Serum triiodothyronine-to-thyroxine (T3/T4) ratio predicts therapeutic outcome to biological therapies in elderly IBD patients.
Rates of elderly patients with inflammatory bowel diseases (IBDs) are increasing, and biomarkers are needed to optimise their therapies. Serum triiodothyronine-to-thyroxine (T3/T4) ratio has been correlated with geriatric patient frailty. To assess the suitability of T3/T4 ratio as a response marker to biologics in elderly patients with IBD. Patients with IBD over 60 years old were enrolled, when starting biological therapy. Therapeutic outcome was assessed after 54 weeks of treatment as mucosal healing (Mayo endoscopic score < 2 for ulcerative colitis; ulcer disappearance for Crohn's disease) and clinical remission (Partial Mayo Score < 2 for ulcerative colitis; Harvey-Bradshaw Index < 5 for Crohn's disease). T3/T4 ratio was evaluated at baseline, and its association with therapeutic outcomes was tested by multivariable logistic regression and receiver operating characteristic (ROC). We enrolled 80 patients; 44 achieved clinical remission and 36 mucosal healing. Baseline T3/T4 ratio was higher in patients with mucosal healing, as compared with those without mucosal healing (P < 0.0001), regardless of the disease type or biological drug (OR 6.4 [2.9-14.3] for each T3/T4 unit increase, P < 0.0001). A cut point of 3.3 was identified as the optimal threshold of baseline T3/T4 ratio for predicting mucosal healing, providing 78% sensitivity and 89% specificity (area under the ROC curve 0.88 [0.79-0.94]; positive and negative likelihood ratios 6.8 [2.9-15.9] and 0.3 [0.1-0.5] respectively). T3/T4 ratio seems a reliable tool for predicting therapeutic outcome of biological therapy in elderly patients with IBD. If validated, the assessment of this parameter before starting biological treatment might be suggested.


Developmental dissociation of serotonin-induced spike broadening and synaptic facilitation in Aplysia sensory neurons.
In sensory neurons (SNs) of adult Aplysia, serotonin (5-HT)-induced spike broadening has long been implicated as important for synaptic facilitation [spike duration-dependent (SDD) facilitation], particularly at nondepressed synapses. At depressed synapses, spike broadening has less impact on synaptic facilitation; under these conditions, 5-HT induces a spike duration-independent (SDI) form of facilitation (). It has been difficult to dissociate clearly the cellular mechanisms underlying these two forms of facilitation. However, the observation that a major form of spike broadening emerges late in juvenile development () provides a unique opportunity to examine the relationship between spike broadening and synaptic facilitation in juvenile Aplysia. We have identified three forms of synaptic plasticity in juvenile Aplysia: homosynaptic depression, SDD facilitation, and SDI facilitation. We show that homosynaptic depression is fully developed in the juvenile and that 5-HT reliably induces synaptic facilitation at depressed synapses. However, in nondepressed synapses, 5-HT-induced facilitation is not reliable. Further analysis revealed that the relationship between spike broadening and synaptic facilitation for nondepressed synapses is the inverse of that in adults. Surprisingly, in juveniles, minor spike broadening induced by 5-HT results in significant synaptic facilitation, whereas major spike broadening, when it occurs, does not. These results suggest a model in which juvenile synapses predominantly use SDI facilitation, and with the emergence of major spike broadening, a developmentally transient inhibitory process emerges. This inhibitory process seems to be independent of major spike broadening induced by 5-HT because directly broadening the spike with 4-aminopyridine induces adult-like SDD synaptic facilitation. Finally, in the adult, the inhibitory process is either lost or masked, and SDD facilitation predominates at nondepressed synapses.


Complexes With Biologically Active Ligands. Part 10 Inhibition of Carbonic Anhydrase Isozymes I and II With Metal Complexes of Imidazo[2,1-b ]-1,3,4-Thiadiazole-2-Sulfonamide.
THE TITLE COMPOUND WAS PREPARED BY AN IMPROVED VARIANT OF THE LITERATURE PROCEDURE, AND METAL COMPLEXES CONTAINING ITS ANION AND THE FOLLOWING METAL IONS: Zn(II), Cd(II), Hg(II), Co(II), Ni(II), Cu(II), V(IV), Fe(III) and Ag(I) were synthesized and characterized by standard procedures (elemental analysis; IR, electronic, NMR and EPR spectroscopy; TG, magnetic and conductimetric measurements). The parent sulfonamide and its metal complexes are potent inhibitors of two carbonic anhydrase (CA) isozymes, CA I and II, and they might possess applications as selective cerebrovasodilating agents.


Acute exercise modulates the inflammatory response in adipose tissue in both lean and obese mice.
Acute physical exercise acts as a metabolic stressor, promoting activation of the immune system, and this response could be relevant in the adipose tissue remodeling process. In addition, some cytokines have important functions in lipolysis. Because chronic exercise improves obesity-related metabolic and inflammatory dysfunction, herein we investigated the effect of acute exercise on the inflammatory responses in the adipose tissues of lean and obese mice. Lean mice were fed a standard chow diet, whereas obese mice were fed a high-refined carbohydrate diet for 8 wk. Both groups were subjected to 60 min of moderate-intensity exercise. In the epididymal adipose tissue of lean mice, exercise enhanced interleukin (IL)-6 and tumor necrosis factor-α levels, which correlated positively with increased serum free fatty acid concentrations. In vivo confocal imaging of epididymal adipose tissue vessels revealed higher recruitment of neutrophils after exercise. Also, the number of leukocytes expressing CD11b+F480- was elevated 6 h after exercise. Similarly, the chemokine (C-X-C motif) ligand 1 level increased at 6 h and remained high until 24 h after exercise. Myeloperoxidase activity was increased at 6, 12, and 24 h after exercise. Surprisingly, however, no changes were observed in epididymal adipose tissue from obese mice, considering proinflammatory cytokines (IL-6 and tumor necrosis factor-α). On the other hand, IL-13, IL-4, and IL-10 levels were higher in obese mice after exercise. These data suggest that acute exercise promotes an inflammatory response in the adipose tissue of lean mice that is observed as part of its role in adipose tissue remodeling. In contrast, acute exercise promotes an antiinflammatory response in adipose tissue from obese mice, likely as an important tool for restoring homeostasis.


Using personalized medicine in gliomas: a genomic approach to diagnosis and overcoming treatment resistance in a case with pleomorphic xanthoastrocytoma.
A patient who was initially considered to have a glioblastoma (GBM) had molecular analysis, showing that it was a pleomorphic xanthoastrocytoma (PXA). Up to 78% of PXA tumors have BRAF V600E mutations. Primary brain tumors with BRAF mutations can have a good response to BRAF MEK inhibitors (BRAF MEKi), and there may be a synergistic response when combined with autophagy inhibitors. A 20-year-old man found to have a large brain mass with midline shift underwent resection. He was diagnosed with "GBM" and treated with radiation and temozolomide with subsequent disease recurrence. Review of histology showed malignant PXA with BRAF V600E mutation. Treatment with Dabrafenib and Trametinib was started, and tumor size increased in size after 14 months of treatment. Given studies showing that resistance to BRAF inhibition can be overcome by autophagy inhibition, chloroquine was added. Patient has been on "triple" therapy for 15 months and has radiographically Stable Disease. At MCC, 3% of patients with gliomas have BRAF mutations who could potentially benefit from this combination therapy. This is the first report of a PXA patient receiving therapy with BRAF MEKi and an autophagy inhibitor with prolonged stable disease. This patient highlights the importance of a molecular interrogation in gliomas to provide an integrated diagnosis and effective treatment. This may be useful in up to 3% of glioma patients with BRAF mutations. Molecular testing in neuro-oncology is providing new avenues of diagnosis and treatment, and detailed molecular interrogation should be considered routine.


Superiority of 68Ga-FAPI-04 in Delineation of Soft Tissue and Liver Metastases in Chromophobe Renal Cell Carcinoma for Restaging.
Chromophobe renal cell carcinoma (RCC) is a rare tumor. We described findings of 18F-FDG PET/CT and 68Ga-FAPI-04 PET/CT of metastatic chromophobe RCC in a 56-year-old woman. 68Ga-FAPI-04 PET/CT demonstrated that the metastatic lesions in the liver, left posterior abdominal wall, and the left waist had intense uptake of 68Ga-FAPI-04, which was higher than that of 18F-FDG on 18F-FDG PET/CT. 68Ga-FAPI-04 PET/CT also delineated the metastatic lesions more clearly than 18F-FDG PET/CT. This case highlights 68Ga-FAPI-04 PET/CT may be promising in restaging of chromophobe RCC.


Comparison of Serum Thyroglobulin Levels in Differentiated Thyroid Cancer Patients Using In-House Developed Radioimmunoassay and Immunoradiometric Procedures.
Thyroglobulin (Tg) is a proven tumor marker in the follow-up and post-operative management of patients with differentiated thyroid cancer (DTC). All assays for serum thyroglobulin (s-Tg) are based on immunoassays, however, the assay technique has a bearing on the variations seen in the estimations. We studied this using four in-house developed radioimmunoassays (RIA) and immunoradiometric assays (IRMA). Limit of detection, working range, recovery, dilution test, precision profiles and method comparison were evaluated. All four methods were used for the estimation of s-Tg in DTC patients and also compared for their performance using commercially available Tg IRMA kits from DiaSorin and Izotop. The s-Tg values measured by six different immunoassays showed very significant inter-method correlation (0.84-0.99, p < 0.001). However, among the in-house developed assays; the coated tube IRMA showed a better sensitivity and precision at the lower concentration range and hence, is preferable for the routine measurement of s-Tg in patients negative for Tg autoantibodies (TgAb). Although the second generation IRMAs offer practical benefits of having higher sensitivity, shorter turn-around time and convenience of automation, they, unfortunately, also have higher tendency for interference from both TgAb and heterophilic antibodies, if present in the sample. On the contrary, RIA is less prone to such interference and, hence, can be used in patients with TgAb. In order to effectively use this test, it is important that nuclear medicine physicians and endocrinologists understand these intrinsic technical limitations encountered during s-Tg measurement.


Rare crystalline nephropathy leading to acute graft dysfunction: a case report.
Adenine phosphoribosyl transferase (APRT) deficiency is a rare genetic form of kidney stones and/or kidney failure characterized by intratubular precipitation of 2,8 dihydroxyadenine crystals. Early diagnosis and prompt management can completely reverse the kidney injury. 44 year old Indian male, renal transplant recipient got admitted with acute graft dysfunction. Graft biopsy showed light brown refractile intratubular crystals with surrounding giant cell reaction, consistent with APRT deficiency. Patient improved after receiving allopurinol and hydration. APRT forms a reversible cause of crystalline nephropathy. High index of suspicion is required for the correct diagnosis as timely diagnosis has therapeutic implications.


