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Background: Ustekinumab, a human immunoglobulin G1 monoclonal antibody that binds to and inhibits interleukin (IL)-12/IL-23, is indicated for multiple immune-mediated diseases. Ustekinumab is actively transported across the placenta and theoretically could impact pregnancy outcomes. Limited data on pregnancy outcomes with ustekinumab exposure are available. Aim: To assess pregnancy outcomes in patients exposed to ustekinumab during pregnancy. Methods: Cumulative data on medically confirmed ustekinumab-exposed pregnancies from the manufacturer's Global Safety Database were summarised. Descriptive data for pregnancy outcomes were presented overall and by patient subgroups. Results: As of 31 August 2020, 408 medically confirmed, prospective, maternal ustekinumab-exposed pregnancies with reported outcomes were identified. The mean maternal age was 31 years. Of the 420 pregnancy outcomes (including 4 sets of twins),a,b 340 (81%) were live births, 51 (12.1%) spontaneous abortions, 25 (6%) elective/induced abortions, 3 (0.7%) stillbirths and 1 (0.2%) ongoing pregnancy with foetal congenital anomaly (CA). Among 340 live births, 33 (9.7%) were born pre-term. The rate of major CAs was similar by indication (Crohn's disease vs psoriasis), ustekinumab dose (45 mg vs 90 mg) and timing and duration of maternal exposure to ustekinumab. Prospective outcomes of pregnancies with paternal periconceptional ustekinumab exposure (n = 87) included 92% live births (1.2% major CA), 5.7% spontaneous abortions and 2.3% elective/induced abortions. Conclusions: Rates of adverse pregnancy outcomes or CAs with ustekinumab exposure were consistent with rates reported for the US general population and do not suggest a higher risk associated with maternal or paternal exposure to ustekinumab.

A survey was conduct to analyze the usage situation of post-exposure prophylaxis(PEP) and related factors among men who have sex with men(MSM) in 6 cities of Shandong Province. Total of 2 620 subjects, the use ratio was 2.98% (78/2 620). Compared with age≤24 years,monthly income5 000 yuan,non-commercial sex, non-DU,non-STD,role for being insert in the anal intercourse,MSM was more likely to use PEP with age≥45 years(对山东省某6个地市招募的2 620名男男性行为者（MSM）进行调查，分析MSM人群HIV暴露后预防（PEP）的使用状况及相关影响因素。MSM人群整体PEP使用比例为2.98%（78/2 620），不同年龄、月收入水平、商业性行为发生状况、吸食新型毒品状况、性病患病状况、性行为角色的MSM人群其PEP使用比例差异具有统计学意义（

OBJECTIVE: To describe the distribution characteristics of inflammatory bowel disease among permanent residents in Yinzhou District, Ningbo City, and to understand the disease burden and development trend of inflammatory bowel disease in this area. METHODS: Using the retrospective cohort design, we collected the registration information of all permanent residents in the residents' health files of the Yinzhou Regional Health Information Platform from 2010 to 2020, and used electronic medical records to follow up their inflammatory bowel disease visits. A one-year wash-out period was set, and the patients who were diagnosed with the primary diagnosis for the first time after one year of registration were re-garded as new cases. The incidence density and 95% confidence interval (CI) of inflammatory bowel disease were estimated by Poisson distribution. RESULTS: From 2011 to 2020, a total of 1 496 427 permanent residents in Yinzhou District were included, of which 729 996 were male (48.78%). The total follow-up person-years were 8 081 030.82, and the median follow-up person-years were 5.41 [interquartile range (IQR): 5.29]. During the study period, there were 1 217 new cases of inflammatory bowel disease, of which males (624 cases, 51.27%) were more than females (593 cases, 48.73%). The total incidence density was 15.06/100 000 person-years (95%CI: 14.23, 15.93). Among all new cases, there were 1 106 cases (90.88%) of ulcerative colitis, with an incidence density of 13.69 per 100 000 person-years (95%CI: 12.89, 14.52); 70 cases (5.75%) of Crohn's disease, with an incidence density of 0.87 per 100 000 person-years (95%CI: 0.68, 1.09); and 41 cases (3.37%) of indeterminate colitis, with an incidence density of 0.51 per 100 000 person-years (95%CI: 0.36, 0.69). The median age of onset of ulcerative colitis was 50.82 years old (IQR: 18.77), with the highest proportion (15.01%) in the 45-49 years group. The incidence density of ulcerative colitis gradually increased with age, reaching a relatively high level in the 45-49 years group (20.53/100 000 person-years; 95%CI: 17.63, 23.78), followed by a slight increase. And the incidence density in the 65-69 years group was the highest (25.44/100 000 person-years; 95%CI: 20.85, 30.75), with a rapid decrease in the 75-79 years group. The median age of onset of Crohn's disease was 44.34 years (IQR: 33.41), with the highest proportion (12.86%) in the 25-29 years group. Due to the small number of new cases of Crohn's disease, the age distribution fluctuated greatly, with peaks both in young and old people. From 2011 to 2020, the incidence density of inflammatory bowel disease in Yinzhou District was at a low level from 2011 to 2013, and showed a rapid upward trend from 2014 to 2016, reaching a peak of 24.62 per 100 000 person-years in 2016 (95%CI: 21.31, 28.30), and slightly decreased in 2017—2020. CONCLUSION: The incidence density of inflammatory bowel disease in Yinzhou District from 2011 to 2020 was at a relatively high level, and medical institutions and health departments need to pay attention to the burden of disease caused by it.

