety training). CONCLUSION: Medical students' patient safety attitudes were very similar among students from both universities, except for understanding of medical error, for which students, who had received structured training in this topic, displayed significantly more positive attitudes. This underlines the power of the 'hidden curriculum', where students adjust to prevalent cultures in local hospitals, while they do their clinical training. Furthermore, it highlights the need for a systematic inclusion of patient safety content in local undergraduate curricula.

3.
Mol Pharm ; 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33118829

RESUMO

Controlling physicochemical properties of light-unresponsive drugs, by light, prima facie, a paradox approach. We expanded light control by ion pairing light-unresponsive salicylate or ibuprofen to photoswitchable azobenzene counterions, thereby reversibly controlling supramolecular structures, hence the drugs' physicochemical and kinetic properties. The resulting ion pairs photoliquefied into room-temperature ionic liquids under ultraviolet light. Aqueous solutions showed trans-cis-dependent supramolecular structures under a light with wormlike aggregates decomposing into small micelles and vice versa. Light control allowed for permeation through membranes of cis-ibuprofen ion pairs within 12 h in contrast to the trans ion pairs requiring 72 h. In conclusion, azobenzene ion-pairing expands light control of physicochemical and kinetic properties to otherwise light-unresponsive drugs.

4.
Elife ; 92020 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-32795390

RESUMO

Hepatitis B virus (HBV) is an important but difficult to study human pathogen. Most basics of the hepadnaviral life-cycle were unraveled using duck HBV (DHBV) as a model although DHBV has a capsid protein (CP) comprising ~260 rather than ~180 amino acids. Here we present high-resolution structures of several DHBV capsid-like particles (CLPs) determined by electron cryo-microscopy. As for HBV, DHBV CLPs consist of a dimeric α-helical frame-work with protruding spikes at the dimer interface. A fundamental new feature is a ~ 45 amino acid proline-rich extension in each monomer replacing the tip of the spikes in HBV CP. In vitro, folding of the extension takes months, implying a catalyzed process in vivo. DHBc variants lacking a folding-proficient extension produced regular CLPs in bacteria but failed to form stable nucleocapsids in hepatoma cells. We propose that the extension domain acts as a conformational switch with differential response options during viral infection.

5.
Eur J Cardiovasc Nurs ; : 1474515120938235, 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32631080

RESUMO

BACKGROUND: Hypertension is one of the most prevalent long-term diseases seen in many countries, including Palestine. Patients with poorly controlled blood pressure are more likely to develop several complications. Therefore; it is imperative to control their blood pressure by improving their adherence to the treatment regimen. AIM: The objective of this study was to evaluate the impact of using a mobile phone app on the level of adherence to treatment regimens among hypertensive patients in the Gaza Strip. METHODS AND RESULTS: This study used an experimental design with a pre and post-intervention assessment. Using the Hill-Bone compliance to high blood pressure therapy scale, 191 participants completed the study: 94 in the control group and 97 in the intervention group. The intervention group used a phone app which reminds participants to take their medication, reminding them about their follow-up appointments and sending educational information about hypertension management. After 3 months of intervention, the level of adherence to treatment was reassessed. Results showed that participants in both groups showed a significant improvement in adherence levels, with higher improvements in the intervention group in the total score as well as all three domain scores: adherence to medication, diet and keeping appointments. CONCLUSION: The use of a mobile phone app resulted in improvements in adherence to hypertension treatment. Thus, this study confirms the potential effectiveness of mobile technology in improving treatment adherence in hypertension and an opportunity to reduce cardiovascular mortality and morbidity. However, wider adoption has to be accompanied by ongoing evaluation and integration in public health systems.