Effects of ethnic enclosure of neighborhoods, workplace, and industrial sectors on earnings.
In this study, we extend prior work on how ethnic boundaries in specific contexts affect the earnings of racial and ethnic groups by simultaneously exploring how levels of ethnic enclosure, measured by co-ethnic concentration, of neighborhoods, workplaces, and industrial sectors, and their "moderating" effects on the earnings of six major recent racial and ethnic immigrant groups in the eight largest Canadian cities. The consideration of ethnic boundaries in multiple contexts portrays a more realistic picture of the effect of ethnic boundaries on earnings. The study helps us to understand how ethnic enclosure in various contexts affects the economic attainments of groups with higher proportions of immigrants. The study is based on 2006 Canadian census data. The findings show that most members of the six included racial/ethnic minority groups live and work in environments with high levels of ethnic enclosure. Besides, in general, the earnings of employees are negatively related to co-ethnic concentration in neighborhood and workplace, while the relationship with industrial co-ethnic concentration is not consistent. The earnings of employers are negatively related to co-ethnic concentration in the workplace only. The moderating effects of various co-ethnic contexts on earnings are mostly positive for both employers and employees, although they are more likely to be significant among employees. In addition, the findings show variations among the six groups.


Immunogenicity and tolerability of a bivalent virus-like particle norovirus vaccine candidate in children from 6 months up to 4 years of age: A phase 2 randomized, double-blind trial.
We conducted a dose-finding phase 2 study of the HilleVax bivalent virus-like particle (VLP) vaccine candidate (HIL-214) in two cohorts of children, 6-≤12 months and 1-≤4 years of age (N = 120 per cohort), in Panama and Colombia (ClinicalTrials.gov, identifier NCT02153112). On Day 1, children randomized to one of the four equal groups received intramuscular injections of four different HIL-214 formulations containing 15/15, 15/50, 50/50, or 50/150 μg of GI.1/GII.4c genotype VLPs and 0.5 mg Al(OH)3. On Day 29, half the children in each group received a second vaccination (N = 60), while the other half received saline placebo injections to maintain the blind. VLP-specific ELISA Pan-Ig and histo-blood group binding antigen-blocking antibodies (HBGA) were measured on Days 1, 29, 57 and 210. On Day 29, after one dose, there were large Pan-Ig and HBGA responses in both age cohorts with some indication of dose-dependence, and higher geometric mean titers (GMT) in the older children. A further increase in titers was observed 28 days after a second dose in the 6-≤12-month-old groups, but less so in the 1-≤4-year-old groups; GMTs at Day 57 were broadly similar across doses and in both age groups. GMTs of Pan-Ig and HBGA persisted above baseline up to Day 210. All formulations were well tolerated with mostly mild-to-moderate transient solicited adverse events reported by parents/guardians, and no vaccine-related serious adverse events occurred. Further development of HIL-214 is warranted to protect the most susceptible young children against norovirus.


Spouse encouragement of self-reliance and other-reliance in rheumatoid arthritis couples.
Studying and helping couples burdened with a major life stressor such as rheumatoid arthritis (RA) can be enhanced by employing well-understood conceptual and empirical frameworks, in our research person/environment fit (P x E) models. We measured P x E effects in a sample of 62 rheumatoid arthritis (RA) patients with locus of control beliefs, age, and the health status of the subjects as the Person variables and their spouses' control encouragement as the Environment variable. As predicted, externals were most sensitive to their spouses' behavior. Health status and age moderated the effects of the subjects' control beliefs and spouses' control efforts. Control encouragement showed positive benefits, but only for the younger and healthier subjects; it was related to increased psychological distress for externals in poorer health. Although many models of therapy suggest the benefits of increasing personal control, these data suggest the necessity of employing a more complex model integrating both person and social environment variables in understanding mental health.


Negative charge at the protein kinase CK2 site enhances recognition of the SV40 large T-antigen NLS by importin: effect of conformation.
SV40 large tumor-antigen (T-ag) nuclear import is enhanced by the protein kinase CK2 (CK2) site (Ser111Ser112) flanking the nuclear localization sequence (NLS). Here we use site-directed mutagenesis to examine the influence of negative charge and conformation at the site on T-ag nuclear import and recognition by the NLS-binding importin subunits. Negative charge through aspartic acid in place of Ser111 simulated CK2 phosphorylation in enhancing nuclear accumulation to levels well above those of proteins lacking a functional CK2 site. This was shown to be through enhancement of T-ag NLS recognition by importin using an ELISA-based assay. Asp112-substituted mutants containing proline at positions 109, 110 (wild-type position) or 111 were compared to assess the role of conformation at the CK2 site. Maximal nuclear import of the protein with Pro109 was lower than that of the Pro110 derivative, with the Pro111 variant even lower, these differences also being attributable to effects on importin binding. All results indicate a correlation of the initial nuclear import rate with the importin binding affinity, demonstrating that NLS recognition by importin is a key rate-determining step in nuclear import.


Auditing the effect of experience and change on home parenteral nutrition related complications.
A prospective record of all patients receiving home parenteral nutrition (HPN) in Tayside since 1980 has been used to audit the effect of experience and specific policy changes on HPN related complications. Total HPN related complications fell significantly over the years from 1.59 complications per treatment year during the initial 5 years of HPN experience to the current rate of 0.36 complications per treatment year. Specific policy changes, such as modification of the glucose concentration of feed, could also be shown to produce a significant benefit in the reduction of complications. Increasing experience with HPN results in a fall in complication rates, however, continuous audit of HPN is essential to determine the effect of policy changes on complication rates.


Temporal dependence Mahalanobis distance for anomaly detection in multivariate spacecraft telemetry series.
Spacecraft telemetry data are real-time data as the only basis for ground operation station and management system to judge the working performance and health status of spacecrafts in orbit. Telemetry data are high dimension, strong-dependent, and pseudo-periodic series, which bring great challenges to traditional anomaly detection methods of multivariate parameters. In this case, with the advantages of strong feature extraction and space injection ability, Mahalanobis distance (MD)-based approach has been a strong foundation for industrial system health monitoring. However, the typical MD-based method performs anomaly detection with a fixed threshold for MD series without capturing temporal evolution which cause high false alarms or missing alarms for complex abnormal modes. In this work, the temporal dependence Mahalanobis distance (TDMD) is realized based on multi-factors prediction which can effectively detect contextual and collective anomalies in multivariate telemetry series. Upper and lower limits with time series correlation and dynamic characteristics for the MD of each arriving multivariate point are constructed for online testing. Adequate experiments on simulated and real telemetry series verify the effectiveness and applicability of the proposed method.


Anti-tumor effects and cell motility inhibition of the DN604-gemcitabine combined treatment in human bladder cancer models.
Bladder cancer is one of the major tumors for men in the world, in which therapy the combination of cisplatin and gemcitabine is still fist-line applied to treat with advanced or metastatic bladder cancer. In our early study, we developed a potential Pt(II) agent, DN604, which has anti-tumor effect as potent as cisplatin toward bladder cancers. Herein, we aim at investigating the combinatory application of DN604 with gemcitabine for bladder cancer treatment. In vitro studies proved that the combined treatment of DN604 and gemcitabine could limit cell proliferation by elevating the incidence of DNA damage induced apoptosis. Notably, further researches showed that the DN604-gemcitabine treatment suppressed cell autophagy to inhibit cell motility upon the ROS dependent p38 MAPK signaling pathway, explicating its better anti-tumor activity than single drug treatment or the cisplatin-gemcitabine treatment. In vivo tests confirmed that the DN604-gemcitabine treatment has superior anti-tumor activity with low toxicity to cisplatin or its combination with gemcitabine treatments. DN604 plus gemcitabine, is of great significance for the treatment with human bladder cancer. Our study has provided a potential combination treatment option.


Conditional reprogramming of pediatric airway epithelial cells: A new human model to investigate early-life respiratory disorders.
Airway epithelial cells (AEC) are quite difficult to access in newborns and infants. It is critically important to develop robust life-extended models to conduct translational studies in this age group. We propose the use of a recently described cell culture technology (conditionally reprogrammed cells-CRC) to generate continuous primary cell cultures from nasal and bronchial AEC of young children. We collected nasal and/or bronchial AEC from a total of 23 subjects of different ages including newborns/infants/toddlers (0-2 years; N = 9), school-age children (4-11 years; N = 6), and a group of adolescent/adult donors (N = 8). For CRC generation, we used conditioned medium from mitotically inactivated 3T3 fibroblasts and Rho-associated kinase (ROCK) inhibitor (Y-27632). Antiviral immune responses were studied using 25 key antiviral genes and protein production of type III epithelial interferon (IFN λ1) after double-stranded (ds) RNA exposure. CRC derived from primary AEC of neonates/infants and young children exhibited: (i) augmented proliferative capacity and life extension, (ii) preserved airway epithelial phenotype after multiple passages, (iii) robust immune responses characterized by the expression of innate antiviral genes and parallel nasal/bronchial production of IFN λ1 after exposure to dsRNA, and (iv) induction of airway epithelial inflammatory and remodeling responses to dsRNA (eg, CXCL8 and MMP9). Conditional reprogramming of AEC from young children is a feasible and powerful translational approach to investigate early-life airway epithelial immune responses in humans.


Attenuated total reflection micro FTIR characterisation of pigment-binder interaction in reconstructed paint films.
The interaction of pigments and binding media may result in the production of metal soaps on the surface of paintings which modifies their visible appearance and state of conservation. To characterise more fully the metal soaps found on paintings, several historically accurate oil and egg yolk tempera paint reconstructions made with different pigments and naturally aged for 10 years were submitted to attenuated total reflectance Fourier transform infrared (ATR FTIR) microspectroscopic analyses. Standard metal palmitates were synthesised and their ATR spectra recorded in order to help the identification of metal soaps. Among the different lead-based pigments, red lead and litharge seemed to produce a larger amount of carboxylates compared with lead white, Naples yellow and lead tin yellow paints. Oil and egg tempera litharge and red lead paints appeared to be degraded into lead carbonate, a phenomenon which has been observed for the first time. The formation of metal soaps was confirmed on both oil and egg tempera paints based on zinc, manganese and copper and in particular on azurite paints. ATR mapping analyses showed how the areas where copper carboxylates were present coincided with those in which azurite was converted into malachite. Furthermore, the key role played by manganese in the production of metals soaps on burnt and raw sienna and burnt and raw umber paints has been observed for the first time. The formation of copper, lead, manganese, cadmium and zinc metal soaps was also identified on egg tempera paint reconstructions even though, in this case, the overlapping of the spectral region of the amide II band with that of metal carboxylates made their identification difficult.