Nature experiences have been linked to mental and physical health. Despite the importance of understanding what determines individual variation in nature experience, the role of genes has been overlooked. Here, using a twin design (TwinsUK, number of individuals = 2,306), we investigate the genetic and environmental contributions to a person’s nature orientation, opportunity (living in less urbanized areas), and different dimensions of nature experience (frequency and duration of public nature space visits and frequency and duration of garden visits). We estimate moderate heritability of nature orientation (46%) and nature experiences (48% for frequency of public nature space visits, 34% for frequency of garden visits, and 38% for duration of garden visits) and show their genetic components partially overlap. We also find that the environmental influences on nature experiences are moderated by the level of urbanization of the home district. Our study demonstrates genetic contributions to individuals’ nature experiences, opening a new dimension for the study of human–nature interactions., Nature experiences have been linked to mental and physical health. This twin study reveals genetic influences on an individual’s orientation towards nature and nature experiences, opening a new dimension to understanding human-nature interactions.

PURPOSE To describe a small case series of infectious keratitis with poor visual outcomes after amniotic membrane (AM) placement and to prospectively evaluate whether AM demonstrates antibacterial activity in vitro against pathogens commonly isolated from infectious corneal ulcers. METHODS A retrospective case series and in vitro study of antibacterial activity of dehydrated AM using disk diffusion and measurement of inhibitory zones for bacterial assessment and inverted microscopy analysis for Acanthamoeba sp. growth. RESULTS Three cases of known etiology infectious keratitis are described where the clinical presentation worsened after treatment with AM. In vitro analysis of dehydrated AM, with and without a soft contact lens, demonstrated no inhibition of growth against Pseudomonas aeruginosa or Streptococcus pneumoniae. There was minimal growth inhibition of Staphylococcus aureus, although these zones of inhibition were much smaller than that surrounding the positive control. For Acanthamoeba sp., solubilized, dehydrated AM did not alter cyst density. CONCLUSIONS In an in vitro analysis, dehydrated AM did not provide evidence for a potentially clinically meaningful antibacterial effect against organisms commonly isolated from corneal ulcers.

Identification of novel and reliable biomarkers is crucial for the early detection and prognosis prediction of esophageal squamous cell carcinoma (ESCC). In this study, we aimed to explore the potential clinical significance of serum exosomal miR-182 in ESCC.A total of 125 patients with ESCC and 60 healthy volunteers were enrolled in this study. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect the serum exosomal miR-182 level. Then, the associations between serum exosomal miR-182 levels and clinicopathological features, as well as clinical outcome were further investigated.Serum exosomal miR-182 levels were significantly higher in pre-operative ESCC patients than in normal controls and post-operative ESCC patients. In addition, the receiver operating characteristic (ROC) curve analysis showed that the serum exosomal miR-182 could well differentiate ESCC patients from the healthy controls. Moreover, high serum exosomal miR-182 expression was strongly associated with worse clinical parameters including differentiation, lymph node metastasis, and TNM stage. ESCC patients in the high serum exosomal miR-182 group had significantly shorter overall survival and relapse free survival than those in the low serum exosomal miR-182 group. Furthermore, serum exosomal miR-182 was an independent prognostic indicator for ESCC.Collectively, serum exosomal miR-182 might serve as a promising biomarker for predicting the unfavorable prognosis of ESCC.

Purpose To determine whether increased growth differentiation factor 15 (GDF15) in aqueous humor (AH) is associated with worse visual field loss in patients with pseudoexfoliative glaucoma (PXG). Methods We recruited 12 patients (6 males, 6 females) with primary open-angle glaucoma (POAG) or PXG who were scheduled to undergo glaucoma surgery. AH was obtained from the initial peripheral paracentesis for the planned glaucoma surgery, and GDF15 levels were quantified with enzyme-linked immunosorbent assay by an investigator masked to clinical information. Humphrey visual field testing was performed as a part of routine care; results were obtained by reviewing the medical record. Results AH GDF15 was detectable in patients with POAG and PXG. Increased AH GDF15 was significantly associated with worse mean deviation in patients with POAG (r = -0.94; 95% confidence interval [CI], -0.99 to -0.33; P = 0.02) and PXG (r = -0.92; 95% CI, -0.99 to -0.41; P = 0.01). Conclusions AH GDF15 is detectable in patients with PXG and POAG. Elevated AH GDF15 is strongly associated with worse mean deviation in both subgroups. These findings suggest that GDF15 may be a molecular marker of glaucoma severity that is generalizable to multiple types of glaucoma regardless of the underlying etiology. Translational relevance This study provides proof of concept that GDF15, a molecular marker of retinal ganglion stress that was initially identified in rodent models, may have clinical utility as a measure of glaucoma severity not only in POAG but also in PXG.

