A Japanese family with FEOM1-linked congenital fibrosis of the extraocular muscles type 1 associated with spinal canal stenosis and refinement of the FEOM1 critical region.
We identified a Japanese family with congenital fibrosis of the extraocular muscles, including 24 affected individuals through five generations. To determine their form of congenital fibrosis of the extraocular muscles, we performed clinical and linkage studies. DNA typing for linkage to the FEOM1 (12p11.2-q12) and FEOM3 (16qter) loci was performed on genomic DNA, using fluorescent microsatellite polymorphic markers. All affected individuals shared the common manifestations of congenital fibrosis of the extraocular muscles type 1 including congenital ptosis, infraducted globe position in primary gaze, and upward gaze palsy in both eyes. Unexpectedly, we found apparent spinal canal stenosis in the cervical spine in all affected family members who were examined. Genetic analysis revealed linkage to the FEOM1 locus with a maximum lod score of 4.42 at theta of zero. One affected family member harbored a recombination event between D12S345 and D12S1692, narrowing the FEOM1 locus from the published 3-cM region flanked by D12S1584 and D12S1668 to a 2.1-cM region flanked by D12S345 and D12S1668. Thus, we have established that this family segregates congenital fibrosis of the extraocular muscles type 1 as an autosomal dominant trait and that their disorder both maps to and refines the FEOM1 locus. This is the first clinical and genetic report of such a family in the Japanese population and the first report of spinal involvement in congenital fibrosis of the extraocular muscles.


Reciprocal hemizygosity analysis of mouse hepatic lipase reveals influence on obesity.
We previously demonstrated coincident quantitative trait loci (QTLs) for percentage body fat, plasma hepatic lipase (HL) activity, and plasma cholesterol on mouse chromosome 7. In the present study, we investigated whether hepatic lipase (Lipc) is an obesity gene, whether Lipc interacts with an unknown gene on chromosome 7, and how HL activity is linked to the chromosome 7 locus. BSB mice are a model of complex obesity due to interactions among genes from C57BL/6J and Mus spretus (SPRET) in (C57BL/6J x SPRET) x C57BL/6J backcross mice. Five crosses tested the impact on obesity of combinations of inactive (knockout) and wild-type Lipc alleles from C57BL/6J or SPRET in a reciprocal hemizygosity analysis. The combined data from this allelic series suggest that Lipc alleles, and not alleles from a gene linked to Lipc, influence obesity. No interaction between Lipc and chromosome 7 was demonstrated. We confirmed the chromosome 7 QTLs for obesity, HL activity, and cholesterol. Because obesity and HL activity are not consistently associated in the BSB model, linkage of HL activity to chromosome 7 is not secondary to obesity per se. We also report, for the first time to our knowledge, a QTL in mammals for food intake. This use of reciprocal hemizygosity analysis in mammals, which, to our knowledge, is the first reported, reveals its power to detect previously unknown effects of Lipc on obesity.


The Western Washington Myocardial Infarction Registry and Emergency Department Tissue Plasminogen Activator Treatment Trial.
This study comprised a registry and an emergency department treatment trial using recombinant tissue plasminogen activator. During 1 year, 1,028 patients with documented acute myocardial infarction (AMI) were evaluated for eligibility for thrombolytic therapy. Of these, 221 patients (22%) were eligible for thrombolytic therapy under currently accepted criteria, 175 (79%) of them were correctly identified by emergency department physicians for thrombolytic therapy, and 160 were enrolled in the trial. Only 3 patients (2%) enrolled by emergency department physicians did not subsequently evolve documented AMI. In all, 807 patients (78%) were ineligible for thrombolytic therapy: 335 (33%) because of greater than or equal to 1 contraindications, 364 (36%) because of nondiagnostic electrocardiograms on presentation, and 105 (10%) because of age greater than 75 years, or greater than 6 hours of chest pain at presentation, or both. Mortality in treated patients at 14 days was 5.6%, and survival at 1 year was 92%. The mean time from hospital arrival to thrombolytic treatment was 55 +/- 27 minutes. Initial management of AMI with recombinant tissue plasminogen activator in the emergency department provided rapid and safe treatment comparable to that reported in trials that started treatment in the coronary care unit. The proportions of eligible patients could be increased from 1 in 5 to 1 in 3, if patients currently excluded only because of age greater than 75 years or because of greater than 6 hours of chest pain were offered treatment.


