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NTRK-rearranged mesenchymal neoplasms mostly affect the soft tissues of pediatric patients. Given the responsiveness to selective NTRK inhibitors, it remains critical to identify those ultra-rare cases occurring in the viscera of adults. In five females and two males aged 18-53 years, we characterized visceral mesenchymal tumors harboring TPM3-NTRK1 [uterine cervix (N = 2), pleura, prostate], LMNA-NTRK1 (lung), SQSTM1-NTRK3 (heart), and NTRK3 rearrangement with unknown fusion partner (colon/mesocolon) with RNA sequencing, FISH, RT-PCR, and immunohistochemistry. The tumors exhibited spindled to ovoid/epithelioid or pleomorphic cells, often arranged in fascicles, and were low-to-intermediate-grade and high-grade in three and four cases, respectively. Keloid-like stromal collagen and perivascular hyalinization was noted in five. Adenosarcoma-like appearances were observed in two, manifesting frond-like protrusions in one cervical tumor and phyllodes-like architecture in the prostatic tumor. Abrupt high-grade transformation into pleomorphic liposarcoma was found in another cervical tumor, while the pleural tumor contained intermixed rhabdomyoblasts. Pan-TRK immunostaining was positive in all cases. All cases expressed CD34, while five were S100-positive. CDKN2A homozygous deletion with concomitant p16 loss occurred in 4/7. Whole-exome sequencing identified TP53 mutation (c.672+2TC, involving a splice site, with concomitant protein loss) in a cervical sarcoma, limited to its heterologous liposarcomatous component. At least moderate pan-TRK immunoreactivity was present in varying proportions of potential pathologic mimics, with BCOR-positive sarcoma (56%, 5/9), undifferentiated uterine sarcoma (50%, 3/6), and spindle cell/sclerosing rhabdomyosarcoma (33%, 2/6) being among the most frequent. This underscored the unsatisfactory specificity of pan-TRK immunohistochemistry and warranted molecular confirmation in the diagnosis of adult NTRK-rearranged visceral mesenchymal neoplasms. The current report highlights the ever-expanding clinicopathologic and genetic spectrum of this entity by describing the unprecedented cardiac and pleural locations and heterologous differentiation, as well as the second NTRK-rearranged "prostatic stromal sarcoma," while substantiating CDKN2A deletion as a frequent occurrence.

The aim of this study was to determine whether self-reported burn pit exposure is associated with increased subjective and objective sinus disease.A cross-sectional study was performed evaluating consecutive adult patients presenting to a US Military rhinology clinic. Demographics, medical histories, sinonasal quality-of-life scores, and nasal endoscopy examinations were obtained. Participants were divided into three cohorts based on self-reported exposure histories and outcomes compared.One hundred eighty-six patients met the inclusion criteria, the majority of whom were male. Patients with burn pit exposure had worse Sinonasal Outcome Test-22 scores (49.9) compared with those deployed without burn pit exposure (31.8) or never deployed (31.5). Endoscopic findings demonstrated worse disease within those exposed (Lund-Kennedy score, 3.3) compared with the other cohorts (1.8 and 1.7, respectively).These novel findings suggest that deployment-related burn pit exposure is associated with increased subjective and objective sinus disease.

This multicenter cohort study investigated the association of serology and comorbid conditions with septic and aseptic nonunion.From January 1, 2011, to December 31, 2017, consecutive individuals surgically treated for nonunion were identified from seven centers. Nonunion-type, comorbid conditions and serology were assessed.A total of 640 individuals were included. 57% were male with a mean age of 49 years. Nonunion sites included tibia (35.2%), femur (25.6%), humerus (20.3%), and other less frequent bones (18.9%). The type of nonunion included septic (17.7%) and aseptic (82.3%). Within aseptic, nonvascular (86.5%) and vascular (13.5%) nonunion were seen. Rates of smoking, alcohol abuse, and diabetes mellitus were higher in our nonunion cohort compared with population norms. Coronary artery disease and tobacco use were associated with septic nonunion (P0.05). Diphosphonates were associated with vascular nonunion (P0.05). Serologically, increased erythrocyte sedimentation rate, C-reactive protein, parathyroid hormone, red cell distribution width, mean platelet volume (MPV), and platelets and decreased absolute lymphocyte count, hemoglobin, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and albumin were associated with septic nonunion while lower calcium was associated with nonvascular nonunion (P0.05). The presence of four or more of increased erythrocyte sedimentation rate, C-reactive protein, or red cell distribution width; decreased albumin; and age younger than 65 years carried an 89% positive predictive value for infection. Hypovitaminosis D was seen less frequently than reported in the general population, whereas anemia was more common. However, aside from hematologic and inflammatory indices, no other serology was abnormal more than 25% of the time.Abnormal serology and comorbid conditions, including smoking, alcohol abuse, and diabetes mellitus, are seen in nonunion; however, serologic abnormalities may be less common than previously thought. Septic nonunion is associated with inflammation, younger age, and malnourishment. Based on the observed frequency of abnormality, routine laboratory work is not recommended for nonunion assessment; however, specific focused serology may help determine the presence of septic nonunion.

Introduction Orthodontic residents face challenges unparalleled to their predecessors, including competitive marketplaces, rising debt burdens, and changing demographics that have contributed to the shift in initial career choice from owner to employee. We aim to understand factors important to orthodontists at different career stages and the impact on job satisfaction through a sequential mixed methodology study. Methods Semistructured interviews were conducted with 25 orthodontic residents and practitioners. A survey was developed from qualitative findings that explored career decision-making of orthodontic residents and practicing orthodontists, with descriptive and bivariate statistical analyses (n = 343 orthodontists and 185 residents). Results Graduating orthodontic residents are choosing employment over ownership as their initial job, prioritizing high income to offset the educational debt. The majority of residents report thinking about their debt very often to all of the time and find it very to extremely stressful. Current residents have long-term goals of ownership, whereas practicing doctors of both genders became owners at equal frequencies. However, on average, women earn $119,000 less per year and report being the primary family caretaker more often than men. Conclusions Excellent patient care, work-life balance, and sufficient income are the most important drivers for career choices and job satisfaction for orthodontists of all ages. Despite debt, most residents and working orthodontists report a high level of job satisfaction and would recommend the field of orthodontics to others.

The increasing use of biologics is accompanied by a risk of hepatitis B (HBV) and C virus (HCV) reactivation.To determine the predictors of HBV and HCV reactivation in patients with psoriasis receiving biologics.This study screened 2060 patients with psoriasis (3562 treatment episodes) who were taking biologics from 2009 to 2018. There were 359 patients with psoriasis with HBV (561 treatment episodes) and 61 with HCV infection (112 treatment episodes).During 8809 and 1522 person-months of follow-up, 88 treatment episodes for HBV involved HBV reactivation, and 14 episodes of HCV involved reactivation. The reactivation rate was significantly higher in treatment episodes of chronic HBV infection than in that of occult HBV (34.3% vs 3.2%, P = .001) and resolved HBV (34.3% vs 5.0%, P .001). The multivariate analysis revealed that being hepatitis B surface antigen seropositive, being hepatitis B e-antigen seropositive, and tumor necrosis factor-α-inhibitor therapy were risk factors for HBV reactivation, whereas antiviral prophylaxis was effective in reducing the risk of HBV reactivation. No predictors were significantly associated with HCV reactivation.Observational design and a lack of a comparison group.Patients with psoriasis on biologics have a risk of HBV and HCV reactivations, particularly those who are seropositive for hepatitis B surface antigen and hepatitis B e-antigen and undergoing tumor necrosis factor-α-inhibitor therapy.

Although widely used in clinical practice, vertebral augmentation procedure (VAP) for osteoporotic vertebral compression fracture (OVCF) is not supported. Recently, the effect of recombinant human parathyroid hormone (1-34) (rhPTH) has been paid great attention for its efficacy in anti-osteoporosis and bone union. This study aims to explore the outcome of rhPTH on acute OVCF and compare it with VAP to clarify its therapeutic advantages.The retrospective study comprised 71 acute OVCF patients from January 2015 to March 2020: 22 received rhPTH treatment (rhPTH group) and 49 underwent VAP (VAP group). The rhPTH group was 15 women and seven men with an average of 76.18 years, and the VAP group were 35 women and 14 men with an average of 73.63 years. The thoracic/lumbar vertebrae were 14/8 in the rhPTH group and 29/20 in the VAP group. The average follow-up period was 14.05 months in the rhPTH group and 13.82 months in the VAP group. The two groups were assessed regarding the visual analog score (VAS), Oswestry Disability Index (ODI), OVCF bone union, bone mineral density (BMD), kyphotic angle (KA), anterior and posterior border height (ABH and PBH, respectively), adverse events and the health-related quality of life assessed by short form-36 health survey scores (SF-36). Categorical variables were analyzed by chi-square test and continuous variables between groups were analyzed by independent samples t-test or Mann-Whitney U test according to the normality.During the follow-up, the VAS was significantly lower in the rhPTH group than in the VAP group at month 3 (0.39 ± 0.6 vs 0.68 ± 0.651) (p = 0.047), month 6 (0.45 ± 0.60 vs 2.18 ± 1.22) (p 0.001), and month 12 (0.45 ± 0.60 vs 2.43 ± 1.49) (p 0.001). At month 12, the ODI was significantly lower in the rhPTH group (18.59 ± 3.33%) than in the VAP group (28.93 ± 16.71%) (p 0.001). Bone bridge was detected on sagittal computed tomography images of all fractured vertebrae in the rhPTH group. The BMD was significantly higher in the rhPTH group (87.66 ± 5.91 Hounsfield units [HU]) than in the VAP group (68.15 ± 11.32HU) (p 0.001). There were no significant differences in the changes in KA, ABH, and PBH between groups (all p 0.05). The incidence of new OVCF was significantly lower in the rhPTH group than in the VAP group (p = 0.042). All scores of SF-36 were significantly higher in the rhPTH group than in the VAP group (all p 0.05).In acute OVCF patients, rhPTH was better than VAP in increasing spinal BMD to promote OVCF healing, reduce new OVCF, and improve back pain, physical ability, and health-related quality of life.