Prevalence and factors associated with fatigue in patients with ulcerative colitis in China: a cross-sectional study.
Fatigue is one of the most common symptoms reported by patients with ulcerative colitis (UC), while it has not been fully recognized and taken seriously in clinical practice. We aimed to investigate the prevalence of fatigue in patients with UC and identify the factors associated with fatigue and its severity in China. A cross-sectional study was conducted in Affiliated Hospital of Nanjing University of Chinese Medicine from May 2020 to February 2021. Demographic and clinical characteristics were collected. Fatigue was evaluated with the Fatigue Severity Scale and the Multidimensional Fatigue Inventory. The Hospital Anxiety and Depression Scale, the Pittsburgh Sleep Index Scale and the Malnutrition Universal Screening Tool were respectively used to evaluate the anxiety, depression, sleep disturbance and nutritional risk of patients with UC. A total of 220 UC patients were enrolled in this study. The prevalence of fatigue in patients was 61.8%, of which in patients with disease activity was 68.2%, and in patients in remission was 40.0%. Univariate analysis indicated that the Montreal classification, disease activity, anemia, anxiety, depression, sleep disturbance and high nutritional risk were the factors associated with fatigue in Patients with UC. Multivariate logistic regression analysis showed that the Montreal classification (E3: E1, OR = 2.665, 95% CI = 1.134-6.216), disease activity (OR = 2.157, 95% CI = 1.055-4.410) and anxiety (OR = 2.867, 95% CI = 1.154-7.126) were related to an increased risk of fatigue. Disease activity (RC = 0.240, 95% CI = 0.193-0.674) and anxiety (RC = 0.181, 95% CI = 0.000-0.151) were associated with severity of fatigue. This study demonstrated that the prevalence of fatigue among UC patients in China. The Montreal classification, disease activity and anxiety are associated with an increased risk of fatigue.


Traumatic eye and intracranial air-movement from a subconjunctival to an intracranial position.
In a 12-year-old boy, air accidentally introduced subconjunctivally from the pointed tip of an air compressor hose, moved to an intracranial position over the sella turcica as demonstrated by x-ray films. The globe and a portion of the optic nerve were also outlined by air contrast. A minor corneal abrasion and traumatic iritis cleared promptly and no fractures or other damage occurred.


To investigate the individual and household-level factors influencing the willingness to pay for cataract surgery among patients aged 50 years and older in rural China: a cross-sectional study.
To investigate the factors influencing the willingness to pay (WTP) for cataract surgery among patients aged 50 years and older in rural China at both individual and household levels. A cross-sectional study. The study was conducted in Gansu, China. Patients aged ≥50 years who were diagnosed with cataracts indicated for surgery and lived rural in Gansu from October to December 2020 were included in the study. The main study outcome was the patients' WTP for cataract surgery. The association of individual characteristics, knowledge about cataracts, health status and household characteristics with patients' WTP was also evaluated based on the collected data using structured questionnaires. A total of 324 (85.94%) patients in the study reported that they were willing to pay for their cataract surgery. However, only 179 (47.48%) patients were willing to pay over ¥1000 to cover the cost of cataract surgery under the New Rural Cooperative Medical System (NRCMS). Patients aged 75 years and older were significantly less likely to pay for cataract surgery (p=0.037). Better visual status (p=0.032), self-reported severe poor visual status (p=0.001), higher annual household income (p=0.052) and a higher level of children's education (p=0.076) were significantly more likely to pay for cataract surgery. The WTP for cataract surgery in rural China is still insufficient. More than half of patients' WTP for surgery do not cover the cost of cataract surgery after reimbursement by the NRCMS. Both individual and household characteristics contribute to the low WTP for cataract surgery.


The use intention of hospital report cards among patients in the presence or absence of patient-reported outcomes.
So far, the adoption of hospital report cards (HRCs) falls short of expectations. One promising strategy is to modify the content of HRCs by presenting patient-reported outcomes (PROs). To identify the key determinants influencing patients to use HRCs for hospital decision making and determine the effect of presenting PROs on HRCs on their use intention. Primary survey data were collected (5/6-2021) on a sample of 2000 randomly selected insurees from a German statutory health insurance who have undergone elective hip arthroplasty surgery. Overall, 447 participants (mean age 66.56) completed the survey and were included in the analysis. Respondents rated "PROs" as most important for the hospital choice followed by "Mobility at hospital discharge" and "Confirmed diagnosis rate". Patients generally perceive HRCs to be a good idea that makes searching for a hospital more interesting. We identified attitude and social influence as the most important determinants for using HRCs (p<.001 each). The presence of PROs on HRCs was not associated with an increased intention to use HRCs neither in our descriptive analysis (p=.593), nor in our research model (p=.763). Patients value PROs to be an important information for choosing a hospital. Nevertheless, health policy makers should note that presenting PROs on HRCs as a single approach is not likely to increase the use of HRCs.


Epigenetic regulation of RET receptor tyrosine kinase and non-coding RNAs in MTC.
Medullary thyroid carcinoma (MTC) is an aggressive and rare cancer with limited treatment options for metastatic disease. Due to this, there is a need for a better understanding of MTC biology in the hope of improved treatments. One area of improved understanding of cancer biology is epigenetics. Epigenetics is defined as cellular processes which alter gene expression independent of changes in the primary DNA sequence. These processes include modifications such as DNA methylation, microRNA deregulation and post-translational histone modifications, all of which have been implicated in tumorigenesis of MTC. Transcription of the main driver of MTC - the REarranged during Transfection (RET) proto-oncogene can also be modulated by epigenetic alterations. This review will present a review of MTC and its epigenetic links with a particular focus on targeting epigenetic mechanisms as novel therapeutic strategies.


The World Congress of Paediatric Cardiology and Cardiac Surgery: a short factual history by Jane Somerville.
The World Congress of Paediatric Cardiology and Cardiac Surgery has survived with minimal assets and simple organisation. Each congress is special, taking on the humour, flavour, and culture of the organising country. It is hard work for a few organisers and money is hard to raise. The steering committee works closely, fairly, and successfully, and even though accused of being secretive and effete that does not matter. It is efficient and produces successful, happy world congresses, where all involved with the speciality are welcome. With so many "grown-ups" with congenital heart disease, it is no longer just a paediatric problem - maybe the name of this congress must change again. Regardless, the flag must fly on.


Outcomes of home parenteral nutrition in 34 patients with intestinal failure from recurrent or progressive peritoneal malignancy of gastro-intestinal tract origin.
To investigate the outcomes of 34 patients with intestinal failure secondary to advanced peritoneal malignancy on home parenteral nutrition (HPN). A retrospective analysis of all known patients receiving HPN at any time between January 2012 and the 31st March 2020 registered in a high volume peritoneal malignancy surgical centre database. The median duration of HPN for all patients was 309.5 days (range 31-2198). Overall 11/34 went on to have multivisceral transplants. Of these 5/11 resumed normal oral intake off HPN, 3 died and 3 required ongoing HPN. Average time on HPN for patients with pseudomyxoma peritonei of appendix origin was 338 days (71-2198) compared with 90 days (31-260) in the group with more aggressive tumours. HPN is feasible and effective in selected patients with pseudomyxoma peritonei as either a bridge to transplant or definitive treatment. As expected, patients with more aggressive tumours fare worse.


Survival and quality of life of patients requiring acute renal replacement therapy.
To assess long-term survival and health-related quality of life in patients with acute renal failure. Cross-sectional cohort study in the ten-bed medical-surgical intensive care unit and the three-bed acute dialysis unit in a tertiary care hospital. 703 patients receiving renal replacement therapy for acute renal failure during 1998-2002. The mortality rate was 41% at 28 days, 57% at 1 year, and 70% at 5 years. SOFA score, age, and continuous renal replacement therapy were independent predictors of 1-year mortality. The median follow-up time was 3.9 years for mortality and 2.4 years for health-related quality of life. Of the 229 survivors in 2003, 153 (67%) responded to the health-related quality of life questionnaire. Health-related quality of life was evaluated with the EuroQol (EQ-5D) instrument including a visual analogue scale (VAS) score to evaluate the patient's perceived health. The EQ-5D score was significantly lower in the study population than in the age- and gender-matched Finnish population (0.68 vs. 0.86). Median VAS scores were 69.5 and 70.0, respectively. Patients' age and duration of follow-up had no significant effect on EQ-5D or VAS scores. Mortality and EQ-5D data were used to calculate quality-adjusted life years. Quality-adjusted survival was poor (15 quality-adjusted life years per 100 patients in the first year of follow-up). The long-term survival of patients with acute renal failure is poor. Although survivors have a low health-related quality of life, they are as satisfied with their health as the general population.


Publisher Correction: The effect of attention and working memory on the estimation of elapsed time.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


The swing shift: Opportunity to enhance trauma training in Australia.
Training in trauma forms a fundamental component of general surgical training in Australia. It faces a number of challenges, including the limitations of working hours and increasing use of non-operative management techniques. Adjustment of rosters to encompass a "swing shift" (12pm-midnight) is one proposed solution to maximise exposure of junior surgical doctors to trauma. This proposal prompted a review of the timing of major trauma presentations and interventions at a Level 1 trauma centre. A retrospective observational study was performed of all major trauma presentations to Westmead Hospital, Australia over ten-years (2008-2017). Trauma operative procedures and major resuscitations were reviewed across three potential shifts: day shift (0730-1930), night shift (1930-0730) and "swing shift" (1200-midnight). Operative interventions included: laparotomy, thoracotomy/sternotomy, re-look laparotomy, rib fixation and tracheostomy. Descriptive statistics were obtained for between-shift comparisons. Over the ten-years there were 3745 full trauma team activations (FTTAs). The "swing shift" had the highest number of FTTAs, patients with injury severity scores >15, patients requiring resuscitation and emergency operations (laparotomies, sternotomies/thoracotomies). More major trauma calls, laparotomies and thoracotomies occurred during a theoretical "swing shift" rather than the standard day and night shifts. Changing trauma rostering for junior doctors to reflect this peak in clinical and operative demand could change exposure to trauma training.


[Progressive scotoma with perception of photopsia].
Acute annular outer retinopathy (AAOR) is a very rare variant of acute zonal occult outer retinopathy (AZOOR). Both variants are characterized by the perception of a progressive visual field defect and can be accompanied by photopsia. In contrast to AZOOR, a progressive whitish and annular demarcation of the involved retina is observed in AAOR using ophthalmoscopy. Optical coherence tomography (OCT) reveals morphological changes predominantly in the outer retinal layers. Although there is no proof of an effective therapy, in the case presented here further progression could be stopped by a combination of antiviral and immunosuppressive therapy.