Proline-dependent regulation of collagen metabolism.
This review is focused on recent data on the role of proline (Pro) in collagen biosynthesis and cellular metabolism. It seems obvious that one of the main substrates for collagen biosynthesis Pro is required to form collagen molecule. The question raised in this review is whether the Pro for collagen biosynthesis is synthesized "de novo", comes directly from degraded proteins or it is converted from other amino acids. Recent data provided evidence that extracellular Pro (added to culture medium) had significant, but relatively little impact on collagen biosynthesis in fibroblasts (the main collagen synthesized cells) cultured in the presence of glutamine (Gln). However, extracellular Pro drastically increased collagen biosynthesis in the cells cultured in Gln-free medium. It suggests that Pro availability determines the rate of collagen biosynthesis and demand for Pro in fibroblasts is predominantly met by conversion from Gln. The potential mechanism of this process as well as possible implication of this knowledge in pharmacotherapy of connective tissue diseases is discussed in this review.


[FGF23 tumor induced osteomalacia].
Tumor induced osteomalacia is a rare acquired disease. The cause is a mesenchymal tumor secreting fibroblast growth factor 23 (FGF23). An excessive amount of FGF 23 disrupts the metabolism of phosphorus and vitamin D, which leads to severe paraneoplastic syndrome, manifested in the form of multiple fractures, severe pain in the bones and generalized myopathy. With oncogenic osteomalacia, a complete cure is possible with radical resection of the tumor. Unfortunately, localization, small size of formations and rare frequency of occurrence lead to the fact that the disease remains unrecognized for a long time and leads to severe, disabling consequences. A step-by-step approach to diagnosis improves treatment outcomes. First, a thorough anamnesis is collected, then functional visualization is performed and the diagnosis is confirmed by anatomical visualization of the tumor. After that, the method of choice is a surgical treatment. If resection is not possible, then conservative therapy with active metabolites of vitamin D and phosphorus salts is indicated. New therapeutic approaches, such as the antibody to FGF23 or the pan-inhibitor of receptors to FGF, are actively developing. This article provides an overview of modern approaches to the diagnosis and treatment of this disease.


Repair of Quadriceps and Patellar Tendon Tears.
Tears of the quadriceps or patellar tendon usually occur after a sudden eabccentric contraction and are diagnosed by a palpable gap at the injury site combined with an inability to perform a straight leg raise. Bilateral knee radiographs may demonstrate patella alta with patellar tendon tears and patella baja with quadriceps tendon tears compared with the uninjured knee. Ultrasound and magnetic resonance imaging can be helpful when there is uncertainty in the diagnosis. Surgical treatment is indicated for complete tears and some high-grade, partial tears. Nonabsorbable high-strength sutures or suture tape are placed in running locking fashion along the injured tendon and secured to the patella with bone tunnels (i.e., transosseous) or suture anchors. The transosseous technique requires exposure of the length of the patella to drill 3 bone tunnels to shuttle the sutures and tie over either pole of the patella. The suture anchor technique allows for a smaller incision and less soft-tissue dissection and may use a knotted or knotless technique. Biomechanical testing with load to failure is not statistically different between the transosseous and anchor techniques, although anchors have been shown to have less gap formation at the repair site. Repair augmentation with a graft may be beneficial in mid-substance injuries, chronic tears, and in cases of compromised tissue quality. Rehabilitation usually can be initiated immediately with protected weight-bearing in an orthosis, safe-zone knee passive range of motion, and avoidance of active extension. After a period of 6 weeks, rehabilitation can progress with full range of motion and a concentric strengthening program.