The American Society of Hematology and American College of Chest Physicians heparin-induced thrombocytopenia guidelines recommend calculation of a pretest probability score prior to performing laboratory testing, and the 4Ts score is commonly used. Inter-rater agreement of the 4Ts score has been evaluated, but limited data are available regarding the reliability of the 4Ts score when performed by nonexpert clinicians. The purpose of this study was to Compare 4Ts scores calculated by medical teams to an expert. A single-center observational study was conducted in patients evaluated for heparin-induced thrombocytopenia over 24 months. The primary outcome was difference in mean 4Ts score calculated by the medical team compared with an expert. Secondary outcomes included inter-rater agreement in risk category assignment and the negative predictive value (NPV) of the 4Ts score. The mean total 4Ts score was significantly higher when calculated by the medical team compared with expert (4.16 ± 1.41 versus 3.42 ± 1.53; P < 0.001). There was slight agreement in risk category assignment (Cohen κ coefficient = 0.164; P = 0.005). The NPV of the 4Ts score was 0.949 (95% confidence interval 0.891-1.000) when calculated by the medical team and 0.927 (95% confidence interval 0.869-0.984) when calculated by expert. Total 4Ts scores calculated by the medical team were significantly higher with only slight inter-rater agreement compared with expert. The NPV of the 4Ts score when calculated by nonexperts may be lower than previously reported. The recommendation to forgo laboratory testing for low 4Ts score patients may need to be revisited.

Objective To compare the preventive effects of teriparatide and alendronate on the progression of vertebral body collapse in postmenopausal single‐level Kümmell's disease (KD). Methods From March 2013 to December 2020, the medical records for 53 postmenopausal single‐level KD patients who received conservative treatment with teriparatide (25 patients, teriparatide group) or alendronate (28 patients, alendronate group) were retrospectively reviewed. Midsagittal computed tomography (CT) images were analyzed by ImageJ to assess the intravertebral bone formation (mineralized bone) by calculating the ratio of area of intravertebral mineralized bone (AIMB) to the area of fractured vertebral body (AFVB). The changes in radiological parameters of the fractured vertebral body including kyphosis angle (KA), anterior and posterior border heights (ABH and PBH) and spinal canal diameter (SCD), bone turnover biomarkers (BTMs), and bone mineral density (BMD) were analyzed to evaluate the therapeutic effect. Results At month 12, the ratio of AIMB to AFVB was significantly greater in teriparatide group (54.28% ± 15.30%) than in alendronate group (35.57% ± 17.61%) (P, Illustrating the KD diagnosis. The hyperintensity detected on sagittal T2‐weighted MR images (A) and fat‐suppressed sequence (B) within T12 for an 84‐year‐old patient or the gas‐containing cleft detected on the CT scan (C) with T10 for a 69‐year‐old patient demonstrates the formation of intravertebral vacuum cleft (arrows), indicating KD. KD Kümmell's disease.

CONTEXT. Cancer prognosis data often come from clinical trials which exclude patients with acute illness. OBJECTIVES. For patients with Stage IV cancer and acute illness hospitalization to 1) describe predictors of 60-day mortality and 2) compare documented decision-making for survivors and decedents. METHODS. Investigators studied a consecutive prospective cohort of patients with Stage IV cancer and acute illness hospitalization. Structured health record and obituary reviews provided data on 60-day mortality (outcome), demographics, health status, and treatment; logistic regression models identified mortality predictors. RESULTS. Four hundred ninety-two patients with Stage IV cancer and acute illness hospitalization had median age of 60.2 (51% female, 38% minority race/ethnicity); 156 (32%) died within 60 days, and median survival for decedents was 28 days. Nutritional insufficiency (odds rato [OR] 1.83), serum albumin (OR 2.15 per 1.0 g/dL), and hospital days (OR 1.04) were associated with mortality; age, gender, race, cancer, and acute illness type were not predictive. On admission, 79% of patients had orders indicating Full Code. During 60-day follow-up, 42% of patients discussed goals of care. Documented goals of care discussions were more common for decedents than survivors (70% vs. 28%, P < 0.001), as were orders for do not resuscitate/do not intubate (68% vs. 24%, P < 0.001), stopping cancer-directed therapy (29% vs. 10%, P < 0.001), specialty Palliative Care (79% vs. 44%, P < 0.001), and Hospice (68% vs. 14%, P < 0.001). CONCLUSION. Acute illness hospitalization is a sentinel event in Stage IV cancer. Short-term mortality is high; nutritional decline increases risk. For patients with Stage IV cancer, acute illness hospitalization should trigger goals of care discussions.

Objective This study aimed to quantify the 3D asymmetry of the maxilla in patients with unilateral cleft lip and palate (UCP) and investigate the defect factors responsible for the variability of the maxilla on the cleft side using a deep-learning-based CBCT image segmentation protocol. Setting and sample population Cone beam computed tomography (CBCT) images of 60 patients with UCP were acquired. The samples in this study consisted of 39 males and 21 females, with a mean age of 11.52 years (SD = 3.27 years; range of 8-18 years). Materials and methods The deep-learning-based protocol was used to segment the maxilla and defect initially, followed by manual refinement. Paired t-tests were performed to characterize the maxillary asymmetry. A multiple linear regression was carried out to investigate the relationship between the defect parameters and those of the cleft side of the maxilla. Results The cleft side of the maxilla demonstrated a significant decrease in maxillary volume and length as well as alveolar length, anterior width, posterior width, anterior height and posterior height. A significant increase in maxillary anterior width was demonstrated on the cleft side of the maxilla. There was a close relationship between the defect parameters and those of the cleft side of the maxilla. Conclusions Based on the 3D volumetric segmentations, significant hypoplasia of the maxilla on the cleft side existed in the pyriform aperture and alveolar crest area near the defect. The defect structures appeared to contribute to the variability of the maxilla on the cleft side.

Objective To investigate the potential of EEG multiscale entropy and complexity as biomarkers in infantile spasms. Methods We collected EEG data retrospectively from 16 newly diagnosed patients, 16 age- and gender-matched healthy controls, and 15 drug-resistant patients. The multiscale entropy (MSE) and total EEG complexity before anti-epileptic drug (AED) treatment, before adrenocorticotropic hormone (ACTH) treatment, 14 days after ACTH therapy, and after 6 months of follow-up were calculated. Results The total EEG complexity of 16 newly diagnosed infantile spasms patients was lower than the 16 healthy controls (median [IQR]: 351.5 [323.1–388.1] vs 461.6 [407.7–583.4]). The total EEG complexity before treatment was higher in the six patients with good response to AED than the 10 patients without response (median [IQR]: 410.0 [388.1–475.0] vs 344.5 [319.6–352.0]). The total EEG complexity before and after 14-days of ACTH therapy was not different between 13 ACTH therapy responders and nine non-responders. After 6-months follow-up, the total EEG complexity of ACTH therapy responders were higher than non-responders (median [IQR]: 598.5 [517.4–623.3] vs 448.6 [347.1–536.3]). Conclusions The total EEG complexity before AED and 6 months after ACTH are associated with spasm-freedom. Significance The total EEG complexity is a potential biomarker to predict and monitor the treatment effect in infantile spasms.

Background The ability to estimate skeletal maturity using a knee radiograph would be useful in anterior cruciate ligament (ACL) injuries and limb-length discrepancy in immature patients. Currently, a quick, accurate, and reproducible method is lacking. Methods Serial knee radiographs made 3 years before to 2 years following the chronologic age associated with 90% of final height (an enhanced skeletal maturity gold standard compared with peak height velocity) were analyzed in 78 children. The Pyle and Hoerr (PH) knee method was simplified by developing discrete stages for the distal part of the femur, the proximal part of the tibia, the proximal part of the fibula, and the patella. The Roche-Wainer-Thissen (RWT) knee method was simplified from the 36 original parameters to 14 parameters by removing parameters that were poorly defined, were not relevant to the peripubertal age range, were poorly correlated with 90% final height, or were poorly reliable on a 20-radiograph pilot analysis. We also compared the recently described central peak value (CPV) of the distal part of the femur. The Greulich and Pyle (GP) left-hand bone age was included for comparison. Results In this study, 326 left knee radiographs from 41 girls (age range, 7 to 15 years) and 37 boys (age range, 9 to 17 years) were included. Stepwise linear regression showed higher correlation in predicting years from 90% final height using the modified RWT and demographic characteristics (R2 = 0.921) compared with demographic characteristics alone (R2 = 0.840), CPV and demographic characteristics (R2 = 0.866), GP and demographic characteristics (R2 = 0.899), and PH and demographic characteristics (R2 = 0.902). Seven parameters were excluded from the RWT and demographic characteristics model using stepwise linear regression and generalized estimating equations analysis, leaving 7 parameters (2 femoral, 4 tibial, and 1 fibular) in the final model. Compared with RWT and demographic characteristics (R2 = 0.921), there were minimal incremental increases by adding CPV (R2 = 0.921), GP (R2 = 0.925), or PH (R2 = 0.931). Conclusions This large analysis of knee skeletal maturity systems isolated 7 discrete radiographic knee parameters that theoretically outperform the GP bone age in estimating skeletal maturity. Clinical relevance We present a modified knee skeletal maturity system that can potentially preclude the need for additional imaging of the hand and wrist in reliably estimating skeletal maturity.