6.
ACS Appl Mater Interfaces ; 12(22): 24531-24543, 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32378873

RESUMO

Polymeric micelles are typically characterized as core-shell structures. The hydrophobic core is considered as a depot for hydrophobic molecules, and the corona-forming block acts as a stabilizing and solubilizing interface between the core and aqueous milieu. Tremendous efforts have been made to tune the hydrophobic block to increase the drug loading and stability of micelles, whereas the role of hydrophilic blocks is rarely investigated in this context, with poly(ethylene glycol) (PEG) being the gold standard of hydrophilic polymers. To better understand the role of the hydrophilic corona, a small library of structurally similar A-B-A-type amphiphiles based on poly(2-oxazoline)s and poly(2-oxazine)s is investigated by varying the hydrophilic block A utilizing poly(2-methyl-2-oxazoline) (pMeOx; A) or poly(2-ethyl-2-oxazoline) (pEtOx; A*). In terms of hydrophilicity, both polymers closely resemble PEG. The more hydrophobic block B bears either a poly(2-oxazoline) and poly(2-oxazine) backbone with C3 (propyl) and C4 (butyl) side chains. Surprisingly, major differences in loading capacities from A-B-A > A*-B-A > A*-B-A* is observed for the formulation with two poorly water-soluble compounds, curcumin and paclitaxel, highlighting the importance of the hydrophilic corona of polymer micelles used for drug formulation. The formulations are also characterized by various nuclear magnetic resonance spectroscopy methods, dynamic light scattering, cryogenic transmission electron microscopy, and (micro) differential scanning calorimetry. Our findings suggest that the interaction between the hydrophilic block and the guest molecule should be considered an important, but previously largely ignored, factor for the rational design of polymeric micelles.

7.
BMC Health Serv Res ; 20(1): 388, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32380987

RESUMO

BACKGROUND: Patient safety is important, as in increasingly complex medical systems, the potential for unintended harm to patients also increases. This study assessed the attitudes of doctors in the Gaza Strip towards patient safety and medical error. It also explored variables that impacted their attitudes. METHODS: Doctors, working for at least 6 months in one of the four major government hospitals of the Gaza Strip, were invited to complete a 28-item, self-administered Arabic version of the Attitudes to Patient Safety Questionnaire III (APSQ-III); which assessed patient safety attitudes over nine domains, independent of the workplace. RESULTS: A total of 150 doctors from four government hospitals participated in this study, representing 43.5% of all 345 doctors working in the four study hospitals at the time of the study. The mean age was 36.6 (±9.7) years. The majority (72.7%) were males, 28.7% worked in surgical, 26.7% in pediatric, 23.3% in medical, 16.7% in obstetrics and gynecology, and 4.7% in other departments. Most participants (62.0%) had never received patient safety training. The overall APSQ score was 3.58 ± 0.3 (of a maximum of 5). The highest score was received by the domain "Working hours as a cause of errors" (4.16) and the lowest score by "Importance of Patient Safety in the Curriculum" (3.25). Older doctors with more professional experience had significantly higher scores than younger doctors (p = 0.003), demonstrating more positive attitudes toward patient safety. Furthermore, patient safety attitudes became more positive with increasing years of experience in some domains. However, no significant impact on overall APSQ scores was found by workplace, specialty or whether the participants had received previous training about patient safety. CONCLUSION: Doctors in Gaza demonstrated relatively positive patient safety attitudes in areas of "team functioning" and "working hours as a cause for error", but neutral attitudes in understanding medical error or patient safety training within the curriculum. Patient safety concepts appear to be acquired by doctors via informal learning over time in the job. Inclusion of such concepts into formal postgraduate curricula might improve patient safety attitudes among younger and less experienced doctors, support behaviour change and improve patient outcomes.


Assuntos
Atitude do Pessoal de Saúde , Corpo Clínico Hospitalar/psicologia , Segurança do Paciente , Adulto , Estudos Transversais , Feminino , Hospitais Públicos , Humanos , Masculino , Corpo Clínico Hospitalar/estatística & dados numéricos , Pessoa de Meia-Idade , Oriente Médio , Inquéritos e Questionários
8.
BMC Public Health ; 20(1): 414, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32228661