Isolated thoracic and lumbar transverse process fractures: Do they need spine surgeon evaluation? a high volume level I trauma center experience with cost analysis.
Transverse process fractures (TPF) of the thoracic and lumbar spine have become increasingly identified due to CT imaging. Spine service consultation is common for further evaluation and management. There are several studies that demonstrate no difference in clinical outcome with or without spine service intervention. However, no study to our knowledge provides an additional cost analysis. We hypothesize that isolated thoracolumbar TPF are stable injuries. Furthermore, spine service consultation and evaluation results in increased health care costs. Patients were identified using trauma registry data at Saint Louis University (SLU) from January 2012 to August 2018. Chart and imaging review was performed to determine if additional spine fractures were identified by the spine team which were not included in the initial radiology report. TPF associated with other spinal injuries were defined as one or more thoracic and/or lumbar TPF in addition to any other acute fracture or dislocation in the cervical, thoracic, or lumbar spine. A separate cost analysis with institution-specific charges was also performed. Six hundred eighty-two patients with TPF from January 2012 to August 2018 were identified. Two hundred twenty-eight patients met the criteria to be included in this study. Additional spinal pathology that was not included in the initial radiology report was identified in 5 (2.19%) patients, none of which required surgical intervention. Cost analysis demonstrated additional costs associated with spine service intervention totaled $1,725,360.28. Average cost per patient in our cohort summed to $2,529.85. These data support that isolated TPF of the thoracic and lumbar spine are stable injuries that likely do not require spine service intervention and in fact may represent unnecessary financial burden. Foregoing unnecessary consultation can alleviate time constraints within spine service practices and reduce health care costs by eliminating costly extraneous interventions from the patient's care.


Tear Film, Lacrimal Drainage System, and Eyelid Findings in Subjects With Anophthalmic Socket Discharge.
To compare the results of tear film and lacrimal drainage system tests between anophthalmic socket and normal eye and assess discharge characteristics and frequency of prosthesis removal (questionnaire), eyelid function, and meibomian glad dysfunction (MGD). Prospective masked case control. Subjects (≥6 years and ≥6 months of wearing prosthesis) with unilateral acquired anophthalmic socket discharge were included. Excluded was ocular adnexal abnormality of any reason and incomplete tests. The subjective questionnaire was completed. Blinking rate, lagophthalmos, eyelid laxity, MGD, Schirmer test, tear meniscus height, and dye disappearance test were assessed by a masked examiner. Another masked examiner performed an irrigation test 1 week later and interpreted the scintigraphy images at the end of the study. Included were 50 subjects (mean age: 31.3 years, mean prosthesis wear: 96.1 months). Discharge was frequent or very frequent in 85%, mucoid or mucopurulent in 90%, and moderate to severe in 86% of the subjects. MGD in 58%, lagophthalmos in 80%, and eyelid laxity in 46% were observed. Anophthalmic socket sides showed a significantly lower tear production and higher tear drainage obstruction. Subjects with frequent prosthesis removal had a significantly (P = .02) greater lagophthalmos and blinking rate (P = .04). The blinking rate was also significantly greater in subjects with higher frequency of discharge (P = .04). Tear film impairment (aqueous and lipid) and lacrimal drainage obstruction should be considered in subjects with anophthalmic socket discharge. A significantly higher blinking rate and lagophthalmos were found in subjects with higher frequency of prosthesis removal.


Delay in the surgical treatment of bladder cancer and survival: systematic review of the literature.
Eighty per cent of the newly diagnosed invasive bladder tumours are invasive from the outset. Half of these patients already have occult distant metastases reflecting the rapid nature of progression. The aim of the current study was to review the literature to determine if delay in cystectomy leads to worse prognosis and to determine if a possible cutoff point for delay exists, after which a worse outcome would be expected. We performed a systematic review of publications indexed in Medline and other scientific databases by analyzing types and causes of delay in performing radical cystectomy. Information on the impact of such delays on tumour recurrence and survival was collected and summarized. Papers that described only delay without any outcome correlation were excluded from the study. A total of 13 papers published from 1965 to 2006 were included in this study. Three (23%) papers did not find any correlation between pretreatment delays and survival. Two (15%) papers reported a trend towards worse survival with delay. Eight (62%) papers documented significant association between delay and worse prognosis. Delay influenced survival as an independent variable in two (25%) of these eight papers. In the remaining six (75%) manuscripts, delay was significantly associated with a higher pathologic stage. Although studies on bladder cancer failed to show a linear relationship between delay and prognosis, the majority confirmed that delays are associated with worse outcome. Studies suggested a window of opportunity of less than 12 weeks from diagnosis of invasive disease to radical cystectomy.