A cross-species quantitative proteomic study of salt adaptation in a halotolerant environmental isolate using 15N metabolic labelling.
We examine differential protein expression in Euhalothece sp. BAA001, an extremely halotolerant and unsequenced cyanobacterium, under adaptation to low (0% w/v), medium (3% w/v), high (6% w/v) and very high (9% w/v) salt concentrations using cross-species protein identification tools. We combine stable isotope labelling with 1-D SDS-PAGE, and MASCOT protein identification software with MS-driven BLAST searches, to produce an accurate method for protein identification and quantitation. The use of metabolic labelling to improve the confidence in identification of proteins in cross-species proteomics is demonstrated. Three hundred and eighty-three unique proteins were identified, and 72 were deemed to be differentially expressed (average CV for quantitations was 0.10 +/- 0.08), belonging to 24 functional groups. Responses to low salt as well as high salt are discussed in terms of adaptation and evidence shows that Euhalothece cells display 'stress' responses in nonsaline conditions as well as higher salt environments.


Terahertz EPR spectroscopy using a 36-tesla high-homogeneity series-connected hybrid magnet.
Electron Paramagnetic Resonance (EPR) is a powerful technique to study materials and biological samples on an atomic scale. High-field EPR in particular enables extracting very small g-anisotropies in organic radicals and half-filled 3d and 4f metal ions such as MnII (3d5) or GdIII (4f7), and resolving EPR signals from unpaired spins with very close g-values, both of which provide high-resolution details of the local atomic environment. Before the recent commissioning of the high-homogeneity Series Connected Hybrid magnet (SCH, superconducting + resistive) at the National High Magnetic Field Laboratory (NHMFL), the highest-field, high-resolution EPR spectrometer available was limited to 25 T using a purely resistive "Keck" magnet at the NHMFL. Herein, we report the first EPR experiments performed using the SCH magnet capable of reaching the field of 36 T, corresponding to an EPR frequency of 1 THz for g = 2. The magnet's intrinsic homogeneity (25 ppm, that is 0.9 mT at 36 T over 1 cm diameter, 1 cm length cylinder) was previously established by NMR. We characterized the magnet's temporal stability (5 ppm, which is 0.2 mT at 36 T over one-minute, the typical acquisition time) using 2,2-diphenyl-1-picrylhydrazyl (DPPH). This high resolution enables resolving the weak g-anisotropy of 1,3-bis(diphenylene)-2-phenylallyl (BDPA), Δg = 2.5 × 10-4 obtained from measurements at 932 GHz and 33 T. Subsequently, we recorded EPR spectra at multiple frequencies for two GdIII complexes with potential applications as spin labels. We demonstrated a significant reduction in line broadening in Gd[DTPA], attributed to second order zero field splitting, and a resolution enhancement of g-tensor anisotropy for Gd[sTPATCN]-SL.


How Inflammasomes Inform Adaptive Immunity.
An immune response consists of a finely orchestrated interplay between initial recognition of potential microbial threats by the innate immune system and subsequent licensed adaptive immune neutralization. The initial recognition integrates environmental cues derived from pathogen-associated molecular patterns and cell-intrinsic damage-associated molecular patterns to contextualize the insult and inform a tailored adaptive response via T and B lymphocytes. While there are much data to support the role of transcriptional responses downstream of pattern recognition receptors in informing the adaptive immune response, markedly less attention has been paid to the role of post-translational responses to pathogen-associated molecular pattern and damage-associated molecular pattern recognition by the innate immune system, and how this may influence adaptive immunity. A well-characterized post-translational consequence of pattern recognition receptor signaling is the assembly of a multimeric signaling platform, termed the inflammasome, by members of the nucleotide-binding oligomerization domain (Nod), leucine-rich repeat-containing receptors (NLRs), and pyrin and HIN domain (PYHIN) families. Inflammasomes assemble in response to cytosolic perturbations, such as mitochondrial dysfunction and aberrant ion fluxes in the case of the canonical NLRP3 inflammasome or the presence of bacterial lipopolysaccharides in the case of the non-canonical inflammasome. Assembly of the inflammasome allows for the cleavage and activation of inflammatory caspases. These activated inflammatory caspases in turn cleave pro-form inflammatory cytokines into their mature bioactive species and lead to unconventional protein secretion and lytic cell death. In this review, we discuss evidence for inflammasome-mediated instruction and contextualization of infectious and sterile agents to the adaptive immune system.


White phosphorus as a ligand for the coinage metals.
Reaction of equimolar quantities of MX (M = Au, Cu, X = Cl; M = Ag, X = OTf) and GaCl(3) in CH(2)Cl(2) with P(4) leads to phosphorus ligating a cationic coinage metal centre. For Cu and Ag, ion-contacted coordination polymers are formed; for Au, an ion-separated complex is observed that features the [Au(η(2)-P(4))(2)](+) cation, which is the first homoleptic Au-P(4) complex to be characterised in the condensed phase.


Partial characterization of the adsorbed protein layer on Dirofilaria immitis (Nematoda) cuticle.
Electron microscopy coupled with ferritin-conjugated indirect immunolabeling was used to locate sites of adsorbed host protein on cuticular surfaces of the adult canine heartworm, Dirofilaria immitis. The epicuticle appeared as a trilaminated structure. At high magnifications, the outermost layer of this structure was resolved into a trilaminar layer, which might correspond to the plasma membrane of animal cells. A ruthenium red-positive layer was external to the epicuticle. Ferritin-antibody conjugates showed evidence of adsorbed dog albumin, dog immunoglobulin class G (IgG), and dog complement fraction 3 (C3) on the surface. Ferritin adsorption to control surfaces was minimal. Possible causes and effects of interfacial host-protein adsorption are discussed in an attempt to bring insight to the hemocompatible nature of the parasitic cuticle.


MHRA advises monitoring blood concentrations of clozapine and other antipsychotics.
Every month, DTB scans sources of information on treatments, disease management and other healthcare topics for key items to bring to our readers' attention and help them keep up to date. To do this, we produce succinct, contextualised summaries of the information concerned.


A high-score Mediterranean dietary pattern is associated with a reduced risk of peripheral arterial disease in Italian patients with Type 2 diabetes.
The 'Mediterranean diet' is considered to exert protective effects on cardiovascular disease, although a wide range of dietary patterns exists among subjects living even in the same Mediterranean country. To investigate the association between specific dietary patterns and peripheral arterial disease (PAD) in Italian Type 2 diabetes patients. From a cohort of 944 patients with Type 2 diabetes, 144 patients with PAD were selected, and matched for age and sex with 288 Type 2 diabetic control patients without macrovascular complications. A dietary score was elaborated from a semiquantitative food frequency questionnaire. The higher the final score, the healthier the eating habit. In multivariate analysis, a higher score was independently associated with a significant reduction in PAD risk [odds ratio (OR) = 0.44; 95% confidence interval (CI) 0.24, 0.83]. Diabetes duration (OR > 15 years = 2.49; 95% CI 1.45, 4.25), hypertension (OR = 2.12; 95% CI 1.31, 3.45) and butter consumption (OR = 2.6; 95% CI 1.15, 3.68) were also significantly associated with PAD. The dietary score significantly improved the predictive value of models based on duration of diabetes and hypertension. (LSR = 2.19, DF = 7, P < 0.001). The effect of a high dietary score on the risk of PAD was independent of diabetes duration and hypertension. In Italian Type 2 diabetics, a higher dietary score has a protective role against PAD. The use of butter increases the risk of PAD even in patients regularly consuming olive oil. Dietary advice may be helpful for the prevention of PAD in diabetics even in populations traditionally accustomed to a Mediterranean dietary habit.


Integrated study of metal behavior in Mediterranean stream ecosystems: a case-study.
The objective of the present work was to assess the ecosystem status of Francolí river (Catalonia, Spain), a Mediterranean stream basin with contrasting human influences. An integrated approach was designed by combining physicochemical, biological and ecotoxicological analyses. The content of metals (As, Cd, Cr, Co, Cu, Hg, Ni, Pb, and Zn) was analyzed in samples of water, benthic sediments and aquatic macroinvertebrates. In addition, the potentially bioavailable fraction of metals in water and sediments was determined by using diffusive gradient in thin-films (DGTs) and sequential extraction of sediments (BCR), respectively. The biological quality was evaluated through aquatic macroinvertebrate communities, while the ecotoxicological status was assessed by Microtox(®) with Vibrio fischeri. Finally, an analysis of acid-volatile sulfide (AVS) and simultaneously extracted metals (SEM) was performed to evaluate the sediment toxicity associated to metal content. According to the results, DGTs and BCR are suitable methodologies to predict the potential bioavailable fraction of metals in freshwater systems. Moreover, ecotoxicity evaluation by means of V. fischeri, in combination with the chemical characterization and the biological quality assessment, should be complementarily used to get a better diagnose of freshwater systems.


The cytochrome c peroxidase and cytochrome c encounter complex: the other side of the story.
Formation of an encounter complex is important for efficient protein complex formation. The encounter state consists of an ensemble of orientations of two proteins in the complex. Experimental description of such ensembles inherently suffers from insufficient data availability. We have measured paramagnetic relaxation enhancements (PRE) on cytochrome c peroxidase (CcP) caused by its partner cytochrome c (Cc) carrying a spin label. The data complement earlier PRE data of spin labelled CcP, identifying several new interactions. This work demonstrates the need of obtaining as many independent data sets as possible to achieve the most accurate description of an encounter complex.


From inclusion to independence--training consumers to review research.
Health and medical research invariably impacts on the lives of everyday people. Organisations in the developed world are increasingly involving the public in health research projects, and research governance structures and processes. The form the involvement takes varies, as does the level of involvement, from individuals, to groups, to the wider community. Lay community members can be trained to independently review health and medical research, and wider societal involvement in funding decisions, can be effectively fostered. The theoretical foundation, design and development of a task based consumer-training program, including a number of enabling factors to support the success of such training are presented. This work is likely to be of value to those planning to train consumers in technical or complex areas.