Alanine aminotransferase (ALT) is a cost-effective screening test for asymptomatic liver diseases. The aims of this study are to redefine the ULNs of ALT using the 2010-2012 Nutrition and Health Survey in Taiwan (NAHSIT) database and to determine whether the updated ULNs can better screen for metabolic dysfunction-associated fatty liver disease (MAFLD) in obese children.Reference data were obtained from 2895 NAHSIT participants (1442 boys, 1453 girls) aged 6-18 years. Participants with any of MAFLD-related metabolic risk factors, including overweight/obesity, elevated triglyceride, low high-density lipoprotein cholesterol and high fasting glucose, were excluded. This study compared the sensitivities of different ULNs of ALT for detecting MAFLD in our previously established cohort of obese children.The ULNs of ALT defined as the 95th percentile in metabolically healthy NAHSIT participants were 23 IU/L for boys and 18 IU/L for girls. When using the updated ULNs, the percentages of elevated ALT levels were 13.0% in boys and 7.8% in girls of all NAHSIT participants. When using the updated ULNs of ALT to detect MAFLD in obese children, the sensitivity was 84.0% in boys and 74.3% in girls. In contrast, when using the conventional ALT cutoff (40 IU/L), the sensitivity decreased to 61.4% in boys and 36.4% in girls.After taking into account MAFLD-related metabolic risk factors, the ULNs of ALT are 23 IU/L for boys and 18 IU/L for girls in Taiwan. The updated ULNs may be better cutoffs for screening MAFLD in obese children.

Background: We found that Taiwanese adults carrying genotypes of UDP-glucuronosyltransferase (UGT) 1A1 with enzyme activity ≤40% of normal were at high risk for developing Gilbert's syndrome. However, the relationship between UGT1A1 activity and neonatal hyperbilirubinemia has never been evaluated for Taiwanese. Methods: We enrolled 141 hyperbilirubinemic neonates partially fed supplementary infant formula and 432 controls; and 112 hyperbilirubinemic neonates exclusively breastfed and 493 controls. The five single nucleotide polymorphisms (SNPs) at nucleotides −53, 211, 686, 1091 and 1456 in the UGT1A1 gene were determined and UGT1A1 activity was estimated. Odds ratios (ORs) of variation status in the UGT1A1 gene and enzyme activity for the development of neonatal hyperbilirubinemia were calculated, respectively. Results: For neonates partially fed supplementary infant formula, the adjusted OR (AOR) for the development of hyperbilirubinemia was significantly higher in the neonates carrying the homozygous variation (211AA) in the UGT1A1 gene than for those carrying the wild type (AOR = 6.00, p

BACKGROUND: Although medications to treat opioid use disorder (MOUD) are the standard of care during pregnancy, there are many potential gaps in the cascade of care for pregnant people experiencing incarceration. METHODS: We conducted a retrospective cohort study of pregnant people with opioid use disorder incarcerated in a Southeastern women’s prison from 2016–2019. The primary outcomes were access to MOUD during incarceration and continuity in the community. We used descriptive statistics to summarize aspects of our sample and logistic regression to identify predictors of MOUD receipt during incarceration. RESULTS: Of the 279 pregnant people with OUD included in the analysis, only 40.1% (n=112) received MOUD during incarceration, including 67 (59.8%) who received methadone and 45 (40.1%) who received buprenorphine. Less than one-third of the participants were referred to a community MOUD provider (n=83, 30%) on return to the community. Significant predictors of MOUD receipt included medium/close custody level during incarceration, incarceration during the latter portion of the study period, pre-incarceration heroin use, and receipt of pre-incarceration MOUD. CONCLUSIONS: Although prisons can serve as an important site of retention in MOUD for some pregnant people, there were substantial gaps in initiation of MOUD and retention in MOUD among pregnant people with OUD imprisoned in the Southeast during the study period.

Colorectal cancer (CRC) is a major cause of cancer mortality and morbidity. Despite advances in chemotherapy and targeted therapy, unsustainable clinical benefit was noted due to recurrence and therapy resistance. The immune status of the cancer patient may affect the effectiveness of disease treatments. The dynamic change in the T-cell receptor (TCR) repertoire might be a clinical parameter for monitoring treatment responses. In this study, we aimed to determine the characteristics and clinical significance of the TCR repertoire in patients with unresectable metastatic colorectal cancer (mCRC). Herein, we comprehensively profile 103 peripheral blood samples from 20 healthy controls and 16 CRC patients with a follow-up of 98 to 452 days to identify hypervariable rearrangements of the TCRα and TCRβ repertoires using high-throughput sequencing. We found that TCRα repertoires, TCRβ repertoires, and CDR3 clonotypes were altered in mCRC patients compared with healthy controls. The diversity of TCR repertoires and CDR3 clonotypes decreased in most mCRC patients after therapy. Furthermore, compared with baseline TCR diversity, patients whose TCR diversity dropped considerably during therapy had better treatment responses, including lower CEA and CA19-9 levels and smaller tumor sizes. TCR baseline diversity was also significantly associated with partial response (PR) status (odds ratio: 5.29, p = 0.04). In conclusion, the present study demonstrated the association between dynamic changes in TCR diversity during chemotherapy and clinical outcomes as well as the potential utility of the TCR repertoire in predicting the prognosis of cancer treatment.

strongBACKGROUND/strongLow back pain (LBP) is regarded as a frequent disease that causes disability. We aimed to explore the effect of naringin on intervertebral disc degeneration (IDD) in IL-1ß-induced human nucleus pulposus (NP) cells and its corresponding molecular mechanisms.strongMATERIAL AND METHODS/strongHuman NP cells were identified by toluidine blue and Safranin O staining. Cell viability was determined by MTT assay. The expression levels of matrix metalloproteinases (MMP-3, MMP-13, ADAMTS-4, ADAMTS-5, collagen II, aggrecan), inflammatory genes (tumor necrosis factor [TNF]-alpha, interleukin [IL]-6), kappa B kinase alpha (IkappaBalpha), p65 and p53 were determined by quantitative real-time polymerase chain reaction (qPCR) and western blotting. Immunofluorescence study was performed to detect the position and expression of p65 protein in IL-1ß-induced human NP cells.strongRESULTS/strongHuman NP cells were successfully separated from intervertebral disc tissue. We found that naringin could significantly reduce the expressions of matrix metalloproteinases (MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5) and inflammatory genes in IL-1ß-stimulated human NP cells, while collagen II and aggrecan were increased at mRNA and protein level. Immunofluorescence showed that naringin pretreatment decreased the p65 protein expression in the nucleus and suppressed the phosphorylation of IkappaBalpha and p65.strongCONCLUSIONS/strongThese results demonstrated that naringin could attenuate matrix metalloproteinase catabolism and inflammation in IL-1ß-treated human nucleus pulposus cells via downregulating NF-kappaB pathway and p53 expression, suggesting that naringin has the potential to prevent and treat IDD.

In this study, the performance of machine learning in classifying parotid gland tumors based on diffusion-related features obtained from the parotid gland tumor, the peritumor parotid gland, and the contralateral parotid gland was evaluated. Seventy-eight patients participated in this study and underwent magnetic resonance diffusion-weighted imaging. Three regions of interest, including the parotid gland tumor, the peritumor parotid gland, and the contralateral parotid gland, were manually contoured for 92 tumors, including 20 malignant tumors (MTs), 42 Warthin tumors (WTs), and 30 pleomorphic adenomas (PMAs). We recorded multiple apparent diffusion coefficient (ADC) features and applied a machine-learning method with the features to classify the three types of tumors. With only mean ADC of tumors, the area under the curve of the classification model was 0.63, 0.85, and 0.87 for MTs, WTs, and PMAs, respectively. The performance metrics were improved to 0.81, 0.89, and 0.92, respectively, with multiple features. Apart from the ADC features of parotid gland tumor, the features of the peritumor and contralateral parotid glands proved advantageous for tumor classification. Combining machine learning and multiple features provides excellent discrimination of tumor types and can be a practical tool in the clinical diagnosis of parotid gland tumors.