INTRODUCTION Greater understanding of the impact of low intensity psychosocial interventions delivered by behavioral health clinicians (BHCs) working in an integrated care program (ICP) may promote better depression care. METHOD In a randomized controlled trial, 153 participants identified as depressed by their primary care provider (PCP) were assigned to ICP or usual care (UC, management by PCP, including specialty referral). In the ICP condition, BHCs worked collaboratively with PCPs and liaison psychiatrists. RESULTS ICP participants with lower and higher severity symptoms reported significantly greater use of coping strategies than UC participants at the 1-month follow up (lower: p = .002; higher: p = .016). ICP participants with lower severity continued to report significantly greater use of coping strategies than UC participants at the 4-month (p = .024), and 7-month (p = .012) follow ups. ICP participants were more likely to be following relapse preventions plans at the 4-month follow up (lower: 89.5% vs. 50%, p = .0.000; higher 74.1% vs. 33%, p = .0001). ICP participants also reported use of antidepressant medications on more days than UC participants at the 4-month follow up (lower: 21.27 vs. 14.49 days, p = .049; higher: 24.61 vs. 17.08 days, p = .035). Patient retention in the ICP was high, and ICP participants were significantly more satisfied with depression care than UC participants at follow-up assessments. DISCUSSION Delivery of low intensity psychosocial interventions by BHCs was associated with improvements to behavior charge targets. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

The mechanism underlying IOP elevation associated with intravitreal injections is unknown. Using anterior segment OCT, we found no significant differences in angle width associated with number of intravitreal injections that might explain this phenomenon.

Context Osteopathic manipulative treatment (OMT) and yoga are both recommended by systematic reviews in the evidence-based research literature for low back pain management. It is unknown, to the authors’ knowledge, what the effect of personal experience with OMT or yoga, reading research articles on OMT or yoga, or both will have on medical students’ recommendations for these treatment options to future patients with chronic low back pain. Objective To evaluate the likelihood of osteopathic medical students recommending OMT or yoga to treat patients with chronic low back pain based on their personal experience or reading research articles that recommend OMT or yoga for patients with chronic low back pain. Methods In this prospective cohort study, researchers administered an anonymous 18-question online survey for osteopathic medical students. The survey included a patient vignette, 2 evidence-based articles, and multiple choice, yes/no, and Likert-type questions. Participants were recruited via email from all 4 years of medical school. Between-group differences in proportions were assessed with descriptive statistics and χ2 tests; differences within groups were assessed with the McNemar test; and Fischer exact tests were used when expected cell counts were less than 5. Results A total of 180 participants (100 male, 80 female) completed the study. Personal experience increased the likelihood of osteopathic medical students recommending OMT (P<.018) or yoga (PPP Conclusion Personal experience and reading evidence-based research may increase the likelihood that osteopathic medical students will recommend OMT to future patients with chronic low back pain.

The effects of local body cooling on thermal comfort and sleep quality in a hot environment were investigated in an experiment with 16 male subjects. Sleep quality was evaluated subjectively, using questionnaires completed in the morning, and objectively, by analysis of electroencephalogram (EEG) signals that were continuously monitored during the sleeping period. Compared with no cooling, the largest improvement in thermal comfort and sleep quality was observed when the back and head (neck) were both cooled at a room temperature of 32°C. Back cooling alone also improved thermal comfort and sleep quality, although the effects were less than when cooling both back and head (neck). Mean sleep efficiency was improved from 84.6% in the no cooling condition to 95.3% and 92.8%, respectively, in these conditions, indicating good sleep quality. Head (neck) cooling alone slightly improved thermal comfort and subjective sleep quality and increased Stage N3 sleep, but did not otherwise improve sleep quality. The results show that local cooling applied to large body sections (back and head) could effectively maintain good sleep and improve thermal comfort in a hot environment.

Background:Risk factors associated with short-term functional outcomes in patients with operative ankle fractures have been established. However, no previous studies have reported the association between these risk factors and functional outcomes outside of the first postoperative year. We identified predictors of functional and pain outcomes in patients with operative ankle fractures using the Patient Reported Outcomes Measurement System (PROMIS) physical function (PF) and pain interference (PI) measures.Methods:We retrospectively reviewed a multicenter cohort of patients ≥18 years old who underwent operative management of closed ankle fractures from 2001 to 2013 with a minimum of a 2-year follow-up. Patients with pilon variants, Maisonneuve fractures, Charcot arthropathy, prior ankle surgery, and chronic ankle fractures were excluded. Patients meeting inclusion criteria were contacted and evaluated using the PROMIS PF and PI computerized adaptive tests. Patient demographic and injury characteristics were obtained through a retrospective chart review. Univariate and multivariate regression models were developed to determine independent predictors of physical function and pain at follow-up. Included in this study were 142 patients (64 women, 78 men) with a mean age of 52.7 years (SD = 14.7) averaging 6.3 years of follow-up (range 2-14).Results:Patients had a mean PF of 51.9 (SD = 10.0) and a mean PI of 47.8 (SD = 8.45). Multivariate analysis demonstrated that independent predictors of decreased PF included higher age (B = 0.16, P = .03), higher American Society of Anesthesiologists (ASA) class (B = 10.3, P < .01), and higher body mass index (BMI; B = 0.44, P < .01). Predictors of increased PI included higher ASA class (B = 11.5, P < .01) and lower BMI (B = 0.41, P < .01).Conclusion:At follow-up, increased ASA class, increased BMI, and higher age at time of surgery were independently predictive of decreased physical function. Factors that were associated with increased pain at follow-up include lower BMI and higher ASA class. ASA class had the strongest effect on both physical function and pain.Level of Evidence:Level IV, case series.