Prevalence and Associated Risk Factors for Anemia in Pregnant Women in White Nile State, Sudan: A Cross-Sectional Study.
Anemia during pregnancy can lead to several adverse maternal and perinatal outcomes. Despite preventive measures, anemia during pregnancy remains a threatening health problem, especially in sub-Saharan African countries. We aimed to determine the prevalence of, and factors associated with, anemia among pregnant women at Rabak Maternity Hospital, Sudan. We conducted a cross-sectional study involving pregnant women who presented to Rabak Maternity Hospital from September to December 2021. Questionnaires were completed via face-to-face interviews to gather both obstetric and sociodemographic information (i.e., age, parity, history of miscarriage, education, level of antenatal care), and hemoglobin levels were estimated. A logistic regression analysis was performed. The median (interquartile range) of the age and parity of the 208 women enrolled in the study was 25 (21.0-30.0) years and 2 (1-4), respectively. Forty-five (21.6%) women did not use iron-folic acid during the index pregnancy. Eighty-eight (42.3%) women had anemia, and four (1.9%) had severe anemia. In the univariate analysis, age, parity, history of miscarriage, interpregnancy interval, education, and antenatal care level were shown not to be associated with anemia. A higher number of women with anemia did not use iron-folic acid during the index pregnancy than those without anemia (29/80 [33.0%] vs. 16/120 [13.3%], respectively, p = .001). Not taking iron-folic acid was found to be associated with anemia in the multivariate analysis (adjusted odds ratio = 3.19, 95% confidence interval = 1.60-6.63). Anemia was found to be a major health problem among the pregnant women in this study. There is no clear evidence across the women with anemia that their anemia stems from lack of using iron-folic acid (in fact, some women used iron-folic acid and they were anemic). There is a possibility that using iron-folic acid may prevent anemia in this part of Sudan.


Combined surgical strategy for management of unilateral exotropic Duane retraction syndrome associated with limitation of abduction.
To report the effect of asymmetrical bilateral lateral rectus recession combined with augmented partial vertical rectus transposition (VRT) in the management of exotropia, head turn, limited abduction, and anomalous vertical movements associated with unilateral exotropic Duane retraction syndrome (XT-DRS). The medical records of all patients with unilateral XT-DRS associated with limitation of abduction who underwent surgery during a 5-year period from 2013 to 2018 with at least 6 months' follow-up were reviewed retrospectively. Outcome measures were changes in head turn, primary position distance and near exodeviation, degree of limited abduction, and anomalous vertical movements on adduction. A total of 11 patients (6 males) were included. Mean patient age was 16.3 years (range, 6-29). Exodeviation at distance and near fixation were corrected by means of 26.4Δ and 24.8Δ, respectively. Head turn was improved by a mean of 17.3°. Limited abduction and anomalous vertical movements were corrected by means of 1.6 and 1.5 units, respectively. No patients developed symptomatic induced vertical deviation or anterior segment ischemia. In our study cohort, the combined strategy of asymmetrical bilateral lateral rectus recession with unilateral augmented partial VRT yielded satisfactory results in the management of unilateral XT-DRS associated with limited abduction with no recorded intra- or postoperative complications.


Unplanned hospitalizations in older patients with cancer: Occurrence and predictive factors.
This study aims to investigate the occurrence of unplanned hospitalizations in older patients with cancer and to determine predictive factors. A prospective Belgian multicentre (n = 22), observational cohort study was performed. Patients ≥70 years with a malignant tumor were included. Patients underwent G8 screening followed by geriatric assessment (GA) if abnormal at baseline and were followed for unplanned hospitalizations at approximately three months. Uni- and multivariable regression models were performed to determine predictive factors associated with unplanned hospitalizations in older patients with an abnormal G8. In total, 7763 patients were included in the current analysis of which 2409 (31%) patients with a normal G8 score and 5354 (69%) with an abnormal G8 score. Patients with an abnormal G8 were hospitalized more frequently than patients with a normal G8 (22.9% versus 12.4%; p < 0.0001). Reasons for unplanned hospitalizations were most frequently cancer related (25.7%) or cancer therapy related (28%). In multivariable analysis, predictive factors for unplanned hospitalizations in older patients with cancer and an abnormal G8 were female gender, absence of surgery, chemotherapy, ADL dependency, malnutrition and presence of comorbidities. Older patients with cancer and an abnormal G8 screening present a higher risk (23%) for unplanned hospitalizations. Predictive factors for these patients were identified and include not only patient and treatment related factors but also GA related factors.


Polycyclic aromatic hydrocarbons (PAHs) in meat, poultry, fish and related product samples of Iran: a risk assessment study.
Meat, poultry, and seafood such as fish are a valuable source of protein, vitamins and minerals. Considering their high consumption in the human diet, it is necessary to study pollutants (such as PAHs) in them. This present study has focused on the PAHs level and probabilistic risk of health in meat, poultry, fish and related product samples by MSPE-GC/MS technique (magnetic solid-phase extraction with gas chromatography-mass spectrometry). The maximum mean of 16 PAH was detected in smoked fish samples (222.7 ± 13.2 μg/kg) and the minimum mean of 16 PAH was detected in chicken (juje) kebab (112.9 ± 7.2 µg/kg μg/kg). The maximum mean of 4PAHs was detected in tuna fish (23.7 ± 2.4 µg/kg) and the minimum mean of 4PAHs was seen in grilled chicken and sausage samples (non-detected). Our results showed the 4PAHs and B[a]P were lower than the EU (European Union) standard levels (these standard levels were 30 and 5 μg/kg, respectively). Furthermore, the correlation among the type and concentrations of PAHs congeners was investigated through cluster analysis by heat map and principal component analysis. The 90th percentile ILCR (incremental lifetime cancer risk) of PAH compounds in fish, poultry, meat and related products samples was 3.39E-06, which was lower than the maximum acceptable level of risk (10-4). Finally, the highest ILCR was related to hamburger (4.45E-06). Therefore, there is no risk in consuming these foods in Iran, but it is necessary to monitor PAHs concentration in different types of foods.


Higher tax and less work: reverse "Keep up with the Joneses" and rising inequality.
To counteract excessive effort due to relative income comparison among identical agents, the literature suggests a tax response equal to the negative externality. Assuming a general income distribution, we show that an optimal tax must be higher under a general social welfare function, to not only reduce inefficiency but also inequality. We recommend a practical tax response to stronger comparison - to hold employment constant, which does not require unrealistic information including unobservable comparison. Surprisingly, the tax response will dominate the comparison effect and reduce labour supply or reverse "keeping up with the Joneses" on intensive margins, and also reverse the otherwise rising inequality. The online version contains supplementary material available at 10.1007/s00712-023-00821-2.


Utility of coagulation analyses to assess thromboprophylaxis with dalteparin in intensive care unit patients.
The aim of this study was to evaluate the utility of coagulation analyses to assess thromboprophylaxis with dalteparin in intensive care unit (ICU) patients. Prospective observational study of ICU patients receiving dalteparin prophylaxis at Oslo University Hospital in Norway. Trough and peak antithrombin, protein C, anti-factor Xa activity (aFXa), d-dimer, thromboelastography, calibrated automated thrombogram and microparticles were analysed. Levels were compared in patients with and without venous thromboembolism (VTE), major bleeding, acute kidney injury (AKI) with use of renal replacement therapy (RRT) and variable dalteparin dose. Among 50 included patients (76% male, mean age 62 years) five (10%) developed VTE and eight (16%) major bleeding. Median through aFXa level was 0.03 (0.02-0.05) IU/mL, and 48 (96%) of patients were within and two (4%) above target range. Peak aFXa level was 0.21 (0.13-0.29) IU/mL, the number of patients below, within and above prophylactic range were 21 (42%), 25 (50%) and four (8%). Peak aFXa levels were similar in patients with and without VTE (0.18 vs 0.21 IU/L, P = .72), major bleeding (0.22 vs 0.21 IU/mL, P = .38) and AKI with RRT (0.18 vs 0.24, P = .13), but lower in patients receiving dalteparin 5000 IU od compared to 7500 IU od (0.19 vs 0.30 IU/mL, P < .01). Intensive care unit patients receiving dalteparin prophylaxis had half of patients within prophylactic peak aFXa target range. Peak aFXa levels was affected by administered dalteparin dose, but not presence of VTE, major bleeding or AKI with RRT.


[Mycobacterium bovis in wildlife of the dairy regions of Santa Fe (Argentina)].
Control eradication campaigns of bovine tuberculosis based on the «test and slaughter» approach were successful in many countries and regions; however, in some areas the infection persists and one of the main reasons is Mycobacterium bovis infection in wild life species. Argentina has applied the same approach since 1999, achieving progress in dairy cattle herds. Nonetheless, the wildlife role has never been investigated. The objective of this study was to determine if wildlife from the Santa Fe dairy area is infected with M. bovis. Wildlife species having a positive tuberculin skin test were captured in five dairy farms. Ninety five wildlife mammals were captured; M. bovis was recovered from 7 possums (Didelphys albiventris), from one fox (Lycolapex gimnocercus) and from one rat (Rattus norvegicus). None of the animals exhibited macroscopic lesions. The most frequently isolated M. bovis spoligotypes were types 34 (4 isolates) and 12 (3 isolates). Spoligotype 34 is the most frequently isolated type in Argentine cattle. The role of D. albiventris as spillover host of M. bovis is discussed in this study.


Impact of Saccharomyces cerevisiae and Metschnikowia fructicola autochthonous mixed starter on Aglianico wine volatile compounds.
Non-Saccharomyces yeasts are metabolically active during grape must fermentations and can contribute with enzymes and metabolites to enhance the complexity and to define the final wine aroma. Nowadays, the use of non-Saccharomyces yeasts in combination with Saccharomyces cerevisiae is a state-of-the art strategy to improve wine composition and/or wine sensory properties. The present paper deals with the new yeast strains of Metschnikowia fructicola and S. cerevisiae, that were selected as representatives of the yeast microbiota isolated from grapes and grape juice of Aglianico cultivar. S. cerevisiae was utilized both as single strain starter and in combination with M. fructicola in experimental fermentations of Aglianico must. The dynamic of yeast populations was evaluated during the fermentation process analyzing the wine volatile compounds profile. The volatile compounds were identified by SPME-GC/MS. The results, showed that the multiple indigenous yeast starter was able to modulate the volatile compounds profiles and improve the aromatic complexity of wine, with a higher content of esters and terpenes.


Efficacy of neuroendoscopic surgery versus craniotomy for supratentorial hypertensive intracerebral hemorrhage: A meta-analysis of randomized controlled trials.
Hypertensive cerebral hemorrhage (HCH) is a potentially life-threatening neurological condition with an extremely high morbidity and mortality. In recent years, neuroendoscopy has been used to treat intracerebral hemorrhage (ICH). However, the choice of neuroendoscopic surgery versus craniotomy for patients with intracerebral hemorrhages is controversial. We conducted this meta-analysis to assess the efficacy of neuroendoscopic surgery compared with craniotomy in patients with supratentorial hypertensive ICH. A systematic electronic search was conducted of online electronic databases: PubMed, Embase, and the Cochrane Library updated on December 2017. The meta-analysis only included randomized controlled studies. Three randomized controlled trials met our inclusion criteria. The pooled analysis of death showed that neuroendoscopic surgery decreased the rate of death when compared with craniotomy (RR = 0.58, 95% CI 0.26-1.29; p = .18). The pooled result of complications indicated that neuroendoscopic surgery has a tendency toward lower complications (RR = 0.37, 95% CI 0.28-0.49; p < .001). Our results suggested that neuroendoscopic surgery has lower complications, but no superior advantages in morbidity rates. Since the advantage of neuroendoscopic surgery has been performed in some area, the continuation of multi-center comparative investigation with craniotomy may be necessary. Moreover, some efforts need to be taken in selecting appropriate patients with different treatments.


