Development and Validation of Performance-Based Assessment of Daily Living Tasks in Age-Related Macular Degeneration.

Purpose: To establish the reliability and validity of five performance-based activities of daily living task tests (ADLTT), to correlate structure to function, to evaluate the impact of visual impairment (VI) on age-related macular degeneration (AMD), and to develop new outcome measures. Methods: A multidisciplinary team developed five ADLTTs: (1) reading test (RT); (2) facial expression (FE) recognition; (3) item search (IS) task; (4) money counting (MC) task; and (5) making a drink (MD), tested with binocular and monocular vision. ADLTTs were tested for known-group (i.e., difference between AMD group and controls) and convergent (i.e., correlation to other measures of visual function), validity metrics, and test-retest reliability in 36 patients with VI (visual acuity (logMAR VA > 0.4) in at least one eye caused by AMD versus 36 healthy controls without VI. Results: Compared to controls, AMD patients had a slower reading speed (-77.41 words/min; P < 0.001); took longer to complete MC using monocular worse eye and binocular vision (15.13 seconds and 4.06 seconds longer compared to controls, respectively; P < 0.001); and MD using monocular worse eye vision (9.37 sec; P = 0.033), demonstrating known-group validity. Only RT and MC demonstrated convergent validity, showing correlations with VA, contrast sensitivity, and microperimetry testing. Moderate to good test-retest reliability was observed for MC and MD (interclass correlation coefficient = 0.55 and 0.77; P < 0.001) using monocular worse eye vision. Conclusions: Real-world ADL functioning associated with VI-related AMD can be assessed with our validated ADLTTs, particularly MC and MD. Translational Relevance: This study validates visual function outcome measures that are developed for use in future clinical practice and clinical trials.

Clinical research advances of CFHR5 nephropathy: a recent review.

CFHR5 nephropathy is a type of clinical C3 glomerulopathy, which is a monogenic genetic disease caused by the internal replication of CFHR5 gene, a protein related to the complement regulatory factor H family. The disease seems to be prevalent only in people of Greek Cypriot descent. Because of the special variation of the internal replication of exon 2 and exon 3 of CFHR5 protein in the occurrence of disease, it has had a serious impact on local residents. At present, the mechanism of glomerular damage caused by CFHR5 protein mutations is still unclear. The purpose of this article is to review the clinical research advances of this disease in the past 10 years, including the study of mutant genes, the analysis of mutant proteins and the role of alternative pathways in glomerular injury. It covers the progress in diagnosis and clinical treatment of the disease and looks forward to the future development prospects of its treatment. It is hoped that the recent results will be summarized for the follow-up in-depth study of CFHR5 nephropathy.

[Development and implementation of common data sets for venous thromboembolism: current situation and application prospects].

Venous thromboembolism (VTE) is a formidable disease that poses a serious threat to the health and well-being of hospitalized patients. Owing to its high incidence, debilitating morbidity, and alarming mortality rates, VTE has gained increasing attention from the clinical medicine community worldwide. Unfortunately, the current state of clinical prevention and treatment of VTE is not very optimistic, necessitating the establishment of large disease-specific databases and real-world studies, which can accumulate effective evidence-based medical evidence to gradually standardize the clinical prevention and treatment and quality control of VTE. The construction and development of large medical databases depend greatly on standardized datasets, which establish the conceptual data models of VTE through data standardization routes, set the object classes according to the model, define the attributes of the classes, standardize the data types and property values, and organize the standardized data elements. This article focuses on providing an in-depth overview of the unique characteristics of various domestic and foreign VTE datasets, describing their application and research progress in VTE, as well as the role of datasets in standardizing clinical and research practices to strengthen quality control and artificial intelligence. Through this comprehensive discussion, we hope to promote the establishment of VTE datasets and enable their use in high-quality large real-world studies.

[Awareness and management of chronic thromboembolic pulmonary hypertension among respiratory physicians revealed by a questionnaire analysis].