Objective The goal of the present study was to observe the effect of autophagy in tibial plateau chondrocytes on apoptosis in spontaneous knee osteoarthritis (OA) in guinea pigs. Design Fifty 2-month-old female Hartley guinea pigs were divided into a normal group (10 animals, all euthanized after 7 months) and an OA group (40 animals, 10 of which were euthanized after 10 months). Immunohistochemistry, RT-qPCR and Western blotting were used to evaluate autophagy levels, intracellular glycogen accumulation and apoptosis in tibial plateau chondrocytes in vivo and in vitro. The remaining 30 guinea pigs in the OA group were divided into 3 groups: a rapamycin group, a normal saline group, and a 3-methyladenine (3-MA) group. Intracellular glycogen accumulation and chondrocyte apoptosis were assessed by altering the level of autophagy in chondrocytes in vivo. Results When spontaneous OA occurred in guinea pigs, autophagy levels in tibial plateau chondrocytes decreased, while intracellular glycogen accumulation and the rate of chondrocyte apoptosis increased. After enhancing the level of autophagy in tibial plateau chondrocytes in guinea pigs with OA, intracellular glycogen accumulation and the rate of chondrocyte apoptosis decreased, while inhibiting autophagy had the opposite effects. Conclusion The results indicate that the function of autophagy in chondrocytes may at least partly involve the catabolism of glycogen. In guinea pigs with OA, the level of autophagy in tibial plateau chondrocytes decreased, and chondrocytes were unable to degrade intracellular glycogen into glucose, leading to less energy for chondrocytes and increased apoptosis.

Importance Office blood pressure (BP) measurements are not the most accurate method to diagnose hypertension. Home BP monitoring (HBPM) and 24-hour ambulatory BP monitoring (ABPM) are out-of-office alternatives, and ABPM is considered the reference standard for BP assessment. Objective To systematically review the accuracy of oscillometric office and home BP measurement methods for correctly classifying adults as having hypertension, defined using ABPM. Data Sources PubMed, Cochrane Library, Embase, ClinicalTrials.gov, and DARE databases and the American Heart Association website (from inception to April 2021) were searched, along with reference lists from retrieved articles. Data Extraction and Synthesis Two authors independently abstracted raw data and assessed methodological quality. A third author resolved disputes as needed. Main Outcomes and Measures Random effects summary sensitivity, specificity, and likelihood ratios (LRs) were calculated for BP measurement methods for the diagnosis of hypertension. ABPM (24-hour mean BP ≥130/80 mm Hg or mean BP while awake ≥135/85 mm Hg) was considered the reference standard. Results A total of 12 cross-sectional studies (n = 6877) that compared conventional oscillometric office BP measurements to mean BP during 24-hour ABPM and 6 studies (n = 2049) that compared mean BP on HBPM to mean BP during 24-hour ABPM were included (range, 117-2209 participants per analysis); 2 of these studies (n = 3040) used consecutive samples. The overall prevalence of hypertension identified by 24-hour ABPM was 49% (95% CI, 39%-60%) in the pooled studies that evaluated office measures and 54% (95% CI, 39%-69%) in studies that evaluated HBPM. All included studies assessed sensitivity and specificity at the office BP threshold of 140/90 mm Hg and the home BP threshold of 135/85 mm Hg. Conventional office oscillometric measurement (1-5 measurements in a single visit with BP ≥140/90 mm Hg) had a sensitivity of 51% (95% CI, 36%-67%), specificity of 88% (95% CI, 80%-96%), positive LR of 4.2 (95% CI, 2.5-6.0), and negative LR of 0.56 (95% CI, 0.42-0.69). Mean BP with HBPM (with BP ≥135/85 mm Hg) had a sensitivity of 75% (95% CI, 65%-86%), specificity of 76% (95% CI, 65%-86%), positive LR of 3.1 (95% CI, 2.2-4.0), and negative LR of 0.33 (95% CI, 0.20-0.47). Two studies (1 with a consecutive sample) that compared unattended automated mean office BP (with BP ≥135/85 mm Hg) with 24-hour ABPM had sensitivity ranging from 48% to 51% and specificity ranging from 80% to 91%. One study that compared attended automated mean office BP (with BP ≥140/90 mm Hg) with 24-hour ABPM had a sensitivity of 87.6% (95% CI, 83%-92%) and specificity of 24.1% (95% CI, 16%-32%). Conclusions and Relevance Office measurements of BP may not be accurate enough to rule in or rule out hypertension; HBPM may be helpful to confirm a diagnosis. When there is uncertainty around threshold values or when office and HBPM are not in agreement, 24-hour ABPM should be considered to establish the diagnosis.

Background Regular physical activity is an important component of healthy living and wellbeing. Current guidelines recommend that adults participate in at least 150 min of moderate or vigorous-intensity physical activity weekly. In spite of the benefits, just over half of U.S. adults meet these recommendations. Calorie-only food labels at points of food purchase have had limited success in motivating people to change eating behaviors and increase physical activity. One new point of purchase approach to promote healthy behaviors is the addition of food labels that display the physical activity requirement needed to burn the calories in a food item (e.g. walk 15 min). Methods The Physical Activity Calorie Expenditure (PACE) Study compared activity-based calorie-expenditure food labels with calorie-only labels at three Blue Cross and Blue Shield of North Carolina worksite cafeterias. After 1 year of baseline data collection, one cafeteria had food items labeled with PACE labels, two others had calorie-only food labels. Cohort participants were asked to wear an accelerometer and complete a self-report activity questionnaire on two occasions during the baseline year and twice during the intervention year. Results A total of 366 study participants were included in the analysis. In the PACE-label group, self-reported physical activity increased by 13–26% compared to the calorie-only label group. Moderate-to-vigorous physical activity (MVPA) increased by 24 min per week in the PACE-label group compared to the calorie-label group (p = 0.06). Changes in accelerometer measured steps, sedentary time, and MVPA had modest increases. Change ranged from 1 to 12% with effect size values from 0.08 to 0.15. Baseline physical activity level significantly moderated the intervention effects for all physical activity outcomes. Participants in both label groups starting in the lowest tertile of activity saw the largest increase in their physical activity. Conclusion Results suggest small positive effects for the PACE labels on self-reported and objective physical activity measures. Minutes of weekly MVPA, strength training, and exercise activities showed modest increases. These results suggest that calorie-expenditure food labels may result in some limited increases in physical activity.

Breast cancer is a main cause of disease and death for women globally. Because of the limitations of traditional mammography and ultrasonography, magnetic resonance imaging (MRI) has gradually become an important radiological method for breast cancer assessment over the past decades. MRI is free of the problems related to radiation exposure and provides excellent image resolution and contrast. However, a disadvantage is the injection of contrast agent, which is toxic for some patients (such as patients with chronic renal disease or pregnant and lactating women). Recent findings of gadolinium deposits in the brain are also a concern. To address these issues, this paper develops an intravoxel incoherent motion- (IVIM-) MRI-based histogram analysis approach, which takes advantage of several hyperspectral techniques, such as the band expansion process (BEP), to expand a multispectral image to hyperspectral images and create an automatic target generation process (ATGP). After automatically finding suspected targets, further detection was attained by using kernel constrained energy minimization (KCEM). A decision tree and histogram analysis were applied to classify breast tissue via quantitative analysis for detected lesions, which were used to distinguish between three categories of breast tissue: malignant tumors (i.e., central and peripheral zone), cysts, and normal breast tissues. The experimental results demonstrated that the proposed IVIM-MRI-based histogram analysis approach can effectively differentiate between these three breast tissue types.

Purpose:To examine the association between dry eye and diabetes mellitus among a large North Carolina patient population. Methods:A retrospective cross-sectional study of patients seen within the University of North Carolina medical system between July 1, 2008, and September 1, 2017, was performed. De-identified medical records contained within the Carolina Data Warehouse of adult patients who have had an ocular evaluation were studied. Four categories of disease states were identified by ICD-9 and ICD-10 codes. Patients were grouped based on being diagnosed with Dry Eye Disease (ICD-9: 375.15, 370.33, and ICD-10: H04.12, H16.221), Diabetes Mellitus (ICD-9: 250.00-250.93 and ICD-10: E08-E11, E13), neither, or both diseases. Odds ratios of the association between diabetes and dry eye were calculated for the following racial/ethnic groups: Non-Hispanic White, Non-Hispanic Black/African American, Asian, and Hispanic. Results:A total of 81,480 patients were included in the analysis; of those, 8978 patients had dry eye disease and 18,361 patients had diabetes. The remaining 54,141 patients had neither disease. Dry eye prevalence among patients with diabetes was 14.39% (95% CI: 13.89-14.91%) and 10.11% (95%CI: 9.88-10.35%) among patients without diabetes. The odds of a patient with diabetes having dry eye are 1.15 (95% CI: 1.09-1.21) times that of a patient without diabetes. Asian patients with diabetes demonstrated the highest odds of having dry eye at 1.49 (95% CI: 1.12-1.98). Conclusions:Dry eye is common among patients with diabetes, and the association between these diseases is strongest among Asian patients. Race and ethnicity are important demographic factors that may guide providers in the diagnosis and treatment of dry eye in the setting of diabetes.