Correction: The Use of Person-Centered Language in Medical Research Journals Focusing on Psoriasis: Cross-sectional Analysis.
[This corrects the article DOI: 10.2196/28415.].


Protective effect of 6-O-methyl-scutellarein on repeated cerebral ischemia/reperfusion in rats.
Scutellarin (1) possesses protective effects against neuronal injury, while 6-O-methyl-scutellarein (3), as the main metabolite of scutellarin in vivo, has not been reported about its protective effects previously. The present study mainly investigated whether the neural injury caused by ischemia/reperfusion would be influenced by different doses of 6-O-methyl-scutellarein (3). The results of behavioral, neurological, and histological examinations indicated that 6-O-methyl-scutellarein (3) could improve neuronal injury, and exhibit significant difference among the various doses. More importantly, 6-O-methyl-scutellarein (3) had better protective effects than scutellarin in rat cerebral ischemia.


Familial Os Odontoideum.
To add to the confusion in the debate on pathogenesis of os-odontoideum, an additional report of its occurrence in two members of the same family is reported. This is a report of a rare coincidence wherein both father (51 years old) and daughter (25 years old) were diagnosed to have os odontoideum and presented with crippling neurologic deficits. Following atlantoaxial fixation, both recovered in their symptoms. Investigations revealed no genetic abnormality. Literature on the subject is briefly reviewed.


Plasma Parathyroid Hormone Is Independently Related to Nocturnal Blood Pressure in Hypertensive Patients: The Styrian Hypertension Study.
High parathyroid hormone (PTH) has been linked with high blood pressure (BP), but the relationship with 24-hour ambulatory blood pressure monitoring is largely unknown. The authors therefore analyzed cross-sectional data of 292 hypertensive patients participating in the Styrian Hypertension Study (mean age, 61±11 years; 53% women). Median plasma PTH (interquartile range) determined after an overnight fast was 49 pg/mL (39-61), mean daytime BP was 131/80±12/9 mm Hg, and mean nocturnal BP was 115/67±14/9 mm Hg. In multivariate regression analyses adjusted for BP and PTH-modifying parameters, PTH was significantly related to nocturnal systolic and diastolic BP (adjusted β-coefficient 0.140 [P=.03] and 0.175 [P<.01], respectively). PTH was not correlated with daytime BP readings. These data suggest a direct interrelationship between PTH and nocturnal BP regulation. Whether lowering high PTH concentrations reduces the burden of high nocturnal BP remains to be shown in future studies.


Synthesis, Insecticidal Activities, and Structure-Activity Relationship of Phenylpyrazole Derivatives Containing a Fluoro-Substituted Benzene Moiety.
Fluorinated organic compounds represent a growing and important family of commercial chemicals. Introduction of fluorine into active ingredients has become an effective way to develop modern crop protection products. Given the particular properties of fluorine and high efficiency and selectivity of diamide insecticides, we designed and synthesized 27 anthranilic diamides analogues containing fluoro-sustituted phenylpyrazole. A preliminary bioassay indicated that most target compounds exhibited good biological activity against Mythimna separata and Plutella xylostella. Compound IIIf containing a 2,4,6-trifluoro-substituted benzene ring showed 43% insecticidal activity against M. separata at 0.1 mg L-1, while the control chlorantraniliprole was 36%. The activity of IIIe against P. xylostella at 10-5 mg L-1 was 94%, compared with that of the control being 70%. Thus, introduction of fluorine into diamide insecticides was useful for increasing activity. Insect electrophysiology studies showed that the calcium concentration in the nerve cells of third M. separata larvae was elevated by IIIf, which further confirmed that ryanodine receptor (RyR) was its potential target.


Visual diagnosis: Enucleation status post gunshot wound to the head: A visual diagnosis/case report.
We present the case of a patient who attempted to commit suicide via a gunshot to the head. However, instead of ending his life, he destroyed both of his eyes. Computed tomography scans are shown.


Structure, molecular evolution, and hydrolytic specificities of largemouth bass pepsins.
The nucleotide sequences of largemouth bass pepsinogens (PG1, 2 and 3) were determined after molecular cloning of the respective cDNAs. Encoded PG1, 2 and 3 were classified as fish pepsinogens A1, A2 and C, respectively. Molecular evolutionary analyses show that vertebrate pepsinogens are classified into seven monophyletic groups, i.e. pepsinogens A, F, Y (prochymosins), C, B, and fish pepsinogens A and C. Regarding the primary structures, extensive deletion was obvious in S'1 loop residues in fish pepsin A as well as tetrapod pepsin Y. This deletion resulted in a decrease in hydrophobic residues in the S'1 site. Hydrolytic specificities of bass pepsins A1 and A2 were investigated with a pepsin substrate and its variants. Bass pepsins preferred both hydrophobic/aromatic residues and charged residues at the P'1 sites of substrates, showing the dual character of S'1 sites. Thermodynamic analyses of bass pepsin A2 showed that its activation Gibbs energy change (∆G(‡)) was lower than that of porcine pepsin A. Several sites of bass pepsin A2 moiety were found to be under positive selection, and most of them are located on the surface of the molecule, where they are involved in conformational flexibility. The broad S'1 specificity and flexible structure of bass pepsin A2 are thought to cause its high proteolytic activity.


Potential role of cysteine and methionine in the protection against hormonal imbalance and mutagenicity induced by furazolidone in female rats.
The use of nitrofurans as veterinary drugs has been banned in the EU since 1993 due to doubts on the safety of the protein-bound residues of these drugs in edible products. Furazolidone (FUZ) is a nitrofuran drug, which has been used for many years as an antibacterial drug in veterinary practice. The aim of the current study is to investigate the role of L-cysteine and L-methionine in the protection against hormonal imbalance and the genotoxicity induced by FUZ using the micronucleus (MN) assay and random amplified polymorphism DNA (RAPD-PCR) analysis in female rats. Forty female Sprague-Dawley rats were divided into four groups included the untreated control group; a group treated with FUZ (300 mg/kg b.w.); a group treated with a mixture of L-cysteine (300 mg/kg b.w.) and L-methionine (42.8 mg/kg b.w.) and a group treated with FUZ plus the mixture of L-cysteine and L-methionine for 10 days. The results indicated that FUZ induced hormonal disturbances involving thyroid, ovarian and adrenal hormones. Moreover, FUZ increased the micronucleus formation and induced changes in polymorphic band patterns. The combined treatment with FUZ and the mixture of L-cysteine and L-methionine succeeded to prevent or diminish the endocrine disturbance and the clastogenic effects of FUZ. The current study is casting new light on the complex mechanisms underlying the ameliorating action of dietary L-cysteine and L-methionine against FUZ toxicity in experimental animals.


Preventing neonatal hepatitis B infection during the perinatal period.
In the United States, hepatitis B virus (HBV) infection is a growing problem with serious long-term consequences. Because previous vaccination programs have been ineffective in lowering the incidence of HBV, the U.S. Centers for Disease Control now recommend a comprehensive plan to reduce transmission of the virus. This article explores the epidemiology of HBV infection, the use of hepatitis B immune globulin and hepatitis B vaccines, and current recommendations for eliminating transmission of HBV during the perinatal period.


Phantom evaluation of a navigation system for out-of-plane CT-guided puncture.
The purpose of this phantom study was to assess a new real time electromagnetically-guided navigation system and compare it to standard computed tomography (CT) guidance. A prospective, randomized, comparative study was carried out over a two-day period. Operators without prior experience on the new navigation system sequentially attempted to puncture two 6 mm-diameter targets (one attempt for each target) with out-of-plane trajectories using both the standard CT-guided method and the new navigation station (NAV method). Intention-to-treat analysis was performed for 54 operators. Twenty-two operators out of 54 (40.7%) reached the target on first attempt with the NAV method versus none (0%) using CT-guidance (P<0.001). The median distance of the puncture from the center of the target was 3.7mm [Q1-Q3=2-6.7] using NAV versus 15 mm [10-20] using CT-guidance (P<0.001). Overall planning and puncture time were shorter using NAV: 76s [50-118] versus 214s [181-264] using CT-guidance (P<0.001). Novice operators consistently performed faster and more accurate phantom punctures with out-of-plane trajectories using the electromagnetically-guided navigation system than with the standard CT-guided method.


[Effects of bacteria-feeding nematode at its different density on bacterial number, bacterial activity and soil nitrogen mineralization].
A gnotobiotic microcosm experiment was conducted to study the interactions between bacteria-feeding nematode Caenorhabditis elegans and bacterium Bacillus subtilis, and their effects on soil nitrogen mineralization at different Caenorhabditis elegans density. The results showed that the inoculation of the nematode stimulated the growth of the bacterium, and the increment was in order of 20>10>40 nematodes x g(-1) dried soil. The interaction between Caenorhabditis elegans and Bacillus subtilis significantly enhanced soil respiration rate and soil invertase, urease and phosphatase activities, with no significant differences among three test nematode densities. The inoculation of bacterial-feeding nematode markedly increased soil NH4+ -N and mineral N, suggesting that soil N mineralization was enhanced under the effect of the nematode. The increment of soil nitrogen mineralization at different nematode density was also in the same order mentioned above.


Ambient particulate matter (PM2.5) exposure contributes to neurodegeneration through the microbiome-gut-brain axis: Therapeutic role of melatonin.
Exposure to ambient particulate matter (PM2.5) has been shown to disturb the gut microbiome homeostasis and cause initiation of neuroinflammation and neurodegeneration via gut-brain bi-directional axis. Polyaromatic hydrocarbons (PAHs), which are carcinogenic and mutagenic, are important organic constituents of PM2.5 that could be involved in the microbiome-gut-brain axis-mediated neurodegeneration. Melatonin (ML) has been shown to modulate the microbiome and curb inflammation in the gut and brain. However, no studies have been reported for its effect on PM2.5-induced neuroinflammation. In the current study, it was observed that treatment with ML at 100 µM significantly inhibits microglial activation (HMC-3 cells) and colonic inflammation (CCD-841 cells) by the conditioned media from PM2.5 exposed BEAS2B cells. Further, melatonin treatment at a dose of 50 mg/kg to C57BL/6 mice exposed to PM2.5 (at a dose of 60 µg/animal) for 90 days significantly alleviated the neuroinflammation and neurodegeneration caused by PAHs in PM2.5 by modulating olfactory-brain and microbiome-gut-brain axis.