RESUMO

BACKGROUND: In low-income settings, cancer is often diagnosed in advanced stages due to late presentation. Good public awareness of cancer signs and symptoms has a positive impact on the time patients take before they present to healthcare professionals. Therefore, this study examined public knowledge of cancer signs and symptoms as well as risk factors in Gaza. METHODS: This was a cross-sectional study. Participants were recruited from adult visitors (≥18 years) to governmental hospitals covering all five governorates of Gaza, and adolescent students (15 to 17 years) from 10 high schools in corresponding locations. An Arabic version of the Cancer Awareness Measure (CAM) was completed in a face-to-face interview. It described demographic data and knowledge of: cancer prevalence, age-related risk, signs and symptoms as well as risk factors both in recall and recognition questions. RESULTS: Of 3033 participants invited, 2886 completed the CAM (response rate = 95.2%). Adult mean age ± standard deviation was 33.7 ± 11.7 years and that of adolescents was 16.3 ± 0.8 years. Half of the participants (n = 1457, 50.5%) were adolescent (781 females; 53.6%) and 1429 (49.5%) were adult (702 females; 49.1%). About two thirds (n = 1885) thought about cancer as unrelated to age. Only 196 participants (6.8%) identified colorectal cancer as the most common cancer among men. Awareness of cancer signs/symptoms was poor to fair, where 'lump' was most commonly recognized (n = 2227, 77.2%) and 'change of bowel habit' the least (n = 670, 23.2%). Only 217 participants (7.5%) had a good level of recognizing risk factors with 'smoking' being the most identified and 'eating less than five portions of fruits and vegetables a day' the least. There was a higher likelihood for adults to identify most cancer signs/symptoms and risk factors than adolescents, except for recalling 'unexplained pain', 'persistent cough/hoarseness', 'non-healing ulcer', 'smoking', and 'eating less than five portions of fruits and vegetables a day'. CONCLUSION: Public awareness of cancer signs/symptoms and risk factors needs to improve to facilitate early presentation and diagnosis in Gaza. Combining the delivery of public campaigns with tailored education to population groups, including the youth, may increase their knowledge and maintain its impact.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Neoplasias/psicologia , Adolescente , Adulto , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/psicologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oriente Médio/epidemiologia , Neoplasias/epidemiologia , Neoplasias/etiologia , Prevalência , Fatores de Risco , Estudantes/psicologia , Adulto Jovem
9.
ACS Appl Mater Interfaces ; 12(11): 12445-12456, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32142257

RESUMO

Amphiphilic block copolymers that undergo (reversible) physical gelation in aqueous media are of great interest in different areas including drug delivery, tissue engineering, regenerative medicine, and biofabrication. We investigated a small library of ABA-type triblock copolymers comprising poly(2-methyl-2-oxazoline) as the hydrophilic shell A and different aromatic poly(2-oxazoline)s and poly(2-oxazine)s cores B in an aqueous solution at different concentrations and temperatures. Interestingly, aqueous solutions of poly(2-methyl-2-oxazoline)-block-poly(2-phenyl-2-oxazine)-block-poly(2-methyl-2-oxazoline) (PMeOx-b-PPheOzi-b-PMeOx) undergo inverse thermogelation below a critical temperature by forming a reversible nanoscale wormlike network. The viscoelastic properties of the resulting gel can be conveniently tailored by the concentration and the polymer composition. Storage moduli of up to 110 kPa could be obtained while the material retains shear-thinning and rapid self-healing properties. We demonstrate three-dimensional (3D) printing of excellently defined and shape-persistent 24-layered scaffolds at different aqueous concentrations to highlight its application potential, e.g., in the research area of biofabrication. A macroporous microstructure, which is stable throughout the printing process, could be confirmed via cryo-scanning electron microscopy (SEM) analysis. The absence of cytotoxicity even at very high concentrations opens a wide range of different applications for this first-in-class material in the field of biomaterials.