[The effect of beta-adrenoblockaders on the elasticity of the vessels of the greater circulation].
Experiments in anesthesized cats have shown that the two non-selective beta-adrenergic blocking drugs anapriline (propranolol) and tobanum (cloranolol hydrochloride) enhance vasodilation caused by increasing the blood flow volumetric velocity through the vascular region. It is suggested that the cause of increased vascular bed distensibility induced by these compounds is their capacity to release endothelium-relaxing factor. The cardiac selective beta-adrenoblocker metoprolol tartate had no effects on the regulation of vascular tone.


HLA-DR4 influences glial activity in Alzheimer's disease hippocampus.
The importance of inflammatory/immune mechanisms in Alzheimer's disease is supported by evidence that the human leukocyte antigen (HLA)-DR genotype influences risk of the disease, with a protective effect associated with the HLA-DR4 allele. We investigated the influence of the HLA-DR4 allele on glial activity, assessed by quantification of glial fibrillary acidic protein (GFAP), in hippocampal tissue from subjects with Alzheimer's disease. The mean GFAP level was significantly higher in Alzheimer's disease hippocampal specimens lacking the HLA-DR4 allele compared to specimens with similar neuropathological findings that were HLA-DR4 positive. Apolipoprotein E genotype had no influence on GFAP levels. These results indicate that HLA-DR4 may exert a protective influence on Alzheimer's disease via modulation of glial activity.


Mindfulness Improves Otolaryngology Residents' Performance in a Simulated Bad-News Consultation: A Pilot Study.
Delivering bad news is a stressful moment for both patient and clinician. As poor bad-news consultation quality may lead to misunderstandings, lack of treatment adherence, acute or even post-traumatic stress in patients, training interventions to improve communication skills and stress-management are necessary. Mindfulness is a recognised stress-management strategy that has shown its efficacy in reducing stress in both health professionals and students. We then supposed that a short mindfulness meditation session performed just before a simulated breaking bad-news consultation to patients with laryngeal cancer may help ear, nose and throat (ENT) residents to master their stress and improve their management of this consultation. This study aims at showing how a short mindfulness meditation performed before a simulated bad-news consultation may improve performance in its realisation by ENT residents. We enrolled 53 ENT residents, randomised in 2 groups. The first group completed a 5-minute mindfulness session while the other group listened to a control track. Thereafter, every resident completed an 8-minute simulated bad-news consultation with a standardised patient. Two blinded expert assessors evaluated their performance on a 25-point grid (BNC-OSAS). Residents self-assessed their stress before and after the intervention and simulated patients rated their perception of physician's empathy. The performance was significantly better in the mindfulness group than in the control group (m = 19.8, sd = 3.2 and m = 17.4, sd = 3.7 respectively, F(1,45)=5.27, p = 0.026, d = 0.67), especially in the communication and knowledge subdomains. There was no significant difference in perceived stress between the 2 groups. Empathy perceived by simulated patients was positively correlated to residents' performance. A short mindfulness meditation is effective for improving ENT residents' performance in a simulated bad-news consultation. These results encourage further assessments of this method with objective measures of physiological stress. More research is required concerning the feasibility and efficacy of mindfulness before daily clinical activities such as stressing bad-news consultation.


Validation of a first-trimester screening model for pre-eclampsia in an unselected population.
To validate the performance of a previously constructed first-trimester predictive model for pre-eclampsia (PE) in routine care of an unselected population. A validation cohort of 4621 consecutive women attending their routine first-trimester ultrasound examination was used to test a prediction model for PE that had been developed previously in 5170 women. The prediction model included maternal factors, uterine artery Doppler, blood pressure and pregnancy-associated plasma protein-A. Model performance was evaluated using receiver-operating characteristics (ROC) curve analysis and ROC curves from both cohorts were compared unpaired. Among the 4203 women included in the final analysis, 169 (4.0%) developed PE, including 141 (3.4%) cases of late-onset PE and 28 (0.7%) cases of early-onset PE. For early-onset PE, the model showed an area under the ROC curve of 0.94 (95% CI, 0.88-0.99), which did not differ significantly (P = 0.37) from that obtained in the construction cohort (0.88 (95% CI, 0.78-0.99)). For late-onset PE, the final model showed an area under the ROC curve of 0.72 (95% CI, 0.66-0.77), which did not differ significantly (P = 0.49) from that obtained in the construction cohort (0.75 (95% CI, 0.67-0.82)). The prediction model for PE achieved a similar performance to that obtained in the construction cohort when tested on a subsequent cohort of women, confirming its validity as a predictive model for PE. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.


