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Introduction: The landscape of poly (ADP-ribose) polymerase (PARP) inhibition in ovarian cancer is rapidly evolving and becoming increasingly complex. Ovarian cancer is leading therapeutic innovation by providing the proof of concept for DNA repair as a target. Three different PARP inhibitors have now received approvals in the US and Europe in different indications. Subtle but crucial differences can be found among the licensed indications for each PARP inhibitor in terms of histology, type of BRCA mutation (germline and/or somatic), number of prior lines of chemotherapy and whether the indication is in the treatment or maintenance settings.

Areas covered: We review the latest clinical data regarding the PARP inhibitor rucaparib in ovarian cancer, provide an update on the evolving landscape of PARP inhibition in ovarian cancer, and summarize avenues of ongoing and future research.

Expert opinion: All eligible patients should be offered a PARP inhibitor. SOLO1 trial results demonstrated an unprecedented benefit maintenance with PARP inhibitors in first line. Results from trials evaluating PARP inhibitors as maintenance in first line regardless of BRCA status and from trials evaluating combinatorial strategies are eagerly awaited.  相似文献   

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Graefe's Archive for Clinical and Experimental Ophthalmology - The published online version contains mistake as the author's first name and last name have been interchanged as "Hild...  相似文献   
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Background

There are well-established relationships between health and homelessness, and shelters can facilitate the transmission of diseases and contribute to their prevention. Adequate environmental health conditions and hygiene behaviors in homeless shelters are fundamental to the health of their clients, a marginalized population. We report the status of environmental health conditions and hygiene behaviors in homeless shelters and associated health outcomes; interventions to improve these conditions, behaviors, and outcomes; and obstacles to improvement.

Methods

PubMed, Web of Science, Scopus, and EBSCOhost were searched for peer-reviewed studies, and additional sources for grey literature. Studies were included if they reported primary data on one or more environmental health condition or hygiene behavior in homeless shelters.

Results

Twenty-eight studies were included in the review. Insufficient ventilation systems, unhygienic bedding, and overcrowding were the most documented environmental health and hygiene deficiencies in homeless shelters, and tuberculosis infections and skin diseases were the most documented associated health outcomes among clients. Studies frequently recommended or described implementation of behavioral and administrative controls, ventilation system improvements, and ultraviolet germicidal irradiation fixtures.

Discussion

Most studies addressed airborne transmission of tuberculosis and were conducted in high-income countries, revealing an imbalance in the literature. Insufficient resources and the transience of clients are barriers to improving hygiene behaviors and environmental conditions in homeless shelters. Further investment and research into ensuring adequate hygiene and environmental health in this setting can protect and promote the health and well-being of people experiencing homelessness.  相似文献   
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Objective

To examine whether a healthy weight intervention embedded in the Parents as Teachers (PAT) home visiting program, which was previously found to improve mothers’ body mass index (BMI) and obesity-related behaviors, changed the BMI of preschool children or maternal feeding practices.

Methods

This stratified randomized trial included preschool-aged children at risk for overweight whose mothers were overweight or had obesity (n?=?179). The Healthy Eating and Active Living Taught at Home (HEALTH) intervention was based on the Diabetes Prevention Program. Differences were examined using repeated-measures mixed-ANOVA models.

Results

Compared with PAT usual care, the HEALTH intervention had no effect on children's BMI or maternal feeding practices. However, combined analyses showed that children's BMI percentile decreased (P??=?.007), BMI z-scores were maintained (P??=?.19), and 3 of 8 feeding practices improved over time (P < .05).

Conclusions and Implications

Additional research is needed to assess the effectiveness of PAT to prevent preschool-age obesity using rigorous designs (eg, group-randomized trials) and to identify its active components. HEALTH is ready to be scaled up to prevent maternal weight gain through embedding within the national PAT program.  相似文献   
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Coxiella burnetii is an obligate intracellular Gram-negative bacterium that causes the zoonotic disease Q fever. Although Q fever is mainly transmitted by aerosol infection, study of the immune responses in the lung following pulmonary C. burnetii infection is lacking. Neutrophils are considered the first immune cell to migrate into the lung and play an important role in host defense against aerosol infection with microbial pathogens. However, the role of neutrophils in the host defense against C. burnetii infection remains unclear. To determine the role of neutrophils in protective immunity against C. burnetii infection, the RB6-8C5 antibody was used to deplete neutrophils in mice before intranasal infection with C. burnetii. The results indicated that neutrophil-depleted mice developed more severe disease than their wild-type counterparts, suggesting that neutrophils play an important role in host defense against C. burnetii pulmonary infection. We also found that neither CXC chemokine receptor 2 (CXCR2) nor interleukin-17 (IL-17) receptor (IL-17R) deficiency changed the severity of disease following intranasal C. burnetii challenge, suggesting that keratinocyte-derived chemokine and IL-17 may not play essential roles in the response to C. burnetii infection. However, significantly higher C. burnetii genome copy numbers were detected in the lungs of IL-1R−/− mice at 14 days postinfection. This indicates that IL-1 may be important for the clearance of C. burnetii from the lungs following intranasal infection. Our results also suggest that neutrophils are involved in protecting vaccinated mice from C. burnetii challenge-induced disease. This is the first study to demonstrate an important role for neutrophils in protective immunity against C. burnetii infection.  相似文献   
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A 48-year-old smoker with a history of hyperthyroidism treated 10 years prior to presentation with radioactive iodine ablation of the thyroid gland presented to his ophthalmologist with a 2-week history of transient loss of vision in the right eye occurring for 1 to 2 hours each morning. He denied ocular pain, diplopia or change in the prominence of one or both eyes. Examination revealed 2 mm of relative proptosis on the right, bilateral temporal flare and lower lid retraction. There was minimal upper lid retraction and no evidence of lid lag. Ocular motility was full. Dilated fundoscopic examination revealed bilateral optic nerve edema, right more than left. CT of the orbit demonstrated enlargement of the extraocular muscles bilaterally with marked enlargement of the right medial rectus and left inferior rectus muscles resulting in crowding at the orbital apex bilaterally. Laboratory testing revealed the patient to be hyperthyroid. The patient was treated with high dose oral steroids followed by orbital radiation. Hyperthyroidism was managed by the patient’s primary care physician. Visual symptoms rapidly improved with oral steroids and orbital radiation. Optic nerve edema completely resolved. Repeat CT imaging demonstrated a reduction in the enlargement of the extraocular muscles with relief of bilateral optic nerve compression.  相似文献   
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