Orthodontics is evolving with advances in 3D imaging, additive fabrication, digital scanning, and treatment planning. With digital tools, orthodontic treatment may become more predictable, efficient, and effective while reducing side-effects. These technologies are affecting patient care, but knowledge of their adoption patterns and influence is incomplete. We aimed to identify adoption decision makers, information sources, perspectives, incentives, and barriers.Twenty-four privately practicing orthodontists were interviewed in a semistructured format following a topic guide. Interview transcripts were analyzed to identify factors in technology adoption and its perceived influence on practice. Thematic patterns were established through iterative systematic analysis, and qualitative validity was ensured with researcher triangulation.Qualitative interviews revealed that orthodontists make purchasing decisions independently from staff, after consulting other dentists and company representatives. Meetings, residency training, and continuing education courses are influential information sources, whereas research literature is not. Early and middle adopters are integrating digital imaging, planning, and fabrication technologies into practice and view enhanced ease of use, capabilities, performance, and procedural efficiency as primary incentives to adoption. Improving outcomes and patient comfort are not frequently cited as incentives, and all interviewees view cost as the largest barrier. Orthodontists positively perceive the influence of technology on their practices, but are concerned that further innovation and direct-to-consumer products will cause loss of market share.CAD/CAM appliances, 3D imaging, and digital treatment planning are viewed as future standards of care and are increasingly being incorporated into the orthodontic office. Understanding the technology adoption process can guide innovation to improve treatment and ease the transition into a digital workflow.

Objective To examine the effect of clinical use on both force retention and the deactivation of closed-coil nickel-titanium (NiTi) springs in a 16-week trial. Methods The force-activation curves for NiTi springs were determined before and after clinical use. The rate of tooth movement and maximum force (MF), hysteresis between activation and deactivation, and mean force of the deactivation plateau (MDF) were examined and correlated as a function of 4, 8, 12 and 16 weeks of clinical use. To recover the force properties, the springs were heat treated at 100°C and the results were compared with the preceding data. Results A total of 36 springs were analysed. The MF loss after use was 60, 74, 55, and 48 g for the 4-, 8-, 12- and 16-week springs, respectively. Heat treating had little effect on the MF. Clinical use lowered hysteresis by a mean of 180 g*mm compared with the pre-clinical use data, and heat treating increased the hysteresis by a mean of 59 g*mm above the post clinic testing data. The MDF was nominally 100 g less than the MF. Teeth moved approximately 1 mm/month, independent of the force loss. Conclusions The loss of MF and the lowering of the MDF was not time dependent. Heat treating can partially recover the mechanical properties of the used springs.

CONTEXT: Persons with late-stage dementia have limited access to palliative care. OBJECTIVE: To test dementia-specific specialty palliative care triggered by hospitalization. METHODS: This pilot randomized controlled trial enrolled 62 dyads of persons with late-stage dementia and family decision-makers on admission to hospital. Intervention dyads received dementia-specific specialty palliative care consultation plus post-acute transitional care. Control dyads received usual care and educational information. The primary outcome was 60-day hospital or emergency department visits. Secondary patient and family-centered outcomes were patient comfort, family distress, palliative care domains addressed in the treatment plan, and access to hospice or community-based palliative care. Secondary decision-making outcomes were discussion of prognosis, goals of care, completion of Medical Orders for Scope of Treatment (MOST), and treatment decisions. RESULTS: Of 137 eligible dyads, 62 (45%) enrolled. The intervention proved feasible, with protocol completion ranging from 77% (family 2-week call) to 93% (initial consultation). Hospital and emergency department visits did not differ (intervention vs control, 0.68 vs 0.53 transfers per 60 days, p=0.415). Intervention patients had more palliative care domains addressed, and were more likely to receive hospice (25% vs 3%, p

Automated whole breast ultrasound (ABUS) has been widely used as a screening modality for examination of breast abnormalities. Reviewing hundreds of slices produced by ABUS, however, is time consuming. Therefore, in this paper, a fast and effective computer-aided detection system based on 3-D convolutional neural networks (CNNs) and prioritized candidate aggregation is proposed to accelerate this reviewing. First, an efficient sliding window method is used to extract volumes of interest (VOIs). Then, each VOI is estimated the tumor probability with a 3-D CNN, and VOIs with higher estimated probability are selected as tumor candidates. Since the candidates may overlap each other, a novel scheme is designed to aggregate the overlapped candidates. During the aggregation, candidates are prioritized based on estimated tumor probability to alleviate over-aggregation issue. The relationship between the sizes of VOI and target tumor is optimally exploited to effectively perform each stage of our detection algorithm. On evaluation with a test set of 171 tumors, our method achieved sensitivities of 95% (162/171), 90% (154/171), 85% (145/171), and 80% (137/171) with 14.03, 6.92, 4.91, and 3.62 false positives per patient (with six passes), respectively. In summary, our method is more general and much faster than preliminary works and demonstrates promising results.

Cerebral small vessel disease is one of the most common causes of cognitive decline and stroke. While several lines of evidence have established a relationship between inflammation and cerebrovascular pathology, the mechanistic link has not yet been elucidated. Recent studies suggest activation of immune mediators, including the soluble form of triggering receptor expressed on myeloid cells 2 (TREM2), may be critical regulators. In this study, we compared the plasma levels of soluble TREM2 and its correlations with neuroimaging markers and cerebral amyloid load in 10 patients with Alzheimer’s disease and 66 survivors of spontaneous intracerebral haemorrhage with cerebral amyloid angiopathy or hypertensive small vessel disease, two of the most common types of sporadic small vessel disease. We performed brain MRI and 11C-Pittsburgh compound B PET for all participants to evaluate radiological small vessel disease markers and cerebral amyloid burden, and 18F-T807 PET in a subgroup of patients to evaluate cortical tau pathology. Plasma soluble TREM2 levels were comparable between patients with Alzheimer’s disease and small vessel disease (P = 0.690). In patients with small vessel disease, plasma soluble TREM2 was significantly associated with white matter hyperintensity volume (P Our results indicate plasma soluble TREM2 is associated with white matter hyperintensity independent of amyloid and tau pathology. These findings highlight the potential utility of plasma soluble TREM2 as a strong predictive marker for small vessel disease-related white matter injury and hold clinical implications for targeting the innate immune response when treating this disease.

BACKGROUND We assessed patterns of health care utilization to further characterize chronic comorbidities prior to sudden death. METHOD From March 1, 2013, through February 28, 2015, all out-of-hospital deaths aged 18-64 reported by emergency medical services in Wake County, North Carolina, were screened to adjudicate 399 sudden death victims. Retrospective analysis of clinical records on victims determined health care utilization. Health care utilization frequency was assessed by latent growth curve analysis. RESULTS Medical records were available for 264 victims (aged 53.5 ± 9.2) who were predominantly male (65%) and white (64%). Of these, 210 (80%) victims had at least one visit within two years of death and 73 (28%) had a visit within one month of death. Over the two years prior to death, there was an increasing frequency of doctor visits (P < .001). Victims averaged 3.7 ± 4.6 yearly visits and were categorized into low (0.4 visits/year), medium (3.3 visits/year), and high (11.4 visits/year) tiers of visit frequency. The high visit tier had a greater prevalence of coronary artery disease (38%), hypertension (80%), diabetes (58%), depression (74%), anxiety (64%), and substance misuse (46%) (P < .001). LIMITATIONS Those who were non-free-living, minors, without formal medical records, and adults aged 65 and older were excluded from the analysis. CONCLUSIONS A majority of sudden death victims utilized health care within two years prior to death and had comorbidities that may have contributed to their unexpected death. The increasing frequency of visits prior to death provided an opportunity for health care providers to address potential victims' chronic medical conditions to potentially prevent death.

Objectives Diabetes mellitus (DM) increases the risk of cardiovascular disease and is associated with sudden death. Mental illness among individuals with DM may confound medical care. This study assessed the association of mental illness with DM and poorly controlled DM in sudden death victims. Methods We screened out-of-hospital deaths ages 18 to 64 years in Wake County, North Carolina from 2013 to 2015 to adjudicate sudden deaths. We abstracted demographics and clinical characteristics from health records. Mental illness included anxiety, schizophrenia, bipolar disorder, or depression. Poorly controlled DM was defined as a hemoglobin A1c >8 or taking ≥3 medications for glycemic control. Logistic regression assessed the association between DM and mental illness. Results Among victims with available records, 109 (29.4%) had DM. Of those, 62 (56.9%) had mental illness. Mental illness was present in 53.42% and 63.89% of victims with mild and poorly controlled DM, respectively. Mental illness was associated with DM (adjusted odds ratio 2.46, 95% confidence interval 1.57-3.91). Victims with poorly controlled DM were more likely to have mental illness (adjusted odds ratio 2.66, 95% confidence interval 1.14-6.18). Conclusions DM is a common comorbid condition in sudden death victims. Among victims, mental illness is associated with the control of DM. Early management of comorbid mental illnesses may improve the care of patients with DM and reduce the incidence of sudden death.