[Relationship between left ventricle dysfunction and the development of neuropathy in patients with type 2 diabetes mellitus].
The prevalence of left ventricular diastolic dysfunction was evaluated in 127 patients aged 22-66 yr with type 2 diabetes mellitus (DM2) without CHD. 69 (54.3%) of them presented with arterial hypertension that increased severity of diastolic dysfunction and the frequency of left ventricular concentric hypertrophy. Diastolic dysfunction in the absence of arterial hypertension was related to poor compensation of DM2 (HbA1c 7.5%) associated with the risk of microangiopathy and demyelinating neuropathy.


Optical screening of diabetes mellitus using non-invasive Fourier-transform infrared spectroscopy technique for human lip.
The Fourier-transform mid-infrared spectroscopy (FTIR) technique has not been used for diabetes diagnosis so far in clinical practice. We attempted to predict non-invasively blood hemoglobin A1c (HbA1c) levels by FTIR to enable evaluation and screening for diabetes. Twenty eight patients from age 20s to 80s, 14 males and 14 females, with and without diabetes, were examined in hospital as a pilot study, and their biochemical data were analyzed with infrared (IR) spectral data of the lip surface by FTIR spectroscopy. Some IR peaks of lip surface had significant correlations with blood glucose and HbA1c levels. Among several peaks in the spectra of lip, peaks at around 1300-1400cm(-1) discriminated groups with higher or lower HbA1c levels, suggesting the observation of lip surface advanced glycation end-products with carboxymethyl group. The application of partial least squares (PLS) regression analysis to the correlation between HbA1c levels and lip FTIR spectra resulted in highly significant prediction of HbA1c values for the subjects. Comparison of some IR peaks with predicted HbA1c values served to remove false-negative data effectively. This study with FTIR technique proposed here was effective for screening of diabetes patients with higher HbA1c levels.


Shutdown of multidrug transporter bmrCD mRNA expression mediated by the ribosome-associated endoribonuclease (Rae1) cleavage in a new cryptic ORF.
Rae1 is a well-conserved endoribonuclease among Gram-positive bacteria, cyanobacteria, and the chloroplasts of higher plants. We have previously shown that Rae1 cleaves the Bacillus subtilis yrzI operon mRNA in a translation-dependent manner within a short open reading frame (ORF) called S1025, encoding a 17-amino acid (aa) peptide of unknown function. Here, we map a new Rae1 cleavage site in the bmrBCD operon mRNA encoding a multidrug transporter, within an unannotated 26-aa cryptic ORF that we have named bmrX Expression of the bmrCD portion of the mRNA is ensured by an antibiotic-dependent ribosome attenuation mechanism within the upstream ORF bmrB Cleavage by Rae1 within bmrX suppresses bmrCD expression that escapes attenuation control in the absence of antibiotics. Similar to S1025, Rae1 cleavage within bmrX is both translation- and reading frame-dependent. Consistent with this, we show that translation-dependent cleavage by Rae1 promotes ribosome rescue by the tmRNA.


The host range and selectivity of a parasitic plant: Rhinanthus minor L.
Rhinanthus minor (Yellow-rattle) is a widespread hemiparasitic plant of grassland habitats throughout Britain. Association analysis of the dune vegetation at Holme-next-the-Sea in eastern England revealed only two potential host plants through positive association. In contrast direct examination of the root systems revealed haustorial connections with 20 host species. The number of species parasitized by one plant ranged from one to seven. Data from another four sites in Britain and one in central Europe indicate that the natural host range of R. minor encompasses at least 50 species from 18 families with 22% in the Leguminosae and 30% in the Gramineae. Comparison of the number of haustorial connections made to each species with the abundance of roots in the soil shows that R. minor is a highly selective parasite, but that the selectivity is not consistent between populations or between plants from different parts of the same population. The reasons for host selectivity are discussed.


Human Papillomavirus Prevalence and Integration Status in Tissue Samples of Bladder Cancer in the Chinese Population.
Human papillomavirus (HPV) infection is associated with multiple types of cancer, but the evidence has not yet been fully elucidated in bladder cancer. Frozen tissue samples collected from 146 patients aged 32 to 89 years with bladder cancer pathological diagnosis between 2015 and 2019 were analyzed. HPV genotyping and integration status determination were performed by capture-based next generation sequencing. Statistical analysis of HPV type distributions was performed according to stage, grade, sex, and age group of patients. Mean (SD) age of the 146 patients was 66.64 ± 10.06 years and 83.56% were men. Overall HPV infection rate was 28.77% (37.50% in women and 27.05% in men), with 11.90% HPV integration events. Among them, 17.12% single and 11.65% coinfections were observed. HPV18 (24.66%) was the most prevalent genotype, followed by HPV33, 16, and 39. All HPV were European lineage (A). HPV16 was more prevalent in women (P = .04). HPV infection may contribute to the etiology both in men and women with bladder cancer. HPV18, followed by HPV33, 16, and 39 genotypes, potentially represent the predominant oncogenic risk types for bladder carcinogenesis.


Relationship between self-care behaviors and quality of life in patients with heart failure.
It has been generally agreed that cardiac failure is one of the common and devastating diseases due to its morbidity, mortality and rates of disability. Moreover, it has negative impacts on quality of life among sufferers. Meanwhile, improving quality of life among heart failure patients is essential. It can be suggested that people with self-care ability have a better quality of life. However, this issue may be affected by some cultural issues. Regarding a paucity of information on this aspect in Iran, this study aims to explore the relationship between self-care behaviors and quality of life in patients with heart failure. This study is carried out using a descriptive - analytical method. The sample size consists of 77 patients who consented to participate in the study and had ejection fraction <40%. The tools were demographic checklist, European heart failure self-care behavior scale, and SF-36 quality of life questionnaire. Data was gathered from the heart center of Imam Ali in Kermanshah-Iran. Data analysis was done using independent t-test, Mann Whitney, ANOVA, and Kruskal-Wallis tests by SPSS-24 software. The study sample was 77 participants, of which 45 were female and 51 lived in an urban area. The mean of self-care score was 39.42 ± 7.04, and most of the patients (67.5%) were in moderate level. The mean and SD of quality of life was estimated as 38.45 ± 17.28. The spearman correlation test showed no correlation between self-care and quality of life. However there was a correlation between marital status and self-care ability, in which it shows the higher scores in unmarried people (K2 = 7.75, P = 0.021), and the results indicated better quality of life in male (t = 2.68, P = 0.009), educated patients at the level of university (F = 7.60, P < 0.001), free job (F = 6.21, P < 0.001) and lived in the urban area (Z = 2.05, P = 0.04). In this study, there is no correlation between self-care behaviors and quality of life in which, this may be attributed to Iranian cultures and perspectives such as valuing live with the children and importance of their attention to elderly patients, which demanded more studies.


Race, Ethnicity, and 60-Day Outcomes After Hospitalization With COVID-19.
To examine racial and ethnic disparities in clinical, financial, and mental health outcomes within a diverse sample of hospitalized COVID-19-positive patients in the 60 days postdischarge. A cross-sectional study. A total of 2217 adult patients who were hospitalized with a COVID-19-positive diagnosis as evidenced by test (reverse-transcriptase polymerase chain reaction), a discharge diagnosis of COVID-19 (ICD-10 code U07.1), or strong documented clinical suspicion of COVID-19 but no testing completed or recorded owing to logistical constraints (n=24). Patient records were abstracted for the Mi-COVID19 data registry, including the hospital and insurer data of patients discharged from one of 38 participating hospitals in Michigan between March 16, 2020, and July 1, 2020. Registry data also included patient responses to a brief telephone survey on postdischarge employment, mental and emotional health, persistence of COVID-19-related symptoms, and medical follow-up. Descriptive statistics were used to summarize data; analysis of variance and Pearson chi-squared test were used to evaluate racial and ethnic variances among patient outcomes and survey responses. Black patients experienced the lowest physician follow-up postdischarge (n = 65, 60.2%) and the longest delays in returning to work (average 35.5 days). More than half of hospital readmissions within the 60 days following discharge were among nonwhite patients (n = 144, 55%). The majority of postdischarge deaths were among white patients (n = 153, 21.5%), most of whom were discharged on palliative care (n = 103). Less than a quarter of patients discharged back to assisted living, skilled nursing facilities, or subacute rehabilitation facilities remained at those locations in the 60 days following discharge (n = 48). Increased attention to postdischarge care coordination is critical to reducing negative health outcomes following a COVID-19-related hospitalization.


Two novel mutations found in a patient with 17alpha-hydroxylase enzyme deficiency.
Congenital adrenal hyperplasia resulting from 17alpha-hydroxylase deficiency (17OHD) is a rare disorder associated with hypertension. We describe a phenotypically and hormonally affected female patient with 17OHD. DNA sequencing of her CYP17 gene revealed a maternal heterozygous mutation in exon 2 (R125Q) and a paternal heterozygous mutation in exon 8 (R416H). These are novel mutations in the CYP17 gene that completely eliminate enzyme activity. Identification of novel mutations in the CYP17 gene is vital in understanding the molecular mechanisms of its deficiency and in providing additional information about the structure and enzymatic functions of P450c17.


Nodular cystic fat necrosis in a patient with erythema nodosum.
Nodular cystic fat necrosis shows a distinctive spectrum of clinical and histological features. Most of the lesions are mobile subcutaneous nodules in regions vulnerable to trauma, such as the elbows, knees, and shins. There have been no reports of an association with other conditions. The histology is characterized by encapsulated fat necrosis in which multiple, non-viable adipocytes are surrounded by condensed fibrous tissue. We report a case of early stage nodular cystic fat necrosis associated with erythema nodosum.