Cardiovascular risk among urban Aboriginal people.
To describe the results of a program for detecting high cardiovascular risk in an urban Aboriginal community. Cardiovascular risk assessment program conducted between January 1998 and October 1999. Participants completed a questionnaire and underwent a physical assessment and biochemical tests. 738 self-selected members of the Perth Aboriginal community (332 men, 406 women; age range, 18-79 years). The participants represented approximately a fifth of the Perth Aboriginal population aged 25-64 years (those aged 18-24 years comprised < 5% of Aboriginals aged 15-24 years in Perth). Eighty-four per cent fell within National Heart Foundation "high risk" or "highest risk" categories for cardiovascular disease; 15% of men and 6% of women had an absolute risk of a cardiovascular event of over 15% within 10 years. A high proportion of participants reported diabetes, hypertension, smoking, overweight and obesity. A fasting plasma glucose level indicative of diabetes or impaired fasting glucose was found in 8.6% (95% CI, 6.2%-11%) of people not previously known to have diabetes. Obesity and smoking were twice as prevalent in study participants as in the general population. Less than a third of subjects with hypertension and diabetes had attained recommended target levels for blood pressure reduction or glycaemic control, and only a third of those at high risk and one in six of those at highest risk had attained recommended lipid-level targets. A cardiovascular risk assessment program with strong community support in an urban Aboriginal population can identify a significant number of people with high cardiovascular risk who are candidates for intensive risk-factor reduction strategies.


Intracavitary irradiation of endometrial carcinoma stage I by a high dose-rate afterloading technique.
Intracavitary irradiation was administered to 366 patients with endometrial carcinoma stage I by a high dose-rate afterloading method using 60Co sources (bulb technique). In 275 cases hysterectomy and bilateral salpingo-oophorectomy were performed 6 weeks later and in 91 cases dilation and curettage was used to verify tumor eradication. In 58% of the hysterectomy specimens no residual carcinoma was detected at the histopathologic evaluation. In the group treated with radiotherapy alone 74% showed no carcinoma remnants in the curettings 3 months after therapy. The effect of the fractionation dose was evaluated in relation to the outcome of the histopathologic examination. The proportion of specimens with no residual carcinoma increased from 27% for the 5 Gy per fraction group to 78% for the 10 Gy per fraction group. Recurrences were recorded in 13% in the hysterectomy group and in 29% in the group treated with radiotherapy alone. The 5-year corrected survival rate for the combination-treated group was 88% and for the group treated with radiotherapy alone 72%. If the dose per fraction is specified in the range of 5 to 8 Gy the high dose-rate afterloading technique seems safe with a tumor control rate and a frequency of radiation reactions comparable to the manual radium method.


Evaluation of oxindole derivatives as a potential anticancer agent against breast carcinoma cells: In vitro, in silico, and molecular docking study.
In this study we have performed the in vitro anticancer activity of spiro oxindole derivatives against MCF-7 (human Adreno carcinoma) and MDA-MB-231 (triple negative breast cancer) cell lines to propose a possible role of these derivatives in the treatment of cancer. Compound 6, which has an N-benzyl substitution with a chloro group on the indolin-2-one scaffold, had the most potent activity against MCF-7 (3.55 ± 0.49 μM) and MDA-MB-231 (4.40 ± 0.468 μM) of all the synthesized molecules. A normal mouse embryonic fibroblast (NIH/3 T3) cell line was used to test the cellular toxicity of these derivatives. The results showed that none of the compounds were cytotoxic to normal cells. In addition, pharmacokinetic (ADME) and toxicity study profiles were predicted in silico. All the synthesized derivatives (1 to 7) demonstrated the necessary physicochemical properties for bioavailability. Finally, in vitro results of promising compound 6 were validated using molecular docking and dynamic simulation studies, which revealed their binding affinities and conformational stability in the binding cavity. Thus, these derivatives may serve as lead structures for a new generation of anticancer agents.