AIM Good sleep quality is essential to physical and mental-health-related quality of life. The purpose of this study was to evaluate the effects of a walking exercise in relieving sleep quality, fatigue, and depression in new mothers during the postpartum period. METHODS This quasi-experimental study was conducted at a teaching hospital in southern Taiwan. One hundred and four eligible postpartum women with poor sleep quality (Postpartum Sleep Quality Scale; PSQS score ≧16) were assigned to either the experimental group (n = 50) or the control group (n = 54) according to their individual preferences. The participants in the experimental group participated in a 12-week stride walking exercise intervention. The control group did not receive any exercise intervention. The PSQS, Postpartum Fatigue Scale, and Edinburgh Postnatal Depression Scale were used to assess outcomes. RESULTS Repeated measures ANOVA demonstrated that the experimental group participants perceived milder physical symptoms associated with sleep inefficiency at 4-week posttest (F = 7.25, p

We have previously demonstrated calcimimetics optimize the balance between osteoclastic bone resorption and osteoblastic mineralization through upregulating Wingless and int-1 (Wnt) signaling pathways in the mouse and cell model. Nonetheless, definitive human data are unavailable concerning therapeutic effects of Cinacalcet on chronic kidney disease and mineral bone disease (CKD-MBD) and osteoclast&ndash, osteoblast interaction. We aim to investigate whether Cinacalcet therapy improves bone mineral density (BMD) through optimizing osteocytic homeostasis in a human model. Hemodialysis patients with persistently high intact parathyroid hormone (iPTH) levels &gt, 300 pg/mL for more than 3 months were included and received fixed dose Cinacalcet (25 mg/day, orally) for 6 months. Bone markers presenting osteoclast&ndash, osteoblast communication were evaluated at baseline, the 3rd and the 6th month. Eighty percent of study patients were responding to Cinacalcet treatment, capable of improving BMD, T score and Z score (16.4%, 20.7% and 11.1%, respectively). A significant correlation between BMD improvement and iPTH changes was noted (r = &minus, 0.26, p &lt, 0.01). Nonetheless, baseline lower iPTH level was associated with better responsiveness to Cinacalcet therapy. Sclerostin, an inhibitor of canonical Wnt/&beta, catenin signaling, was decreased from 127.3 &plusmn, 102.3 pg/mL to 57.9 &plusmn, 33.6 pg/mL. Furthermore, Wnt-10b/Wnt 16 expressions were increased from 12.4 &plusmn, 24.2/166.6 &plusmn, 73.3 pg/mL to 33.8 &plusmn, 2.1/217.3 &plusmn, 62.6 pg/mL. Notably, procollagen type I amino-terminal propeptide (PINP), a marker of bone formation and osteoblastic activity, was increased from baseline 0.9 &plusmn, 0.4 pg/mL to 91.4 &plusmn, 42.3 pg/mL. In contrast, tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), a marker of osteoclast activity, was decreased from baseline 16.5 &plusmn, 0.4 mIU/mL to 7.7 &plusmn, 2.2 mIU/mL. Moreover, C-reactive protein levels were suppressed from 2.5 &plusmn, 0.6 to 0.8 &plusmn, 0.5 mg/L, suggesting the systemic inflammatory burden may be benefited after optimizing the parathyroid&ndash, bone axis. In conclusion, beyond iPTH suppression, our human model suggests Cinacalcet intensifies BMD through inhibiting sclerostin expression and upregulating Wnt-10b/Wnt 16 signaling that activates osteoblastic bone formation and inhibits osteoclastic bone resorption and inflammation. From the perspective of translation to humans, this research trial brings a meaningful insight into the osteoblast&ndash, osteoclast homeostasis in Cinacalcet therapy for CKD-MBD.

Objective Human papillomavirus (HPV) testing as the primary cervical cancer screening followed by reflex cytology if high-risk HPV is present (hrHPV+) is recently adopted in some countries. However, reflex cytology's sensitivity is variable, and a suitable triage approach for hrHPV+ remains controversial. Here, we compared the performance of three triage tools in hrHPV+ women. Methods Three triage tools—cytology, HPV16/18 genotyping, and DNA methylation biomarker PAX1m—were analyzed for their clinical performance in hrHPV+ women. In addition, women without cervical cancer at enrollment were followed for histologically confirmed high-grade cervical intraepithelial neoplasia or worse (CIN3+) annually using Papanicolaou smear. Results Of 4762 women aged ≥20 years enrolled, 502 (10.5%) were hrHPV+. PAX1m and cytology demonstrated similar accuracy (>90%), sensitivity (>78%), and specificity (>92%) as triage tools in 429 hrHPV+ women aged 30–64 years. PAX1m had better accuracy and specificity (91.6% and 92.5%, respectively) than HPV16/18 (76.9% and 76.8%, respectively). The incidence of CIN3+ among hrHPV+ women was 10.7 cases/1000 person-years. The incidence was significantly greater in PAX1m-positive women than in PAX1m-negative women. Conclusions PAX1m has comparable clinical performance to cytology and better accuracy and specificity than HPV16/18 as the triage tool for detecting CIN3+ in hrHPV+ women. The PAX1m assay is thus a promising molecular-based triage tool for early detection of CIN and predicting disease progression in hrHPV+ women. It can be especially useful in countries where adequate cytology-based infrastructure is lacking, such as some Southeast Asian countries, for cervical cancer screening and prevention.

To investigate the internal exposure levels of manganese(Mn), cobalt(Co), selenium(Se) and molybdenum(Mo) in blood and urine among the general population in parts of Shaanxi Province, and thereby to analyze their population distribution characteristics.In 2017, a total of 720 subjects of general people aged 3-79 years were recruited from 5 counties in Shaanxi Province, by stratified random sampling method, blood and urine samples were collected, and the contents of Mn, Co, Se and Mo in blood and urine samples were detected by inductively coupled plasma mass spectrometry(ICP-MS). The test result were statistically analyzed according to different genders, regions and age groups.Among general people in Shaanxi Province, the median of Mn in blood and urine were separately 8. 43 and 0. 60 μg/L. The median of Mn in blood among males and females were 7. 99 and 8. 81 μg/L, the difference was statistically significant(Plt;0. 05), the difference of blood Mn between urban and rural areas was statistically significant(Plt;0. 05). The median of Co in blood and urine were separately 0. 13 and 0. 17 μg/L, the median of Co in blood among males and females were 0. 12 and 0. 15 μg/L, the median of Co in urine among males and females were 0. 16 and 0. 20 μg/L, the differences were statistically significant(Plt;0. 05), the differences of blood Co and urine Co in urban and rural areas were statistically significant(Plt;0. 05). The median of Se concentration in blood and urine were separately 73. 20 and 13. 30 μg/L, the median of Se in urine among males and females were 14. 40 and 12. 40 μg/L, the difference were statistically significant(Plt;0. 05), the differences of blood Se and urine Se in urban and rural areas were statistically significant(Plt;0. 05). The median of Mo concentration in blood and urine were separately 0. 60 and 50. 40 μg/L, the median of Mo in urine among males and females were 56. 60 and 43. 00 μg/L, the difference was statistically significant(Plt;0. 05), the difference of blood Mo between urban and rural areas was statistically significant(Plt;0. 05). Within the same gender, all indexes in whole blood(except female blood Se) were statistically significant among age groups(Plt;0. 05). The differences of male urine Co, urine Se, urine Mo and female urine Co among age groups were statistically significant(Plt;0. 05).Among general population in Shaanxi Province, the Mn, Co, Se and Mo levels in blood and urine are varied by gender age and area, the blood Se level is relatively low.

Background In adults, the time of day for LT does not affect post-transplant outcomes. Whether this is true or not in children is unknown. In this study, we aimed to evaluate if weekend and weeknight liver transplants are associated with worse patient and graft survival in children. Methods We interrogated the UNOS database for outcomes of pediatric liver transplants that occurred between 1988 and 2018. We excluded liver transplants in patients >17 years as well as all multiple organ transplants. We compared weeknight and weekday, as well as weekend transplant operations. We used Cox proportional hazard ratios to determine patient and graft survival by 7, 30, 90, and 365 days post-transplant after controlling for confounding factors. Results In total, 12,610 pediatric liver transplants were included in the analysis. A total of 4590 transplants occurred during weekdays, 3671 transplants occurred during weeknights, and 4349 occurred during weekends. After controlling for confounding variables, 1-year patient survival was not associated with worse outcomes if the transplant occurred on the weeknight (HR 0.94, 95%CI 0.74-1.21) or weekend (HR 0.95, 95%CI 0.75-1.20) compared to the weekday. One-year graft survival was also not associated with worse outcomes if the transplant occurred on the weeknight (HR 0.91, 95%CI 0.76-1.09) or weekend (HR 0.91, 95%CI 0.77-1.09) compared to the weekday. Conclusion Weekday, weeknight, and weekend procedures resulted in similar 1-year survival rates. Pediatric patient and graft survival outcomes are not affected by the time or day of surgery.

Background Areas of hypoxia are often found in triple-negative breast cancer (TNBC), it is thus more difficult to treat than other types of breast cancer, and may require combination therapies. A new strategy that combined bioreductive therapy with photodynamic therapy (PDT) was developed herein to improve the efficacy of cancer treatment. Our design utilized the characteristics of protoporphyrin IX (PpIX) molecules that reacted and consumed O2 at the tumor site, which led to the production of cytotoxic reactive oxygen species (ROS). The low microenvironmental oxygen levels enabled activation of a bioreductive prodrug, tirapazamine (TPZ), to become a toxic radical. The TPZ radical not only eradicated hypoxic tumor cells, but it also promoted therapeutic efficacy of PDT. Results To achieve the co-delivery of PpIX and TPZ for advanced breast cancer therapy, thin-shell hollow mesoporous Ia3d silica nanoparticles, designated as MMT-2, was employed herein. This nanocarrier designed to target the human breast cancer cell MDA-MB-231 was functionalized with PpIX and DNA aptamer (LXL-1), and loaded with TPZ, resulting in the formation of TPZ@LXL-1-PpIX-MMT-2 nanoVector. A series of studies confirmed that our nanoVectors (TPZ@LXL-1-PpIX-MMT-2) facilitated in vitro and in vivo targeting, and significantly reduced tumor volume in a xenograft mouse model. Histological analysis also revealed that this nanoVector killed tumor cells in hypoxic regions efficiently. Conclusions Taken together, the synergism and efficacy of this new therapeutic design was confirmed. Therefore, we concluded that this new therapeutic strategy, which exploited a complementary combination of PpIX and TPZ, functioned well in both normoxia and hypoxia, and is a promising medical procedure for effective treatment of TNBC.