Regional differences in postischemic recovery in the stunned canine myocardium.
To determine if differences exist in the degree of ischemic damage and in postischemic recovery when different coronary arteries are occluded and reperfused, 40 barbital-anesthetized dogs were subjected to brief 15-minute periods of coronary artery occlusion followed by 3 hours of reperfusion ("stunned" myocardium) of the left anterior descending (LAD) or the left circumflex (LCX) coronary arteries. Myocardial segment shortening (%SS) in the subendocardium of nonischemic and ischemic reperfused areas was measured by sonomicrometry, and regional myocardial blood flow was measured by radioactive microspheres. Transmural tissue biopsies were taken at the end of reperfusion for the measurement of adenine nucleotides and total tissue water content. Arterial and local coronary venous blood samples were collected during preocclusion, during occlusion, and at 30 and 180 minutes of reperfusion for determination of blood oxygen content and oxygen consumption in the ischemic area. During occlusion, subendocardial blood flow (LAD flow = 0.11 +/- 0.02; LCX flow = 0.15 +/- 0.04 ml/min/gm), myocardial oxygen consumption (LAD = 2.4 +/- 0.7; LCX = 2.7 +/- 0.7 ml/min/100 gm), and areas of the left ventricle at risk (LAD = 27.4 +/- 2.3%; LCX = 32.4 +/- 2.4) were similar in both groups, thus indicating equivalent degrees of ischemia. There were no differences between groups in hemodynamics throughout the experiment or in the loss of myocardial high-energy phosphates or increase in total tissue water in the ischemic reperfused area at 3 hours of reperfusion. There was a significantly greater loss (p less than 0.05) of systolic wall function during LAD versus LCX occlusion and a greater recovery of segment function from 5 minutes throughout 1 hour of reperfusion after LCX occlusion (p less than 0.05), with no difference in %SS at 2 and 3 hours following reperfusion. Thus, although similar changes occurred in blood flow, metabolite parameters, tissue edema, wall function, and overall hemodynamics when either the LAD or LCX perfusion territories were occluded and reperfused, the loss of systolic wall function and recovery of segment shortening were more variable after regional stunning of the LCX perfusion bed. These data suggest that evaluation of pharmacologic or surgical interventions to improve postischemic functional recovery may be more reliably performed when the LAD coronary artery is the vessel occluded.


Mechanical tricuspid valve replacement is not superior in patients younger than 65 years who need long-term anticoagulation.
We evaluated long-term results of tricuspid valve replacement (TVR) with mechanical valves and bioprostheses in patients less than 65 years old who needed anticoagulation therapy irrespective of TVR. Among 156 patients who underwent TVR from January 1996 to April 2010, 119 patients younger than 65 years who needed anticoagulation therapy independent of the TVR were studied. Anticoagulation therapy was needed owing to left-sided mechanical valves (n = 11), atrial fibrillation (n = 13), or both (n = 95). Seventy patients underwent mechanical TVR, and 49 underwent bioprosthetic TVR. The follow-up duration was 68 ± 38 months. Propensity score-adjusted analyses were performed. Early postoperative outcomes were similar between groups, with an operative morality rate of 6.7% (8 of 119). Overall survival rates at 5 and 10 years were 86.4% and 80.3%, respectively. There were no differences in propensity score-adjusted overall survival rates between the two groups (p = 0.291). Freedom from the composite endpoint of thrombosis, embolism, and bleeding was lower in the mechanical TVR group than in the bioprosthetic TVR group (76.3% and 70.0% at 5 and 10 years, respectively, versus 97.6% and 97.6%, p = 0.020). Five- and 10-year valve-related event-free survivals were also lower in the mechanical TVR group than in the bioprosthetic TVR group, although not statistically significant (75.0% and 61.7% versus 89.2% and 80.3%, p = 0.129). Even in younger patients who need anticoagulation therapy irrespective of TVR, mechanical TVR is not superior because of increased occurrence of valve-related events, especially the composite of thrombosis, embolism, and bleeding.


Effects of empowerment education on patients after percutaneous coronary intervention: A meta-analysis and systematic review.
Empowerment education is a new nursing education model with great significance in the process of chronic disease rehabilitation, and a number of studies have found that it has good benefits for patients after percutaneous coronary intervention (PCI). But there is no meta-analysis on how empowerment education influence the life of patients after PCI. Our study intends to evaluate the impact of empowerment education on the quality of life, cognitive level, anxiety and depression level of patients after PCI. Systematic review and meta-analysis, following PRISMA guidelines. RevMan5.4 software and R software were used for statistical analysis. Mean difference or standard mean difference was used as effect analysis statistic for continuous variables with 95% confidence intervals. Six studies met the inclusion criteria, including 641 patients. The Exercise of Self-Care Agency Scale score of the experimental group was higher than that of the control group, with statistically significant difference. Empowerment education could increase the knowledge of coronary heart disease in patients after PCI, but the difference was not statistically significant. Significant effects of empowerment have been found in improving patients' quality of life and self-care ability. Empowerment education could be a safe exercise option in PCI rehabilitation. However, the effect of empowerment on cognitive level for coronary heart disease and the depression needs to carry out more large-sample, multi-center clinical trials. A data-analysis researcher and 3 clinicians are responsible for the writing, and no patients participated in the writing of this paper.


Unscheduled DNA replication in G1 causes genome instability and damage signatures indicative of replication collisions.
DNA replicates once per cell cycle. Interfering with the regulation of DNA replication initiation generates genome instability through over-replication and has been linked to early stages of cancer development. Here, we engineer genetic systems in budding yeast to induce unscheduled replication in a G1-like cell cycle state. Unscheduled G1 replication initiates at canonical S-phase origins. We quantifiy the composition of replisomes in G1- and S-phase and identified firing factors, polymerase α, and histone supply as factors that limit replication outside S-phase. G1 replication per se does not trigger cellular checkpoints. Subsequent replication during S-phase, however, results in over-replication and leads to chromosome breaks and chromosome-wide, strand-biased occurrence of RPA-bound single-stranded DNA, indicating head-to-tail replication collisions as a key mechanism generating genome instability upon G1 replication. Low-level, sporadic induction of G1 replication induces an identical response, indicating findings from synthetic systems are applicable to naturally occurring scenarios of unscheduled replication initiation.


Right ventricular variants and pulmonary embolism-association or coincidence?
It has been stated that the interior of the right ventricle is as unique to each individual as one's fingerprint. This statement is backed by numerous publications which demonstrates considerable variation in the number, shape and configuration of papillary muscles inside the normal right ventricle.It has also been shown that these variants may be the cause of cardiac rhythm disorders.In this case report another potential complication of such right ventricular papillary muscle variants is proposed-these muscles may be the source of pulmonary emboli.The pathogenesis may be that of local stasis around these aberrant muscular structures and/or emboli may form inside the right ventricle as a result of cardiac rhythm disorders, induced by these muscles.It is proposed that in future the role of the right ventricle as the source of pulmonary emboli will become more apparent and an important part of the diagnostic work up in cases of idiopathic pulmonary embolism.


Synthetic analogues and biosynthetic intermediates of bleomycin. Metal-binding, dioxygen interaction, and implication for the role of functional groups in bleomycin action mechanism.
In order to clarify the role of bleomycin functional groups in action mechanism, the metal-binding, dioxygen activation, and DNA cleavage of several synthetic analogues and biosynthetic intermediates of bleomycin have been investigated. The present results support that 1) the beta-aminoalaninepyrimidine-beta-hydroxyhistidine portion of the bleomycin molecule substantially participates in the Fe(II) and dioxygen interactions, 2) the transposition of the pyrimidine (or pyridine) and imidazole groups in the Fe(II)-coordination is essential for the effective binding and activation of molecular oxygen by the bleomycin ligands, and 3) the gulose-mannose moiety plays an important role as an environmental factor for the efficient dioxygen reduction and DNA cleavage, although the sugar portion does not contribute significantly to the nucleotide specificity in the DNA strand scission. Certain oligopeptides are able to mimic the metal-binding and dioxygen activation by bleomycin, but not induce the effective DNA cleavage. Probably, the bithiazole DNA interaction site of bleomycin delivers the iron/dioxygen chemistry to particularly the DNA (formula, see text) nucleotide sequences.


Euodionosides A-G: megastigmane glucosides from leaves of Euodia meliaefolia.
From a 1-BuOH-soluble fraction of the MeOH extract of leaves of Euodia meliaefolia, collected in Okinawa, seven megastigmane glucosides, named euodionosides A-G, were isolated together with three known megastgmane glucosides, and two aliphatic and three phenolic compounds. Their structures were elucidated through a combination of spectroscopic analyses and application of the modified Mosher's method.


The Canadian experience with Durata and Riata ST Optim defibrillator leads: a report from the Canadian Heart Rhythm Society Device Committee.
The St. Jude Medical Riata family of implantable cardioverter-defibrillator (ICD) leads has demonstrated a high rate of externalized conductors and electrical failure. Given similar design elements of Durata to Riata, the purpose of this study was to assess the rates of failure of the Riata ST Optim and Durata lead families in Canada. All Canadian ICD-implanting centers were invited to submit follow-up information on all Optim-coated ICD leads implanted. Electrical failure was defined as a rapid change in impedance or pacing capture threshold leading to lead revision, or oversensing due to noise. Externalized conductors were defined as appearance of conductor wires outside the lead body. Systematic fluoroscopic screening for externalized conductors was not performed. As of December 1, 2012, 15 of 25 centers provided data on 3981 leads (44% of those sold in Canada during the same timeframe): 3477 Durata and 504 Riata ST Optim leads. The most common model numbers were 7122 (1516 leads [38%]), 7121 (707 leads [18%]), and 7120 (622 leads [16%]). Mean follow-up duration from implant to December 1, 2012, was 4.47 ± 0.48 years for Riata ST Optim leads and 2.00 ± 1.10 years for Durata leads. The annual rate of lead failure was 0.27% per year for Riata ST Optim leads and 0.24% per year for Durata leads. No instances of externalized conductors were identified in the failed leads. No deaths were attributed to lead failure; however, 2 patients experienced inappropriate shocks due to lead failure. The overall electrical failure rates of the Riata ST Optim and Durata leads appear to be low, and no instances of externalized conductors were observed.


Strategy for studying health effects of pesticides/fertilizer mixtures in groundwater.
This paper is a "historical account" of the entire process leading to the final implementation of a toxicology research program on the health-effect studies of pesticide and fertilizer contaminants in groundwater conducted at the National Institute of Environmental Health Sciences/National Toxicology Program (NIEHS/NTP). Starting with the perception of a potential problem area, the program evolved through several stages, including planning and information-gathering, deliberation on experimental designs, formulation of a draft protocol, peer-review and public comments on the protocol, finalization of the protocol, announcement of open bidding to the NTP master agreement laboratories (i.e., a group of laboratories that has been previously evaluated and approved to conduct NTP toxicology contract work), implementation of chemistry developmental work, selection of toxicology laboratories and awarding of contracts, final implementation of toxicology studies, and cultivation of special collaborative efforts among NIEHS in-house scientists as well as colleagues at the neighbouring laboratories in Research Triangle Park. To put things in perspective, the author's present approach, a coupling of physiologically based pharmacokinetics/pharmacodynamics and computer modeling with the toxicology of chemical mixtures at Colorado State University, is used to address the issues of toxicology and risk assessment of chemical mixtures with respect to rationale and reality.