DNA vaccines encoding membrane-bound or secreted forms of heat shock protein 70 exhibit improved potency.
Traditional vaccine strategies are inefficient against challenge with complex pathogens including HIV; therefore, novel vaccine technologies are required. DNA vaccines are attractive as they are relatively cheap and easy to manufacture, but a major limitation has been their lack of immunogenicity in humans, which may be overcome with the incorporation of an adjuvant. HSP70 is a recognised damage-associated molecular pattern, which is a potential adjuvant. We investigated the immunogenicity of a DNA vaccine encoding HIV gag and HSP70; the latter was genetically modified to produce cytoplasmic, secreted or membrane-bound HSP70, the expression of which was controlled by an independent promoter. The DNA was administered to C57BL/6 mice to evaluate gag-specific T-cell responses. Our results demonstrated the ability of membrane-bound and secreted HSP70 to significantly enhance gag-specific T-cell responses and increase the breadth of T-cell responses to include subdominant epitopes. Membrane-bound or secreted HSP70 also significantly improved the multifunctionality of HIV-specific T cells and T-cell proliferation, which is important for maintaining T-cell integrity. Most importantly, the inclusion of membrane-bound HSP70, secreted HSP70 or a combination significantly increased protection in mice challenged with EcoHIV, a chimeric virus that replicates in mouse leukocytes in vivo.


Temporal fate mapping reveals age-linked heterogeneity in naive T lymphocytes in mice.
Understanding how our T-cell compartments are maintained requires knowledge of their population dynamics, which are typically quantified over days to weeks using the administration of labels incorporated into the DNA of dividing cells. These studies present snapshots of homeostatic dynamics and have suggested that lymphocyte populations are heterogeneous with respect to rates of division and/or death, although resolving the details of such heterogeneity is problematic. Here we present a method of studying the population dynamics of T cells in mice over timescales of months to years that reveals heterogeneity in rates of division and death with respect to the age of the host at the time of thymic export. We use the transplant conditioning drug busulfan to ablate hematopoetic stem cells in young mice but leave the peripheral lymphocyte compartments intact. Following their reconstitution with congenically labeled (donor) bone marrow, we followed the dilution of peripheral host T cells by donor-derived lymphocytes for a year after treatment. Describing these kinetics with mathematical models, we estimate rates of thymic production, division and death of naive CD4 and CD8 T cells. Population-averaged estimates of mean lifetimes are consistent with earlier studies, but we find the strongest support for a model in which both naive T-cell pools contain kinetically distinct subpopulations of older host-derived cells with self-renewing capacity that are resistant to displacement by naive donor lymphocytes. We speculate that these incumbent cells are conditioned or selected for increased fitness through homeostatic expansion into the lymphopenic neonatal environment.


Long-Term Public Health Responses in High-Impact Weather Events: Hurricane Maria and Puerto Rico as a Case Study.
This statement responds to the public health challenges in Puerto Rico in the wake of Hurricane Maria during September 2017. As a result of Maria, and to a certain extent Hurricane Irma, the territory sustained unprecedented damage. We call for a mid- and long-term public health response and research to assess the long-term impacts of high-impact weather events, such as Maria's effects on Puerto Rico, including impacts on vulnerable populations' environmental health and well-being.


Minimum resolution requirements of digital pathology images for accurate classification.
Digitization of pathology has been proposed as an essential mitigation strategy for the severe staffing crisis facing most pathology departments. Despite its benefits, several barriers have prevented widespread adoption of digital workflows, including cost and pathologist reluctance due to subjective image quality concerns. In this work, we quantitatively determine the minimum image quality requirements for binary classification of histopathology images of breast tissue in terms of spatial and sampling resolution. We train an ensemble of deep learning classifier models on publicly available datasets to obtain a baseline accuracy and computationally degrade these images according to our derived theoretical model to identify the minimum resolution necessary for acceptable diagnostic accuracy. Our results show that images can be degraded significantly below the resolution of most commercial whole-slide imaging systems while maintaining reasonable accuracy, demonstrating that macroscopic features are sufficient for binary classification of stained breast tissue. A rapid low-cost imaging system capable of identifying healthy tissue not requiring human assessment could serve as a triage system for reducing caseloads and alleviating the significant strain on the current workforce.