Background Alpha-gal is an oligosaccharide implicated in delayed anaphylaxis following red meat consumption. Exposure to tick bites has been correlated with development of an allergic response to alpha-gal. However, evidence prospectively linking exposure to a single tick species and an immune response to alpha-gal is lacking. Methods We used serum samples from a prior study cohort of outdoor workers in North Carolina, USA, with high exposure to the lone star tick, Amblyomma americanum, to prospectively evaluate the relationship between tick bites and anti-alpha-gal IgE antibodies. Results Individuals who reported exposure to one or more tick bites were significantly more likely to have a positive change in anti-alpha-gal IgE compared to individuals with no reported tick bites. This relationship was not dependent on time. A trend toward increasing number of tick bites and increased anti-alpha-gal IgE levels was observed but not statistically significant. Conclusion To our knowledge, this is the first study to prospectively link documented exposure to A. americanum bites and increased sensitization to alpha-gal in a cohort of outdoor workers. Our results support the role of A. americanum as likely agents for eliciting an allergic response to red meat, and highlight the importance of preventing tick bites.

Background: Epidermal grafting with an automatic harvesting system has been reported as a simple and efficacious procedure for stable vitiligo. However, no prospective cohort study has quantitatively evaluated the color matching and extent of repigmentation in the head and neck area by this method. Objective: To evaluate the color matching and extent of repigmentation after pixel array epidermal grafting by image analysis software and physicians’ naked eye. Methods: Ten Asian patients with head and neck vitiligo lesions stable for at least 6 months were treated with pixel array epidermal grafting with an automatic harvesting system and post-grafting phototherapy. The patients were evaluated 1, 3, and 6 months post grafting for the percentage of repigmentation by blinded physicians’ assessment and image analysis software. The color matching index of repigmentation was evaluated by measuring the melanin index in the grafted area and the juxta non-vitiliginous area. Results: The average blister harvest time was 46.3 ± 9.7 min. The area percentile of repigmentation by the image analysis software were 32.3 ± 26.8, 64.6 ± 29.4, and 76.5 ± 25.9 at 1, 3, and 6 months post grafting, respectively. There were no significant differences between the physicians’ assessments and the results from the image analysis software. The change in the area percentile of repigmentation between 3 and 6 months post grafting was only statistically significant using image analysis software. The grafted area achieved a color match of 83.1 ± 13.4% that of the juxta non-vitiliginous area 6 months after grafting. Three patients had repigmentation of leukotrichia. Conclusion: By quantitative measurement, uniform pixel array micrografts provide a very good extent of repigmentation and color match in the head and neck area. Image analysis software revealed a steady increase in repigmentation after POM3 until POM6, which was not detected by subjective assessment.

PRéCIS:: This study addresses the paucity of literature examining glaucoma patients' distance from clinic on postoperative follow-up outcomes. Greater distance from clinic was associated with higher likelihood of loss to follow-up and missed appointments.To investigate the relationship of patient travel distance and interstate access to glaucoma surgery postoperative follow-up visit attendance.Retrospective longitudinal chart review of all noninstitutionalized adult glaucoma patients with initial trabeculectomies or drainage device implantations between April 4, 2014 and December 31, 2018. Patients were stratified into groups on the basis of straight-line distance from residence to University of North Carolina at Chapel Hill's Kittner Eye Center and distance from residence to interstate access. Corrective procedures, visual acuity, appointment cancellations, no-shows, and insurance data were recorded. Means were compared using 2-tailed Student t-test, Pearson χ, analysis of variance, and multivariate logistical regression determined odds ratios for loss to follow-up.In total, 199 patients met all inclusion criteria. Six-month postoperatively, patients50 miles from clinic had greater odds of loss to follow-up compared with patients25 miles (odds ratios, 3.47; 95% confidence interval, 1.24-4.12; P0.05). Patients50 miles from clinic had significantly more missed appointments than patients 25 to 50 miles away, and patients25 miles away (P=0.008). Patients20 miles from interstate access had greater loss to follow-up than those10 miles (t(150)=2.05; P0.05). Mean distance from clinic was 12.59 miles farther for patients lost to follow-up (t(197)=3.29; P0.01). Patients with Medicaid coverage had more missed appointments than those with Medicare plans (t(144)=-2.193; P0.05).Increased distance from clinic and interstate access are associated with increased missed appointments and loss to follow-up. Glaucoma specialists should consider these factors when choosing surgical interventions requiring frequent postoperative evaluations.

Osteogenesis in human arterial smooth muscle cell (HASMC) is a key feature of uremic vascular calcification (UVC). Concerning pro-oxidant properties of p-cresyl sulfate (PCS), the therapeutic effect of reactive oxygen species (ROS) scavenger on PCS triggered inflammatory signaling transduction in osteogenesis was investigated in this translational research. Based on severity level of chronic kidney disease (CKD), arterial specimens with immunohistochemistry stain were quantitatively analyzed for UVC, oxidative injury and osteogenesis along with PCS concentrations. To mimic human UVC, HASMC model was used to explore whether PCS-induced ROS could trigger mitogen-activated protein kinase (MAPK) pathways with nuclear factor-κB (NF-κB) translocation that drive context-specific gene/protein expression, including Runt-related transcription factor 2 (Runx2) and alkaline phosphatase (ALP). In parallel with PCS accumulation, CKD arteries corresponded with UVC severity, oxidative DNA damage (8-hydroxy-2′-deoxyguanosine), Runx2 and ALP. PCS directly phosphorylated extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK)/P38 (pERK/pJNK/pP38) and modulated NF-κB translocation to promote expressions of Runx2 and ALP in HASMC. Notably, intracellular ROS scavenger attenuated pERK signaling cascade and downstream osteogenic differentiation. Collectively, our data demonstrate PCS induces osteogenesis through triggering intracellular ROS, pERK/pJNK/pP38 MAPK pathways and NF-κB translocation to drive Runx2 and ALP expressions, culminating in UVC. Beyond mineral dysregulation, osteocytic conversion in HASMC could be the stimulation of PCS. Thus PCS may act as a pro-osteogenic and pro-calcific toxin. From the perspective of translational medicine, PCS and intracellular ROS could serve as potential therapeutic targets for UVC in CKD patients.

BackgroundThe objective of this study was to evaluate the clinical effect and correlation between preoperative imaging parameters and the clinical effect of endoscopic transforaminal decompression for lumbar spinal stenosis.MethodsIn this prospective study, 87 patients from Shanxi Province People’s Hospital met the criteria for lumbar spinal stenosis and were recruited from June 2014 to January 2016. These patients underwent endoscopic transforaminal decompression. The clinical symptoms were evaluated by VAS, ODI, and claudication at 3 and 6 months after surgery. The overall clinical efficacy was evaluated using the MacNab score. Yellow ligament thickness and area of the dural sac were examined by MRI. Bony vertebral canal area, real spinal canal area, nerve root canal bony area, nerve root canal real area, distance between the articular joints, and vertebral canal sagittal diameter were examined by CT. The soft tissue invasion ratio of the vertebral canal and the invasion ratio of the nerve root canal were calculated. Correlations between imaging parameters and age, sex, and clinical efficacy were examined.ResultsThe MacNab scores were excellent in 47% of cases, good in 34%, generally good in 8%, and poor in 11%. VAS, ODI, and claudication were significantly improved compared with the preoperative values (P P ConclusionTreatment of lumbar spinal stenosis by endoscopic transforaminal decompression can achieve good clinical results. This operation is less effective in patients older than 71 years of age. There were positive correlations between clinical efficacy and the vertebral canal sagittal diameter, the articular joints, soft tissue invasion ratio of the vertebral canal, and invasion ratio of the nerve root canal.