Prexasertib is a novel inhibitor of checkpoint kinase 1. The primary objective of this study was to evaluate prexasertib tolerability in Japanese patients with advanced solid tumors. This nonrandomized single-arm open-label phase 1 study of prexasertib consisted of 2 dose levels, 80 mg/m2 and the global-recommended dose based on a US study of 105 mg/m2 , administered intravenously once every 14 days (n = 6 for each dose). Transition to the higher dose proceeded if the frequency of dose-limiting toxicity observed in cycle 1 was

Background Blepharophimosis syndrome (BPES) is characterized by eyelid malformation with occasional premature ovarian failure. Mutations in FOXL2 underlie a fraction of BPES cases. Objective We aimed to investigate the genetic basis of BPES in 26 Chinese families that included 78 patients. Methods We performed ophthalmological examinations on each family member. We used Sanger sequencing to screen FOXL2 exons and their flanking sequences. We also performed bioinformatics studies, structural modeling and pathogenicity evaluations on all identified variations. Literature was reviewed and genotype-phenotype correlation analysis was performed. Results The patients had typical manifestations of BPES. Ten mutations were identified in ten of the twenty-six families. Among these, seven were novel mutations. These included the six truncating mutations, p.Glu69*, p.Gly256Glyfs*14, p.Ala14Serfs*135, p.Pro333Profs*200, p.Pro290Leufs*70, and p.Pro157Profs*91, and one missense mutation, p.Tyr59Cys. The mutations were scattered within the gene, and no mutational hotspots were found. Genotype-phenotype correlation analysis showed that frameshift or nonsense mutations were correlated with type I BPES, while in-frame or missense mutations were associated with type II BPES. Conclusion We report the largest BPES cohort in China thus far as well as seven novel mutations in FOXL2. The identification of novel mutations has not only expanded the mutational spectrum of the gene (which is valuable for mutation detection-based screening) but also suggests that most mutations within the Chinese population may not have been characterized yet.

Macrophage aging is pathogenic in diseases of the elderly, including age-related macular degeneration (AMD), a leading cause of blindness in older adults. However, the role of microRNAs, which modulate immune processes, in regulating macrophage dysfunction and thereby promoting age-associated diseases is underexplored. Here, we report that microRNA-150 (miR-150) coordinates transcriptomic changes in aged murine macrophages, especially those associated with aberrant lipid trafficking and metabolism in AMD pathogenesis. Molecular profiling confirmed that aged murine macrophages exhibit dysregulated ceramide and phospholipid profiles compared with young macrophages. Of translational relevance, upregulation of miR-150 in human peripheral blood mononuclear cells was also significantly associated with increased odds of AMD, even after controlling for age. Mechanistically, miR-150 directly targets stearoyl-CoA desaturase-2, which coordinates macrophage-mediated inflammation and pathologic angiogenesis, as seen in AMD, in a VEGF-independent manner. Together, our results implicate miR-150 as pathogenic in AMD and provide potentially novel molecular insights into diseases of aging.

To observe the curative effect and safety of one-third dose Verteporfin photodynamic therapy (PDT) in the treatment of chronic central serous chorioretinopathy (CSC).A total of 60 patients (68 eyes) treated in our hospital from January 2016 to December 2016 were selected in this study, and they were diagnosed with chronic CSC via fluorescein fundus angiography (FFA), indocyanine green angiography (ICGA) and optical coherence tomography (OCT). Besides, patients were treated with one-third conventional dose Verteporfin PDT. The subfoveal choroidal thickness (SFCT), superior, inferior, nasal and temporal choroidal thickness at 1.5 mm away from macula central fovea, central choroidal capillary layer thickness, photoreceptor layer thickness, best corrected visual acuity (BCVA), subretinal fluid absorption, FFA and ICGA manifestations and complications of patients were observed and recorded before treatment and at 1, 3 and 6 months after treatment.After PDT via one-third conventional dose of Verteporfin, patients were followed up for 1 month, 3 months, and 6 months. The SFCT of affected eyes was changed from (381.23 ± 83.29) μm before treatment to (385.31 ± 90.89) μm, (369.59 ± 75.60) μm and (374.08 ± 102.81) μm successively, and the differences were statistically significant (p0.001). Central choroidal capillary layer thickness and superior, inferior, nasal and temporal choroidal thickness at 1.5 mm away from macula central fovea (SCT1.5mm, ICT1.5mm, NCT1.5mm and TCT1.5mm) were significantly decreased at 1 month, 3 months and 6 months after treatment compared with those before treatment (p0.001). With the passage of time after treatment, the photoreceptor layer thickness of affected eyes was increased gradually, and the difference was statistically significant (F = 268.8, p0.0001). After PDT, BCVA had a statistically significant difference compared with that before treatment (p = 36.16, p0.001); BCVA at 3 months after treatment had no statistically significant difference compared with that at 6 months after treatment (p0.05). At 6 months after treatment, the subretinal fluid in 63 eyes (92.6%) completely subsided, and a little subretinal fluid was retained in 5 eyes (7.4%). FFA and ICGA showed the choroidal vessel dilatation in affected eyes after treatment and significantly improved moderate-advanced high fluorescein leakage compared with that before treatment. There were no obvious complications in the body and fundus during the follow-up period.One-third dose Verteporfin PDT can improve BCVA, stop or reduce the choroidal vasodilatation and leakage, accelerate the absorption of serous subretinal fluid, and help the recovery of photoreceptor layer of patients with chronic CSC, which is safe and reliable.