10.
BMC Surg ; 20(1): 21, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32000748

RESUMO

BACKGROUND: Surgical site infection (SSI) is one of the most common hospital-acquired infections and is associated with serious impact on the rates of morbidity, mortality as well as healthcare costs. This study examined factors influencing the application of several intraoperative preventive measures of SSI by surgeons and surgical residents in the Gaza Strip. METHODS: A cross-sectional study was conducted from December 2016 to February 2017 at the operation rooms of the three major hospitals located in the Gaza-Strip, Palestine. Inclusion criteria for patients were being adult (aged ≥18 years), no history of wound infection at time of operation and surgical procedure under general anaesthesia with endotracheal intubation. The association between different patient- and procedure-related SSI risk factors and adherence to several intraoperative SSI preventive measures was tested. RESULTS: In total, 281 operations were observed. The mean patient age ± standard deviation (SD) was 38.4 ± 14.6 years and the mean duration of surgery ± SD was 58.2 ± 32.1 minutes. A hundred-thirty-two patients (47.0%) were male. Location and time of the operation were found to have significant associations with adherence to all SSI preventive measures except for antibiotic prophylaxis. Type of operation had a significant association with performing all measures except changing surgical instruments. Patient age did not have a statistically significant association with adherence to any measure. CONCLUSION: The results suggest that the surgeon could be a major factor that can lead to a better outcome of surgical procedures by reducing postoperative complications of SSI. Operating department professionals would benefit from clinical guidance and continuous training, highlighting the importance of persistent implementation of SSI preventive measures in everyday practice to improve the quality of care provided to surgical patients.


Assuntos
Antibioticoprofilaxia/normas , Cirurgiões/normas , Infecção da Ferida Cirúrgica/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oriente Médio , Fatores de Risco , Adulto Jovem
11.
J Sex Med ; 17(3): 461-469, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31918983

RESUMO

INTRODUCTION: Poor genital self-image is a common phenomenon leading to an increasing interest in female genital surgery over the last years. AIM: The aim was to correlate objective measurements of the labia minora with the individual subjective perception of the labial size. METHODS: In a cross-sectional study with 200 premenopausal women (median age 33.5 years) presenting for gynecological issues other than vulvar diseases, labial width and length were measured, and psychological and physical complaints were assessed. Multivariable logistic regression analyses were performed to identify factors that influenced self-reported complaints and subjective perception of labia size. MAIN OUTCOME MEASURE: The main outcome measure was labial appearance (width and length in mm, color), subjective perception of the labial size, and complaints. RESULTS: The median width of the labia minora was 19.0 mm (interquartile range = 12.6-27.5), and the median length was 35.5 mm (interquartile range = 27.8-48.9). The objective size of the labia was significantly associated with womens' subjective perception of the labial size, but not with self-reported complaints. Nearly one-third of the women (n = 53, 27%) reported complaints of their labia minora which were mainly physical (n = 41, 77%) or a combination of physical and psychological problems (n = 9, 17%), while only a small group reported experiencing only psychological complaints (n = 3, 6%). Predictors of complaints were previous cosmetic surgery and the subjective perception of the labia size. The latter was significantly associated with discomfort during intercourse and when visiting a sauna and by labia minora that protruded over the labia majora. CLINICAL IMPLICATIONS: Cutoff values to define labial hypertrophy and to justify labial reduction surgery should be avoided. STRENGTH & LIMITATIONS: This is a large sample of labial measurements in women not seeking labiaplasty. Standardized and validated questions regarding quality of life, sexuality, and body image could have provided more insight into psychological aspects. CONCLUSION: These data demonstrate the variability of labial anatomy and its perception. Widschwendter A, Riedl D, Freidhager K, et al. Perception of Labial Size and Objective Measurements-Is There a Correlation? A Cross-Sectional Study in a Cohort Not Seeking Labiaplasty. J Sex Med 2020;17:461-469.


Assuntos
Imagem Corporal , Qualidade de Vida , Vulva/anatomia & histologia , Adolescente , Adulto , Estudos de Coortes , Estudos Transversais , Feminino , Procedimentos Cirúrgicos em Ginecologia/métodos , Humanos , Hipertrofia/cirurgia , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Reconstrutivos/métodos , Vulva/cirurgia , Adulto Jovem
12.
Cell ; 179(7): 1537-1550.e19, 2019 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-31835032