Background A decreased capacity to self-manage medications results in nonadherence, medication errors, and drug-related problems in older adults. Previous research identified 80 electronic medication adherence products available to assist patients with self-management of medications. Unfortunately, the usability and workload of these products are unknown. Objective This study aimed to examine the usability and workload of a sample of electronic medication adherence products. Methods In a prospective, mixed methods study, a sample of older adults, health care professionals, and caregivers tested the usability and workload of 21 electronic medication adherence products. Each participant tested 5 products, one at a time, after which they completed the system usability scale (SUS) and NASA-task load index (NASA-TLX), instruments that measure the usability and workload involved in using a product. Higher SUS scores indicate more user-friendliness, whereas lower NASA-TLX raw scores indicate less workload when using a product. Results Electronic medication adherence products required a mean of 12.7 steps (range 5-20) for the appropriate use and took, on average, 15.19 min to complete the setup tasks (range 1-56). Participants were able to complete all steps without assistance 55.3% of the time (103 out of the 186 tests were completed by 39 participants; range 0%-100%). The mean SUS and NASA-TLX raw scores were 52.8 (SD 28.7; range 0-100) and 50.0 (SD 25.7; range 4.2-99.2), respectively, revealing significant variability among the electronic medication adherence products. The most user-friendly products were found to be TimerCap travel size (mean 78.67, SD 15.57; P=.03) and eNNOVEA Weekly Planner with Advanced Auto Reminder (mean 78.13, SD 14.13; P=.049) as compared with MedReady 1700 automated medication dispenser (mean 28.63, SD 21.24). Similarly, MedReady (72.92, SD 18.69) was found to be significantly more work intensive when compared with TimerCap (29.35, SD 20.35; P=.03), e-pill MedGlider home medication management system (28.43, SD 20.80; P=.02), and eNNOVEA (28.65, SD 14.97; P=.03). The e-pill MedTime Station automatic pill dispenser with tipper (71.77, SD 21.98) had significantly more workload than TimerCap (P=.04), MedGlider (P=.03), and eNNOVEA (P=.04). Conclusions This study demonstrated that variability exists in the usability and workload of different electronic medication adherence products among older adults, caregivers, and clinicians. With few studies having investigated the usability and workload of electronic medication adherence products, no benchmarks exist to compare the usability and workload of these products. However, our study highlights the need to assess the usability and workload of different products marketed to assist with medication taking and provides guidance to clinicians regarding electronic medication adherence product recommendations for their patients. Future development of electronic medication adherence products should ensure that the target populations of patients are able to use these products adequately to improve medication management.

The optimal way to treat severe thoracic scoliosis remains controversial. Compared with conventional procedures, the uniportal video-assisted thoracoscopic surgery (UniVATS) rises in popularity in thoracic surgery because of less pain and faster recovery. This retrospective study aimed to apply UniVATS to treat severe thoracic scoliosis. Between October 2013 and March 2018, eight scoliotic patients with extremely large Cobb angle and profoundly limited flexibility underwent UniVATS for anterior release, followed by posterior instrumentation and fusion. The mean age at the time of surgery was 14.8 ± 2.4 years and the mean follow-up was 2.2 ± 1.3 years. The average levels of anterior thoracic discectomy and posterior fusion were 3.6 ± 0.7 and 11.5 ± 1.2, respectively. The mean coronal and sagittal correction rates were 70 ± 19% and 71 ± 23%, respectively. UniVATS contributed to minor access trauma (3-cm incision) with minimal blood loss, shorter operation time (75 ± 13 mins), less requirement of stay in the intensive care unit (0.3 ± 0.5 day) or chest tube placement (0.3 ± 0.7 day), speedier and narcotic-free recovery, and earlier ambulation within one day. This is the first study to assess the safety and efficacy of UniVATS in the treatment of severely stiff thoracic scoliosis, providing comparable surgical outcomes, less pain, faster recovery and superior cosmetic results without significant complications.

Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder resulting from dysregulated clonal proliferation of Langerhans cells. Reticulohistiocytosis (RH) is another rare histiocytosis caused by the proliferation of histiocytes other than Langerhans cells. Co-existence of LCH and RH in different organs and in the same skin area has not been reported. We present the case of a 20-year-old woman who initially had co-existing bone LCH and cutaneous RH. After 1 year of chemotherapy with cytarabine, bone LCH significantly improved but cutaneous LCH developed in the same area where cutaneous RH was, resulting in hybrid LCH and RH of the skin. This unique history provides some evidence to support the theory that LCH and RH originate from the same stem cells and subsequently develop into hybrid LCH and RH of the skin in a cytokine environment influenced by chemotherapy. Repeat skin biopsies may be considered for adjusting treatment regimens in LCH patients whenever pre-existing skin lesions progress.

OBJECTIVES: (1) Compare family decision-makers’ perceptions of quality of communication with nursing home (NH) staff (nurses and social workers) and clinicians (physicians and other advanced practitioners) for persons with advanced dementia; (2) determine the extent to which characteristics of NH residents and family decision-makers are associated with those perceptions. DESIGN: Secondary analysis of baseline data from a cluster randomized trial of the Goals of Care intervention. SETTING: Twenty-two NHs in North Carolina. PARTICIPANTS: Family decision-makers of NH residents with advanced dementia (N=302). MEASUREMENTS: During the baseline interviews, family decision-makers rated the quality of general communication and communication specific to end-of-life care using the Quality of Communication Questionnaire (QoC). QoC item scores ranged 0 – 10, with higher scores indicating better quality of communication. Linear models were used to compare QoC by NH provider type, and to test for associations of QoC with resident and family characteristics. RESULTS: Family decision-makers rated the QoC with NH staff higher than NH clinicians, including average overall QoC scores [5.5 (1.7) vs. 3.7 (3.0), p

Tick-borne diseases are a growing threat to public health in the United States, especially among outdoor workers who experience high occupational exposure to ticks. Long-lasting permethrin-impregnated clothing has demonstrated high initial protection against bites from blacklegged ticks, Ixodes scapularis Say (Acari: Ixodidae), in laboratory settings, and sustained protection against bites from the lone star tick, Amblyomma americanum (L.) (Acari: Ixodidae), in field tests. However, long-lasting permethrin impregnation of clothing has not been field tested among outdoor workers who are frequently exposed to blacklegged ticks. We conducted a 2-yr randomized, placebo-controlled, double-blinded trial among 82 outdoor workers in Rhode Island and southern Massachusetts. Participants in the treatment arm wore factory-impregnated permethrin clothing, and the control group wore sham-treated clothing. Outdoor working hours, tick encounters, and bites were recorded weekly to assess protective effectiveness of long-lasting permethrin-impregnated garments. Factory-impregnated clothing significantly reduced tick bites by 65% in the first study year and by 50% in the second year for a 2-yr protective effect of 58%. No significant difference in other tick bite prevention method utilization occurred between treatment and control groups, and no treatment-related adverse outcomes were reported. Factory permethrin impregnation of clothing is safe and effective for the prevention of tick bites among outdoor workers whose primary exposure is to blacklegged ticks in the northeastern United States.

Background Using next-generation sequencing (NGS) in newborn screening (NBS) could expand the number of genetic conditions detected pre-symptomatically, simultaneously challenging current precedents, raising ethical concerns, and extending the role of parental decision-making in NBS. The NC NEXUS (Newborn Exome Sequencing for Universal Screening) study seeks to assess the technical possibilities and limitations of NGS-NBS, devise and evaluate a framework to convey various types of genetic information, and develop best practices for incorporating NGS-NBS into clinical care. The study is enrolling both a healthy cohort and a cohort diagnosed with known disorders identified through recent routine NBS. It uses a novel age-based metric to categorize a priori the large amount of data generated by NGS-NBS and interactive online decision aids to guide parental decision-making. Primary outcomes include: (1) assessment of NGS-NBS sensitivity, (2) decision regret, and (3) parental decision-making about NGS-NBS, and, for parents randomized to have the option of requesting them, additional findings (diagnosed and healthy cohorts). Secondary outcomes assess parents’ reactions to the study and to decision-making. Methods/design Participants are parents and children in a well-child cohort recruited from a prenatal clinic and a diagnosed cohort recruited from pediatric clinics that treat children with disorders diagnosed through traditional NBS (goal of 200 children in each cohort). In phase 1, all parent participants use an online decision aid to decide whether to accept NGS-NBS for their child and provide consent for NGS-NBS. In phase 2, parents who consent to NGS-NBS are randomized to a decision arm or control arm (2:1 allocation) and learn their child’s NGS-NBS results, which include conditions from standard (non-NGS) NBS plus other highly actionable childhood-onset conditions. Parents in the decision arm use a second decision aid to make decisions about additional results from their child’s sequencing. In phase 3, decision arm participants learn additional results they have requested. Online questionnaires are administered at up to five time points. Discussion NC NEXUS will use a rigorous interdisciplinary approach designed to collect rich data to inform policy, practice, and future research. Trial registration clinicaltrials.gov, NCT02826694. Registered on 11 July, 2016. Electronic supplementary material The online version of this article (10.1186/s13063-018-2686-4) contains supplementary material, which is available to authorized users.

Background and Objective Breast density at mammography has been used as markers of breast cancer risk. However, newly introduced tomosynthesis and computer-aided quantitative method could provide more reliable breast density evaluation. Methods In the experiment, 98 tomosynthesis image volumes were obtained from 98 women. For each case, an automatic skin removal was used and followed by a fuzzy c-mean (FCM) classifier which separated the fibroglandular tissues from other tissues in breast area. Finally, percent of breast density and breast volume were calculated and the results were compared with MRI. In addition, the percent of breast density and breast area of digital mammography calculated using the software Cumulus (University of Toronto, Toronto, ON, Canada.) were also compared with 3-D modalities. Results Percent of breast density and breast volume, which were computed from tomosynthesis, MRI and digital mammography were 17.37% ± 4.39% and 607.12 cm3 ± 323.01 cm3, 20.3% ± 8.6% and 537.59 cm3 ± 287.74 cm3, and 12.03% ± 4.08%, respectively. There were significant correlations on breast density as well as volume between tomosynthesis and MRI (R = 0.482 and R = 0.805), tomosynthesis and breast density with breast area of digital mammography (R = 0.789 and R = 0.877), and MRI and breast density with breast area of digital mammography (R = 0.482 and R = 0.857) (all P values Conclusions Breast density and breast volume evaluated from tomosynthesis, MRI and breast density and breast area of digital mammographic images have significant correlations and indicate that tomosynthesis could provide useful 3-D information on breast density through proposed method.