Signal transducer and activator of transcription 3(STAT3) is an emerging target for cancer therapy. In this study, we identify Toosendanin (TSN) is an effective inhibitor of STAT3, leading to the impediment of various oncogenic processes in osteosarcoma. TSN selectively inactivates phospho-STAT3 (Tyr-705); subsequent molecular docking and in vitro SPR analysis uncover TSN directly binds to the SH2 domain of STAT3. Consequently, TSN blocks STAT3 dimerization and impairs the complex formation of STAT3 and epidermal growth factor receptor (EGFR). In an animal tumor model study, TSN is well tolerated, inhibits osteosarcoma growth and metastasis. In another osteosarcoma patient-derived xenografts (PDX) model, we find TSN triggers strong inhibitory effects on patient-derived tumors. Further studies show that TSN also displays activity against other solid tumors. Our preclinical work therefore supports that TSN acts as a novel inhibitor of STAT3 that blocks tumorigenesis in ostoesarcoma.

CUB-domain-containing protein 1 (CDCP1) is a trans-membrane protein regulator of cell adhesion with a potent pro-migratory function in tumors. Given that proteolytic cleavage of the ectodomain correlates with outside-in oncogenic signaling, we characterized glycosylation in the context of cellular processing and expression of CDCP1 in prostate cancer. We detected 135 kDa full-length and proteolytic processed 70 kDa species in a panel of PCa cell models. The relative expression of full-length CDCP1 correlated with the metastatic potential of syngeneic cell models and an increase in surface membrane expression of CDCP1 was observed in tumor compared to adjacent normal prostate tissues. We demonstrated that glycosylation of CDCP1 is a prerequisite for protein stability and plasma membrane localization, and that the expression level and extent of N-glycosylation of CDCP1 correlated with metastatic status. Interestingly, complex N-linked glycans with sialic acid chains were restricted to the N-terminal half of the ectodomain and absent in the truncated species. Characterization of the extracellular expression of CDCP1 identified novel circulating forms and revealed that extracellular vesicles provide additional processing pathways. Employing immunoaffinity mass spectrometry, we detected elevated levels of circulating CDCP1 in patient urine with high-risk disease. Our results establish that differential glycosylation, cell surface presentation and extracellular expression of CDCP1 are hallmarks of PCa progression.

Purpose The purpose of this study was to determine whether subjects who wear short wavelength-blocking eyeglasses during computer tasks exhibit less visual fatigue and report fewer symptoms of visual discomfort than subjects wearing eyeglasses with clear lenses. Methods A total of 36 healthy subjects (20 male; 16 female) was randomized to wearing no-block, low-blocking, or high-blocking eyeglasses while performing a 2-hour computer task. A masked grader measured critical flicker fusion frequency (CFF) as a metric of eye fatigue and evaluated symptoms of eye strain with a 15-item questionnaire before and after computer use. Results We found that the change in CFF after the computer task was significantly more positive (i.e., less eye fatigue) in the high-block versus the no-block (P = 0.027) and low-block (P = 0.008) groups. Moreover, random assignment to the high-block group but not to the low-block group predicted a more positive change in CFF (i.e., less eye fatigue) following the computer task (adjusted β = 2.310; P = 0.002). Additionally, subjects wearing high-blocking eyeglasses reported significantly less feeling pain around/inside the eye (P = 0.0063), less feeling that the eyes were heavy (P = 0.0189), and less feeling that the eyes were itchy (P = 0.0043) following the computer task, when compared to subjects not wearing high-blocking lenses. Conclusions Our results support the hypothesis that short-wavelength light-blocking eyeglasses may reduce eye strain associated with computer use based on a physiologic correlate of eye fatigue and on subjects' reporting of symptoms typically associated with eye strain.

Purpose Fingernail-induced corneal abrasions are one of the most common eye injuries that present to the emergency department, and yet there is little literature available to offer guidelines for management. We analyzed the treatment used in cases of fingernail-induced corneal abrasions that presented to the Massachusetts Eye and Ear Infirmary Emergency Department and studied its relationship to the development of complications such as recurrent erosion syndrome and infection. Methods We performed a retrospective review of 99 patients who presented to the Massachusetts Eye and Ear Infirmary Emergency Department with fingernail-induced corneal abrasions between January 1, 2009 and December 31, 2009. We followed the patients for 12 months and documented demographics, nature of the injury, treatment, and complications. Results The average age was 29.4 (range, 2-89) years. Forty-four percent (n = 44) were female and 56% (n = 55) were male. Of the 99 subjects, 39 had a full 12 month follow-up, and 7 developed a complication from the injury. Compared with the 32 subjects without complications, there was no difference in age or gender. However, there was a significant difference in that adults scratched by another adult were more highly represented in the group with complications (43%, n = 3/7 vs. 3%, n = 1/32; P = 0.0017). There was no significant difference in outcome by treatment used. Conclusions This is the largest fingernail-induced corneal abrasion study completed to date. Patients are at risk of developing complications, but there is scant evidenced-based literature available for treating this common injury. Prospective trials should be performed to better optimize and standardize treatments.