RESUMO

Poxviruses encode a multisubunit DNA-dependent RNA polymerase (vRNAP) that carries out viral gene expression in the host cytoplasm. We report cryo-EM structures of core and complete vRNAP enzymes from Vaccinia virus at 2.8 Å resolution. The vRNAP core enzyme resembles eukaryotic RNA polymerase II (Pol II) but also reveals many virus-specific features, including the transcription factor Rap94. The complete enzyme additionally contains the transcription factor VETF, the mRNA processing factors VTF/CE and NPH-I, the viral core protein E11, and host tRNAGln. This complex can carry out the entire early transcription cycle. The structures show that Rap94 partially resembles the Pol II initiation factor TFIIB, that the vRNAP subunit Rpo30 resembles the Pol II elongation factor TFIIS, and that NPH-I resembles chromatin remodeling enzymes. Together with the accompanying paper (Hillen et al., 2019), these results provide the basis for unraveling the mechanisms of poxvirus transcription and RNA processing.

13.
BMC Womens Health ; 19(1): 165, 2019 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-31856794

RESUMO

BACKGROUND: Reliable contraception enables women and men to plan their family sizes and avoid unintended pregnancies, which can cause distress and anxiety, but also increase maternal mortality. This study explored potential barriers to contraceptive use for women in the Gaza Strip, Palestine from user and provider perspectives. METHODS: A convenient sample was used to recruit women, who were current contraception users, from three healthcare clinics that provide family planning care, two governmental and one non-governmental. A 16-item questionnaire was completed by 204 women, including socio-demographic data, contraceptive use and eight questions exploring user experience. Additionally, 51 women attended focus groups for a deeper insight into their contraceptive use experience and potential barriers. Furthermore, 14 healthcare providers were interviewed about their experience with service provision. Quantitative data are presented as means and frequencies and qualitative data were analysed item by item and are presented in themes jointly with the quantitative data. RESULTS: Women reported usage of only three main modern methods of contraception with 35.2% using intrauterine devices, 25.8% combined oral contraception and 16.4% condoms, while only 3.1% used the hormonal implant. Expectations from family planning services were low with most women attending the clinic having already decided their contraceptive method with decisions being made by husbands (41.2%) or women jointly with their partner (33.3%), only 13.7% took advice from service providers. Healthcare providers experienced high prevalence of beliefs that modern contraceptives cause infertility and cancer. Main barriers to effective family planning services were misconceptions of potential harm, poor availability and limited choice of contraceptive methods. CONCLUSION: Women's contraceptive choices in Gaza are limited by prevalent misconceptions and fears as well as recurring shortages, negatively impacting fertility control. Men are a major factor in choosing a contraceptive method, however, they have limited access to information and therefore, potentially more misconceptions. Therefore, male community members need to be included in the delivery of information on contraceptives to increase women's choice. Furthermore, greater access to long-acting reversible contraceptives, such as the hormonal implant, and improved availability might be key factors in improving contraceptive uptake in Gaza and, thus, reducing unintended pregnancies.


Assuntos
Comportamento de Escolha , Comportamento Contraceptivo/psicologia , Anticoncepção/psicologia , Pessoal de Saúde/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Adulto , Anticoncepção/estatística & dados numéricos , Comportamento Contraceptivo/estatística & dados numéricos , Utilização de Instalações e Serviços/estatística & dados numéricos , Serviços de Planejamento Familiar , Feminino , Grupos Focais , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Oriente Médio , Gravidez , Gravidez não Planejada/psicologia , Pesquisa Qualitativa , Inquéritos e Questionários , Adulto Jovem
14.
Nat Commun ; 10(1): 5138, 2019 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-31723136

RESUMO

Cytochrome bd oxidases are terminal reductases of bacterial and archaeal respiratory chains. The enzyme couples the oxidation of ubiquinol or menaquinol with the reduction of dioxygen to water, thus contributing to the generation of the protonmotive force. Here, we determine the structure of the Escherichia coli bd oxidase treated with the specific inhibitor aurachin by cryo-electron microscopy (cryo-EM). The major subunits CydA and CydB are related by a pseudo two fold symmetry. The heme b and d cofactors are found in CydA, while ubiquinone-8 is bound at the homologous positions in CydB to stabilize its structure. The architecture of the E. coli enzyme is highly similar to that of Geobacillus thermodenitrificans, however, the positions of heme b595 and d are interchanged, and a common oxygen channel is blocked by a fourth subunit and substituted by a more narrow, alternative channel. Thus, with the same overall fold, the homologous enzymes exhibit a different mechanism.