Objective: To evaluate the awareness and management status of chronic thromboembolic pulmonary hypertension (CTEPH) among respiratory physicians and therefore to provide for establishing clinical guidelines on CTEPH. Methods: A questionnaire was designed to address the common questions in CTEPH management. The responses were collected online and the data were analyzed. Totally, 1 038 valid questionnaires were collected. Results: 74.1% of the responders were from tertiary hospitals and 88.5% were attending physicians. Only a few hospitals could carry out ventilation-perfusion scintigraphy (31.3%) and right heart catheterization (38.5%). For the treatment of CTEPH, pulmonary endarterectomy and balloon pulmonary angioplasty (BPA) were only performed in 8.0% and 10.4% of the hospitals respectively, and mostly in tertiary hospitals, P<0.01. 49.6% of the physicians were familiar with the interpretation of CTPA, while only 19.9% of V/Q scan. 88.5% of the physicians choose CTPA as the screening tool for CTEPH, but only 3.9% were consistent with the guidelines. 79% of the physicians agreed with lifelong anticoagulation for CTEPH, and 70.8% supported operability should be evaluated in all CTEPH patients. Conclusions: This questionnaire study showed that there was a gap between the guidelines and the real world practice in CTEPH management. Efforts should be made to improve the awareness and standardization of the management of CTEPH.

[Risk factors and clinical features of hospital-associated venous thromboembolism].

Objective: To investigate the clinical features and risk factors of hospital-associated venous thromboembolism (VTE). Methods: The study enrolled acute VTE patients admitted into China-Japan Friendship Hospital from January 1, 2017 to December 31, 2017. The hospital-associated VTE (HA-VTE) group and the community-associated VTE (CA-VTE) group were classified according to whether the VTE occurred during hospitalization or within a 90-day period of admission to hospital (including inpatient with at least two days of hospital stay or a surgical procedure under general or regional anaesthesia). Differences in clinical features, risk factors, and mortality rate were compared between the two groups. Results: A total of 437 patients with acute VTE were analyzed in the study. Among them, 266 patients were HA-VTE, 171 patients were CA-VTE. Patients in the CA-VTE group were more likely to have varicose veins, sedentary, long-distance travel, and patients in the HA-VTE group were more complicated with recent surgery (<1 month), bed rest, active malignant tumor, acute infections, acute cerebral infarction, fracture, central venous catheter (P<0.05). The CA-VTE group had more clinical symptoms such as lower extremity pain, dyspnea, chest pain and chest tightness (P<0.05). HA-VTE patients had less clinical symptoms but were more severe than the CA-VTE patients, with more sudden deaths (0 vs 3.4%, P=0.035). Among HA-VTE patients, 92.8% experienced VTE during hospitalization or within 1 month of the preceding hospital encounter, with a 13-day median time to VTE. The all-cause mortality rate was higher for HA-VTE group than CA-VTE group (8.3% vs 1.2%, P<0.001), and the in-hospital VTE was more common compared to VTE diagnosed post-discharge (12.2% vs 3.4%, P<0.001). Conclusions: More than half events of VTE are related to recent hospitalizations. HA-VTE has different risk factors from CA-VTE, combined with fewer clinical symptoms but higher all-cause mortality rate. More attention about VTE should be paid to hospitalized patients to reduce the incidence of HA-VTE events.

Organization and roles of nucleosomes at mouse meiotic recombination hotspots.

Meiotic double strand breaks (DSBs) occur at discrete regions in the genome coined hotspots. Precisely what directs site selection of these DSBs is hotly debated and in particular it is unclear which chromatin features, and regulatory factors are necessary for a genomic region to initiate and resolve DSBs as a crossover (CO) event. In human and mouse, one layer of hotspot selection control is a recognition sequence element present at these sites that is bound by the Prdm9 zinc-finger protein. Furthermore, an overall open chromatin structure is thought to be required to allow access of the recombination machinery, and this is often dictated by the packaging of DNA around nucleosomes. We recently defined the nucleosome occupancy maps of four mouse recombination hotspots throughout meiosis. These analyses revealed no obvious dynamic changes in nucleosome occupancy, suggesting an intrinsic nature of recombinogenic sites, yet they also revealed that nucleosomes define zones of exclusion for CO resolution. Here, we discuss new evidence implicating nucleosome occupancy in recombinogenic repair and its potential roles in controlling chromatin structure at mouse meiotic hotspots.

Nucleosome occupancy landscape and dynamics at mouse recombination hotspots.