Purpose The purpose of the study was to compare behavioral outcomes (physical activity, sedentary behavior, smoking cessation, diet) between the intervention and usual care conditions from the TEAMcare trial. Methods TEAMcare was a randomized trial among 214 adults with depression and poorly controlled diabetes and/or coronary heart disease that promoted health behavior change and pharmacotherapy to improve health. Behavioral outcomes were measured with the International Physical Activity Questionnaire (physical activity, sitting time) and the Summary of Diabetes Self-Care Activities Measure (smoking, diet, exercise). Poisson regression models among completers ( N =185) were conducted adjusting for age, education, smoking status and depression. Results Intervention participants had more days/week following a healthy eating plan [relative rate=1.2, 95% confidence interval (CI)=1.1–1.4] and more days of participation in 30 min of physical activity (relative rate=1.2, 95% CI=1.1–2.0) compared to usual care. Intervention participants were more likely to meet physical activity guidelines (7.5% increase) compared to usual care (12% decrease; P =.053). Conclusion Diet and activity generally improved for those receiving the intervention, while there were no differences in some aspects of diet (fruit and vegetable and high-fat food intake), smoking status and sitting time between conditions in the TEAMcare trial.

Correlates of patient disclosure of suicide ideation to a primary care or mental health provider were identified. Secondary analyses of IMPACT trial data were conducted. Of the 107 patients 60 years of age or older who endorsed thoughts of ending their life at least "a little bit" during the past month, 53 indicated they had disclosed these thoughts to a mental health or primary care provider during this period. Multiple logistic regression was used to identify predictors of disclosure to a provider. Significant predictors included poorer quality of life and prior mental health specialty treatment. Among participants endorsing thoughts of suicide, the likelihood of disclosing these thoughts to a provider was 2.96 times higher if they had a prior history of mental health specialty treatment and 1.56 times higher for every one-unit decrease in quality of life. Variation in disclosure of thoughts of suicide to a mental health or primary care provider depends, in part, on patient characteristics. Although the provision of evidence-based suicide risk assessment and guidelines could minimize unwanted variation and enhance disclosure, efforts to routinize the process of suicide risk assessment should also consider effective ways to lessen potential unintended consequences.

Aging is a significant risk factor for impaired tissue functions and chronic diseases. Age-associated decline in systemic NAD(+) availability plays a critical role in regulating the aging process across many species. Here we show that the circulating levels of extracellular nicotinamide phosphoribosyltransferase (eNAMPT) significantly decline with age in mice and humans. Increasing circulating eNAMPT levels in aged mice by adipose-tissue specific overexpression of NAMPT increases NAD(+) levels in multiple tissues, thereby enhancing their functions and extending healthspan in female mice. Interestingly, eNAMPT is carried in extracellular vesicles (EVs) through systemic circulation in mice and humans. EV-contained eNAMPT is internalized into cells and enhances NAD(+) biosynthesis. Supplementing eNAMPT-containing EVs isolated from young mice significantly improves wheel-running activity and extends lifespan in aged mice. Our findings have revealed a novel EV-mediated delivery mechanism for eNAMPT, which promotes systemic NAD(+) biosynthesis and counteracts aging, suggesting a potential avenue for anti-aging intervention in humans.

Background When depression co-occurs with type 2 diabetes, adverse bidirectional interactions increase the burden of both illnesses. In addition to affecting patient's health, functioning, and quality of life, this relationship also results in increased mortality compared with those with depression or diabetes alone. Objective The purpose of this study was to examine the relationship between depression and all-cause as well as cause-specific mortality in patients with type 2 diabetes by extending findings from our 5-year mortality study. Specifically, we re-examined the risk of depression and all-cause, cardiovascular, cancer, and non-cardiovascular, non-cancer related deaths. Method We used an ICD-10 algorithm combined with death certificate data to classify mortality types among type 2 diabetic patients who participated in the Pathways Epidemiologic Study. Cox proportional hazard modeling was used to examine the relationships between depression status and mortality over a 10-year period. Results We found a significant positive relationship between depression and all-cause as well as non-cardiovascular, non-cancer mortality in this sample (n = 4128). Cardiovascular mortality failed to reach significance in fully adjusted models and, in contrast to the 5-year data, no trend or significant relationship was observed between depression status and cancer related deaths. Conclusions Our study confirmed a significant positive relationship between depression and mortality in patients with type 2 diabetes. Major depression demonstrated a stronger relationship than did minor depression, and among cause-specific groups, non-cardiovascular, non-cancer death types demonstrated the largest magnitude of association with depression status.

Objective Demonstrate the feasibility of implementing a collaborative care program for poorly-controlled type 2 diabetes and complex behavioral health disorders in an urban academically-affiliated safety net primary care clinic. Methods This retrospective cohort study evaluates multidisciplinary team care approach to diabetes in a safety net clinic, and included 634 primary care clinic patients with hemoglobin A1c (HbA1c) > 9%. HbA1c, blood pressure, and depression severity were assessed at the initial visit and at the end of treatment, and compared to those of patients who were not referred to the team. Results The 151 patients referred to the program between March 2013 and November 2014 had a higher initial mean HbA1c: 10.6% vs. 9.4%, and were more likely to have depression (p = 0.006), anxiety (p = 0.04), and bipolar disorder (p = 0.03), compared to the 483 patients who were not referred. During the 18-month study period, there was a mean decrease in HbA1c of 0.9 (10.6 to 9.4) among those referred to the team, compared to a mean decrease of 0.2 (9.4 to 9.2) among those not referred. This was a significantly greater percent change in HbA1c (p = 0.008). Conclusion The integration of behavioral healthcare into chronic care management of patients with diabetes is a promising strategy to improve outcomes among the high risk population in safety net settings.