Assuntos
Grupo dos Citocromos b/química , Grupo dos Citocromos b/metabolismo , Complexo de Proteínas da Cadeia de Transporte de Elétrons/química , Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/metabolismo , Escherichia coli/enzimologia , Oxirredutases/química , Oxirredutases/metabolismo , Homologia de Sequência de Aminoácidos , Grupo dos Citocromos b/ultraestrutura , Complexo de Proteínas da Cadeia de Transporte de Elétrons/ultraestrutura , Proteínas de Escherichia coli/ultraestrutura , Geobacillus/enzimologia , Heme/química , Heme/metabolismo , Modelos Moleculares , Oxirredutases/ultraestrutura , Oxigênio/metabolismo , Prótons , Especificidade por Substrato , Ubiquinona/química , Ubiquinona/metabolismo , Água
15.
Nature ; 576(7786): 321-325, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31597161

RESUMO

Host infection by pathogenic mycobacteria, such as Mycobacterium tuberculosis, is facilitated by virulence factors that are secreted by type VII secretion systems1. A molecular understanding of the type VII secretion mechanism has been hampered owing to a lack of three-dimensional structures of the fully assembled secretion apparatus. Here we report the cryo-electron microscopy structure of a membrane-embedded core complex of the ESX-3/type VII secretion system from Mycobacterium smegmatis. The core of the ESX-3 secretion machine consists of four protein components-EccB3, EccC3, EccD3 and EccE3, in a 1:1:2:1 stoichiometry-which form two identical protomers. The EccC3 coupling protein comprises a flexible array of four ATPase domains, which are linked to the membrane through a stalk domain. The domain of unknown function (DUF) adjacent to the stalk is identified as an ATPase domain that is essential for secretion. EccB3 is predominantly periplasmatic, but a small segment crosses the membrane and contacts the stalk domain. This suggests that conformational changes in the stalk domain-triggered by substrate binding at the distal end of EccC3 and subsequent ATP hydrolysis in the DUF-could be coupled to substrate secretion to the periplasm. Our results reveal that the architecture of type VII secretion systems differs markedly from that of other known secretion machines2, and provide a structural understanding of these systems that will be useful for the design of antimicrobial strategies that target bacterial virulence.


Assuntos
Microscopia Crioeletrônica , Mycobacterium smegmatis/química , Sistemas de Secreção Tipo VII/química , Sistemas de Secreção Tipo VII/ultraestrutura , Actinobacteria/química , Actinobacteria/enzimologia , Adenosina Trifosfatases/química , Adenosina Trifosfatases/isolamento & purificação , Adenosina Trifosfatases/ultraestrutura , Trifosfato de Adenosina/metabolismo , Modelos Moleculares , Mycobacterium smegmatis/enzimologia , Mycobacterium smegmatis/ultraestrutura , Domínios Proteicos , Estrutura Quaternária de Proteína , Subunidades Proteicas/química , Subunidades Proteicas/isolamento & purificação , Relação Estrutura-Atividade , Sistemas de Secreção Tipo VII/isolamento & purificação
16.
Eur J Psychotraumatol ; 10(1): 1654063, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31497261