During meiosis, paternal and maternal homologous chromosomes recombine at specific recombination sites named hotspots. What renders 2% of the mammalian genomes permissive to meiotic recombination by allowing Spo11 endonuclease to initiate double-strand breaks is largely unknown. Work in yeast has shown that chromatin accessibility seems to be important for this activity. Here, we define nucleosome profiles and dynamics at four mouse recombination hotspots by purifying highly enriched fractions of meiotic cells. We found that nucleosome occupancy is generally stable during meiosis progression. Interestingly, the cores of recombination hotspots have largely open chromatin structure, and the localization of the few nucleosomes present in these cores correlates precisely with the crossover-free zones in recombinogenic domains. Collectively, these high-resolution studies suggest that nucleosome occupancy seems to direct, at least in part, how meiotic recombination events are processed.

Anatomy of mouse recombination hot spots.

Genome-wide analyses have suggested thousands of meiotic recombination hot spots across mammalian genomes. However, very few hot spots have been directly analyzed at a sub-kb scale for crossover (CO) activity. Using recombinant inbred strains as a CO library, here we report the identification and detailed characterization of seven new meiotic hot spots on mouse chromosome 19, more than doubling the number of currently available mouse hot spots. Although a shared feature is the narrow 1.5-2.5-kb width of these recombinogenic sites, these analyses revealed that hot spots have diverse sequence attributes and distinct symmetric and asymmetric CO profiles. Interestingly, CO molecules with discontinuous conversion tracts are commonly observed, contrasting with those found in human. Furthermore, unlike human hot spots, those present in the mouse do not necessarily have a quasi-normal CO distribution but harbor CO repulsion zones within recombinogenic cores. We propose a model where local chromatin landscape directs these repulsion zones.

A Global Expression Switch Marks Pachytene Initiation during Mouse Male Meiosis.

Male spermatogenesis is an essential and complex process necessary to gain totipotency and allow a whole new organism to develop upon fertilization. While single-gene based studies have provided insights into the mechanisms underlying spermatogenesis, detailed global profiling of all the key meiotic stages is required to fully define these processes. Here, by isolating highly enriched mouse meiotic cell populations, we have generated a comprehensive gene expression atlas of mammalian meiosis. Our data define unique signatures for the specific stages of meiosis, including global chromosome X inactivation and reactivation. The data also reveal profound switches in global gene expression at the initiation of pachynema that are reminiscent of the commitment to meiosis observed in budding yeast. Overall, this meiotic atlas provides an exhaustive blueprint and resource for mammalian gametogenesis and meiosis.

Production of gamma-linolenic acid by disrupted mycelia of Mortierella isabellina.

AIMS: To optimize the production of linolenic acid by disrupted mycelia of Mortierella isabellina. METHODS AND RESULTS: Effects of incubation conditions such as incubation time, pH of reaction mixture, concentration of Mg2+ or malate and incubation temperature on production of linolenic acid were studied. The production of gamma-linolenic acid reached 224 mg g-1 dry cells when the reaction mixture was composed of 1.0 g (dry mycelial mass) of disrupted mycelia of M. isabellina, 50 ml (50 mmol l(-1)) potassium phosphate buffer supplemented with 0.312 mmol l(-1) of Mg2+ and 10 mmol l(-1) of malate, pH 7.0 and incubated at 5 degrees C for 1 day. CONCLUSIONS: Incubation temperature, concentration of Mg2+ and malate showed major effects on the increased linolenic acid production. SIGNIFICANCE AND IMPACT OF THE STUDY: This study highlights conditions for increasing gamma-linolenic acid production by cell-free mycelia of M. isabellina and an insight into rapidly gaining high production of polyunsaturated fatty acids.

Production of gamma-linolenic acid by Mortierella isabellina grown on hexadecanol.

AIMS: To optimize the production of linolenic acid by Mortierella isabellina grown on hexadecanol. METHODS AND RESULTS: Effects of culture conditions such as culture time, pH of medium, hexadecanol concentration, incubation temperature and ageing of mycelia on production of linolenic acid were studied. The production of gamma-linolenic acid reached 2.44 mg ml-1 (271 mg g-1 dry cells) when Mortierella isabellina was cultivated in a medium consisting of 2% hexadecanol and 1% yeast extract at 23 degrees C for 120 h and then the mycelia, after removal of medium by suction filtration, were allowed to stand for a further 15 d at 5 degrees C. CONCLUSION: Ageing of mycelia and incubation temperature showed predominant effects on the increased linolenic acid production. SIGNIFICANCE AND IMPACT OF THE STUDY: This study highlights effective conditions for increasing linolenic acid production by Mortierella isabellina grown on hexadecanol.