Nature within cities will have a central role in helping address key global public health challenges associated with urbanization. However, there is almost no guidance on how much or how frequently people need to engage with nature, and what types or characteristics of nature need to be incorporated in cities for the best health outcomes. Here we use a nature dose framework to examine the associations between the duration, frequency and intensity of exposure to nature and health in an urban population. We show that people who made long visits to green spaces had lower rates of depression and high blood pressure, and those who visited more frequently had greater social cohesion. Higher levels of physical activity were linked to both duration and frequency of green space visits. A dose-response analysis for depression and high blood pressure suggest that visits to outdoor green spaces of 30 minutes or more during the course of a week could reduce the population prevalence of these illnesses by up to 7% and 9% respectively. Given that the societal costs of depression alone in Australia are estimated at AUD$12.6 billion per annum, savings to public health budgets across all health outcomes could be immense.

To assess the effectiveness and safety of the conversion therapy from traditional cyclosporine (CsA) triple immunosuppression therapy to sirolimus (SRL) combined with low dose CsA and prednisone (Pred) in renal transplantation recipients in a five-year follow-up period.A prospective, open-label non-randomized study was performed with 46 renal allograft recipients who visited Tongji Hospital regularly for follow-up visits between January 2007 and May 2011 and were taking CsA+ mycophenolate mofetil (MMF)+ Pred. Conversion therapy to SRL+ low dose CsA+ Pred was initiated after renal transplantation. The recipients were allocated to 2 groups according to their renal function and proteinuria before the conversion: active conversion group [n=27, serum creatinine (SCr) ≤ 140 μmol/L with no or minimal proteinuria] and passive conversion group [n=19, SCr140 μmol/L with less than moderate proteinuria]. After conversion, dosages of SRL and CsA were adjusted for trough levels of 5-7 μg/L and 20-60 μg/L, respectively. SCr and urine protein were compared before and after the conversion in five-year follow-up. Incidence of acute rejection, renal graft survival and SRL-related adverse effects of the immunosuppressive regimen were also observed.After conversion, an average 63% dose reduction of CsA was achieved in all the patients. In the active conversion group, the mean SCr level was (110±19) μmol/L at the time of conversion. Eight patients in this group withdrew from the study during the follow-up period for the following reasons: arthralgia (1 case), deteriorated proteinuria (2 cases), chronic diarrhea (2 cases), mild or suspicious acute rejection (2 cases), and recurrent fever (1 case). The rest patients (19/27) with a mean follow-up time of 5 years had a stable SCr level [(103±12) μmol/L] and a 100% 5-year graft survival. In the passive conversion group, the mean SCr level was (205±45) μmol/L at the time of conversion. There were 4 patients quitting the study, 2 for deteriorated proteinuria and 2 for lost to follow-up. Chronic allograft failure developed in 10 patients in this group 1-50 months after conversion, while the remaining 5 patients had a stable SCr during the 5-year follow-up period [(218 ±46) μmol/L before conversion vs (205±73) μmol/L 5 years after conversion]. The overall 5-year graft survival after the conversion therapy in the passive conversion group was 33.3%, significantly lower than that of the active conversion group (P0.001). Acute rejection was observed in 2 cases in the active conversion group, while not observed in the passive conversion group. None of the patients developed leukopenia, thrombocytopenia, oral ulcer, or pneumonia in the follow-up.The combination therapy of SRL and low dose of CsA is overall a safe and effective maintenance immunosuppressive regimen, but it is important to initiate at an appropriate stage. More favourable long-term benefits may be obtained from the conversion therapy in patients with normal or only slightly impaired renal graft function. It may offer an option of individualized immunosuppressive therapy after renal transplantation.

Background Nasal polyposis (NP) is a Th2-skewed inflammatory disorder, but it is unclear what role regulatory T cells (T-reg) play in disease pathology. We investigated the expression profiles of T-reg and T-helper-cell-associated genes and their response to glucocorticosteroid (GC) treatment in Chinese patients with NP. Methods Biopsies were obtained from 29 non-treated NP patients for comparison with inferior turbinates collected from healthy controls. In 13 patients, NP samples were collected both before and after short-term oral GC treatment. Levels of mRNA for T-cell markers were determined by microarray and quantitative PCR. Cellular infiltrates were assessed by histo- and immunohistochemistry. Results FOXP3+ T-reg were increased in GC-naive NP, and numbers were negatively correlated with eosinophil infiltration. Helios staining was not detected, suggesting that FOXP3+ cells in NP are not thymus-derived T-reg. Compared with controls, mRNA levels corresponding to T-reg genes were significantly increased in NP (FOXP3, TGFB1, IL10, SMAD3, IL2RA, and JAK3), but transcription factors associated with Th2 (GATA3) or Th17 responses (RORc) were significantly reduced. FOXP3 mRNA levels positively correlated with other T-reg cell markers. Microarray analysis showed that most Th2-related markers (e.g., Eotaxin-1, CCL13, and CCL18) were upregulated in GC-naive NP vs controls. GC therapy significantly suppressed eosinophilic inflammation in NP, but did not significantly alter the expression levels of T-reg/Th2-associated genes. Conclusions Upregulation of FOXP3+-inducible T-reg cells and downregulation of Th2 and Th17 markers in NP indicate a regulatory response occurring at a site of persistent mucosal inflammation. However, immune regulation fails to control the underlying tissue pathology. Expression of T-reg/Th2 markers after GC treatment was unaltered, suggesting that T-cell-driving NP inflammatory mediators are GC resistant.