RESUMO

Background: Domestic violence (DV) is a widespread yet commonly underdetected problem with severe impact on physical and mental health. To date, only limited information is available on prevalence and detection-rates of victims of DV in hospital settings. Objective: The aim of this study was (a) to assess the prevalence and impact of DV on physical and mental health as well as risk-factors associated with it, (b) to determine how many patients had been asked directly about DV in the hospital and (c) to investigate patients' preferences about being asked about DV in a hospital setting. Methods: Adult inpatients and outpatients at seven somatic departments at the University Hospital Innsbruck (Austria) were included consecutively in this ad-hoc, cross-sectional paper-and-pencil questionnaire-based study. In total, n = 2,031 patients were assessed regarding their experiences with DV. They also reported on whether they had been asked about DV at the hospital and whether they would mind being asked about it. To evaluate the impact of DV on patients' self-reported physical and mental health, odds ratios were calculated using binary logistic regression. Results: DV was reported by 17.4% of patients, with 4.0% indicating current DV exposure. Lifetime DV exposure was associated with a significant risk for both physical and mental health-problems. Only 4.8% of patients with DV exposure had ever been asked about it by hospital staff. While patients with a history of DV were more open to being asked about DV than patients without DV (78.2% vs. 72.9%), overall acceptance was still high (74%). Conclusion: DV is a frequently overlooked problem with detrimental effects on physical and mental health. While high acceptance of DV assessment was found, only a small proportion of affected patients had indeed been assessed for DV. Screening for DV in hospitals may thus increase the number of identified patients.

17.
Vitam Horm ; 111: 247-279, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31421703

RESUMO

More than 40years ago, the endogenous opioids were first described. Their role as important neuromodulators of pain and their influence on a variety of neuroendocrine control systems within the central nervous system has been recognized. More recently, endogenous opioids and their receptor have been identified in a variety of reproductive and non-reproductive tissues outside the central nervous system. What role the opioid system plays in these peripheral tissues and organs is not completely understood and thus the subjects of current research. In the central nervous system, endogenous opioids inhibit pulsatile Gonadotropin Releasing Hormone (GnRH) release, affecting the release of gonadotropins from the pituitary, and thus mediating stress response within the central nervous-pituitary-gonadal axes in both women and men-Peripherally, endogenous opioids have been demonstrated to be present-among other organs-in the pancreas and in the ovary, where they are produced by granulosa cells and may influence oocyte maturation. In men, endogenous opioids play a role in sperm production within the testis. Opioid antagonists such as naltrexone have been used to restore cyclicity in women through improvement in insulin resistance, GnRH-pulsatility and hyperandrogenemia stemming from specific pathophysiological conditions such as hypothalamic amenorrhea, polycystic ovarian syndrome, hyperinsulinemia, ovarian hyperstimulation syndrome. Opioid antagonists have also been used to treat male sexual disorders and male infertility. In summary, endogenous opioids exert a variety of actions within the reproductive system which are reviewed in this chapter.


Assuntos
Analgésicos Opioides/farmacologia , Peptídeos Opioides/fisiologia , Reprodução/efeitos dos fármacos , Reprodução/fisiologia , Amenorreia/etiologia , Amenorreia/fisiopatologia , Animais , Endorfinas/fisiologia , Feminino , Humanos , Doenças Hipotalâmicas/complicações , Doenças Hipotalâmicas/fisiopatologia , Masculino , Peptídeos Opioides/antagonistas & inibidores , Ocitocina/fisiologia , Síndrome do Ovário Policístico/fisiopatologia , Gravidez , Prolactina/fisiologia , Receptores Opioides/fisiologia
18.
BMJ Open ; 9(8): e026788, 2019 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-31383695

RESUMO

OBJECTIVES: This study examined the attitudes of nurses and doctors to key patient safety concepts, evaluated differences and similarities between professional groups and assessed positive and negative attitudes to identify target areas for future training. SETTING: Four major governmental hospitals in the Gaza-Strip. PARTICIPANTS: A convenience sample of 424 nurses and 150 physicians working for at least 6 months in the study hospitals. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measures were mean scores with SD as measured for individual items and nine main patient safety domains assessed by the Attitudes to Patient Safety Questionnaire. Secondary outcome measures were the proportions of doctors and nurses, that gave a positive response to each item, represented as percentage of each group. RESULTS: Nurses and doctors held moderately positive attitudes towards patient safety with five out of nine domain scores >3.5 of 5. Doctors showed slightly more positive attitudes than nurses, despite a smaller proportion of doctors having received patient safety training with 37.5% compared with 41.9% of nurses. Both professions displayed their most positive patient safety attitudes in the same domains ('team functioning' and 'working hours as a cause for error'), as well as their two most negative attitudes ('importance of patient safety in the curriculum' and 'professional incompetence as a cause of error'), demonstrating significant deficits in understanding medical errors. A specific challenge will be the negative attitudes of both professions towards patient safety training for wider dissemination of this content in the postgraduate curriculum. CONCLUSION: Patient safety attitudes were moderately positive in both professional groups. Target of future patient safety training should be enhancing the understanding of error in medicine. Any training has to be motivating and relevant for clinicians, demonstrating its importance in ongoing professional learning.

19.
BMC Health Serv Res ; 19(1): 550, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31387582

RESUMO

BACKGROUND: Providing safe care helps to reduce mortality, morbidity, length of hospital stay and cost. Patient safety is highly linked to attitudes of health care providers, where those with more positive attitudes achieve higher degrees of patient safety. This study aimed to assess attitudes of nurses working in governmental hospitals in the Gaza-Strip toward patient safety and to examine factors impacting their attitudes. METHODS: This is a cross-sectional, descriptive study with a convenient sample of 424 nurses, working in four governmental hospitals. The Attitudes to Patient Safety Questionnaire III, a validated tool consisting of 29 items that assesses patient safety attitudes across nine main domains, was used. RESULTS: Nurses working in governmental hospitals showed overall only slightly positive attitudes toward patient safety with a total score of 3.68 on a 5-point Likert scale, although only 41.9% reported receiving patient safety training previously. The most positive attitudes to patient safety were found in the domains of 'working hours as a cause of error' and 'team functioning' with scores of 3.94 and 3.93 respectively, whereas the most negative attitudes were found in 'importance of patient safety in the curriculum' with a score of 2.92. Most of the study variables, such as age and years of experience, did not impact on nurses' attitudes. On the other hand, some variables, such as the specialty and the hospital, were found to significantly influence reported patient safety attitudes with nurses working in surgical specialties, showing more positive attitudes. CONCLUSION: Despite the insufficient patient safety training received by the participants in this study, they showed slightly positive attitudes toward patient safety with some variations among different hospitals and departments. A special challenge will be for nursing educators to integrate patient safety in the curriculum, as a large proportion of the participants did not find inclusion of patient safety in the curriculum useful. Therefore, this part of the curriculum in nurses' training should be targeted and developed to be related to clinical practice. Moreover, hospital management has to develop non-punitive reporting systems for adverse events and use them as an opportunity to learn from them.


Assuntos
Atitude do Pessoal de Saúde , Enfermeiras e Enfermeiros/psicologia , Segurança do Paciente/normas , Gestão da Segurança/normas , Adulto , Árabes , Estudos Transversais , Feminino , Política de Saúde , Hospitais Públicos , Humanos , Masculino , Pessoa de Meia-Idade , Oriente Médio , Enfermeiras e Enfermeiros/normas , Gestão da Segurança/organização & administração , Inquéritos e Questionários
20.
J Mol Biol ; 431(17): 3081-3090, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31291591

RESUMO

Since life has emerged, gradients of osmolytes over the cell membrane cause pressure changes in the cell and require tight regulation to prevent cell rupture. The mechanosensitive channel of small conductance (MscS) releases solutes and water when a hypo-osmotic shock raises the pressure in the cell. It is a member of a large family of MscS-like channels found in bacteria, archaea, fungi and plants and model for mechanosensation. MscS senses the increase of tension in the membrane directly by the force from the lipids, but the molecular mechanism is still elusive. We determined the lipid interactions of MscS by resolving the structure of Escherichia coli MscS embedded in membrane discs to 2.9-Å resolution using cryo-electron microscopy. The membrane is attached only to parts of the sensor paddles of MscS, but phospholipid molecules move through grooves into remote pockets on the cytosolic side. On the periplasmic side, a lipid bound by R88 at the pore entrance is separated from the membrane by TM1 helices. The N-terminus interacts with the periplasmic membrane surface. We demonstrate that the unique membrane domain of MscS promotes deep penetration of lipid molecules and shows multimodal interaction with the membrane to fine-tune tension sensing.

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