Objective To examine the association between changes in depressive symptoms and disability status in patients with diabetes. Methods This 5-year prospective cohort study included 2733 patients with diabetes enrolled in the Pathways Epidemiologic Follow-Up Study who had completed depression and activities of daily living questionnaires at baseline and 5 years. Four depression groups were created using changes in depression scores over 5 years: no depression, improved depression, persistent depression, and development of depression. After controlling for sociodemographic and clinical characteristics, we examined the association between changes in depressive symptoms and incident disability at 5 years using Poisson regression. Results In patients nondisabled at baseline (n = 2155), the improved depression group had a risk of disability comparable to the no depression reference group [relative risk (RR): 0.70, 95% CI (0.44–1.12)]. The development of depression and persistent depression groups were significantly more likely to develop disability compared with the no depression group [RR: 2.86, 95% CI (2.12–3.86) and RR: 2.16, 95% CI (1.47–3.18), respectively]. Among those who were disabled at baseline, there was no significant change in the disability status of the three depression groups compared with disabled patients with no depressive symptoms at either time point. Conclusions Among initially nondisabled patients with diabetes, those whose depression improved had functional outcomes comparable to those who were nondepressed at baseline and 5 years. Patients who developed depression and had persistent depression were more likely to experience disability at 5 years than those who were nondepressed at baseline and 5 years.

PURPOSE Medication nonadherence, inconsistent patient self-monitoring, and inadequate treatment adjustment exacerbate poor disease control. In a collaborative, team-based, care management program for complex patients (TEAMcare), we assessed patient and physician behaviors (medication adherence, self-monitoring, and treatment adjustment) in achieving better outcomes for diabetes, coronary heart disease, and depression. METHODS A randomized controlled trial was conducted (2007-2009) in 14 primary care clinics among 214 patients with poorly controlled diabetes (glycated hemoglobin [HbA1c] ≥8.5%) or coronary heart disease (blood pressure >140/90 mm Hg or low-density lipoprotein cholesterol >130 mg/dL) with coexisting depression (Patient Health Questionnaire-9 score ≥10). In the TEAMcare program, a nurse care manager collaborated closely with primary care physicians, patients, and consultants to deliver a treat-to-target approach across multiple conditions. Measures included medication initiation, adjustment, adherence, and disease self-monitoring. RESULTS Pharmacotherapy initiation and adjustment rates were sixfold higher for antidepressants (relative rate [RR] = 6.20; P

Objective This study examined whether depression is associated with a higher incidence of diabetic retinopathy among adults with type 2 diabetes after controlling for sociodemographic factors, health risk behaviors and clinical characteristics. Method This study included 2359 patients enrolled in Pathways Epidemiologic Follow-Up Study, a prospective cohort study investigating the impact of depression in primary care patients with type 2 diabetes. The predictor of interest was baseline severity of depressive symptoms assessed with the Patient Health Questionnaire-9 (PHQ-9). The outcome was incident diabetic retinopathy. Risk of diabetic retinopathy was assessed using logistic regression, and time to incident diabetic retinopathy was examined using Cox proportional hazard models. Results Over a 5-year follow-up period, severity of depression was associated with an increased risk of incident retinopathy [odds ratio=1.026; 95% confidence interval (CI) 1.002–1.051] as well as time to incident retinopathy (hazard ratio=1.025; 95% CI 1.009–1.041). The risk of incident diabetic retinopathy was estimated to increase by up to 15% for every significant increase in depressive symptoms severity (5-point increase on the PHQ-9 score). Conclusion Diabetic patients with comorbid depression have a significantly higher risk of developing diabetic retinopathy. Improving depression treatment in patients with diabetes could contribute to diabetic retinopathy prevention.

Patients with poorly controlled diabetes, coronary heart disease, and depression have an increased risk of adverse outcomes. In a randomized, controlled trial, we tested an intervention designed to improve disease control outcomes for diabetes and/or heart disease and coexisting depression. Patients with one or more parameters of poor medical disease control (ie, HbA1c ≥8.5, or SBP >140, or LDL >130) and a Patient Health Questionnaire-9 (PHQ-9) ≥10 were randomized to the TEAMcare intervention or usual care (N = 214). This article will describe the TEAMcare health services model that has been shown to improve quality of care and medical and psychiatric outcomes.

Visual imagery comprises object and spatial dimensions. Both types of imagery encode shape but a key difference is that object imagers are more likely to encode surface properties than spatial imagers. Since visual and haptic object representations share many characteristics, we investigated whether haptic and multisensory representations also share an object-spatial continuum. Experiment 1 involved two tasks in both visual and haptic within-modal conditions, one requiring discrimination of shape across changes in texture, the other discrimination of texture across changes in shape. In both modalities, spatial imagers could ignore changes in texture but not shape, whereas object imagers could ignore changes in shape but not texture. Experiment 2 re-analyzed a cross-modal version of the shape discrimination task from an earlier study. We found that spatial imagers could discriminate shape across changes in texture but object imagers could not; and that the more one preferred object imagery, the more texture changes impaired discrimination. These findings are the first evidence that object and spatial dimensions of imagery can be observed in haptic and multisensory representations.