Residential greenspace and lung function decline over 20 years in a prospective cohort: The ECRHS study.
The few studies that have examined associations between greenspace and lung function in adulthood have yielded conflicting results and none have examined whether the rate of lung function decline is affected. We explored the association between residential greenspace and change in lung function over 20 years in 5559 adults from 22 centers in 11 countries participating in the population-based, international European Community Respiratory Health Survey. Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were measured by spirometry when participants were approximately 35 (1990-1994), 44 (1999-2003), and 55 (2010-2014) years old. Greenness was assessed as the mean Normalized Difference Vegetation Index (NDVI) in 500 m, 300 m, and 100 m circular buffers around the residential addresses at the time of lung function measurement. Green spaces were defined as the presence of agricultural, natural, or urban green spaces in a circular 300 m buffer. Associations of these greenspace parameters with the rate of lung function change were assessed using adjusted linear mixed effects regression models with random intercepts for subjects nested within centers. Sensitivity analyses considered air pollution exposures. A 0.2-increase (average interquartile range) in NDVI in the 500 m buffer was consistently associated with a faster decline in FVC (-1.25 mL/year [95% confidence interval: -2.18 to -0.33]). These associations were especially pronounced in females and those living in areas with low PM10 levels. We found no consistent associations with FEV1 and the FEV1/FVC ratio. Residing near forests or urban green spaces was associated with a faster decline in FEV1, while agricultural land and forests were related to a greater decline in FVC. More residential greenspace was not associated with better lung function in middle-aged European adults. Instead, we observed slight but consistent declines in lung function parameters. The potentially detrimental association requires verification in future studies.


Effect of continuous in-feed administration of tylosin to feedlot cattle on macrolide and tetracycline resistant enterococci in a randomized field trial.
Liver abscess causes substantial economic loss to the beef cattle industry through liver condemnation, reduced animal performance, and carcass yield. Continuous in-feed use of tylosin is the most effective and a commonly used practice in beef cattle production to prevent liver abscess. However, such mass medication can increase the level of antimicrobial resistant bacteria. We investigated the effect of continuous in-feed use of tylosin in feedlot cattle on (i) concentrations and prevalence of erythromycin-resistant (ERYr) and tetracycline-resistant (TETr) enterococci; (ii) associated antimicrobial resistance genes (ARGs) for resistance; (iii) species distribution; iv) macrolide and tetracycline resistance gene concentrations; and (v) tylosin concentration. A cohort of weaned calves were randomized to receive tylosin-medicated feed (Tylosin; n = 10) or nonmedicated feed (Control; n = 10) for a full feedlot cycle. Feces, feed and pen-surface samples were collected and processed by culture, droplet digital PCR, and liquid chromatography/mass spectroscopy for bacterial enumeration, detection and characterization, ARG quantification, and tylosin concentration, respectively. Data were analyzed by mixed effects linear- or binary-regression models depending on the outcomes. Tylosin administration significantly increased fecal concentration (P < 0.001) and prevalence (P = 0.021) of ERYr enterococci and erm(B) gene concentration (P < 0.001), compared to the control group. Interestingly, tylosin administration significantly reduced (P = 0.037) fecal TETr enterococci concentration compared to the control group, with no significant effect (P = 0.758) on fecal tet(M) concentration. In both treatment groups, enterococci concentrations increased over time, peaking on 174 days in feed before returning to the baseline. ERYr enterococci concentration was significantly (P = 0.012) higher in tylosin medicated feeds, with no significant effect (P = 0.321) on TETr enterococci concentration. Pen-surface concentration of ermB was significantly (P = 0.024) higher in the tylosin group, with no significant effect (P > 0.05) on bacterial concentrations. Increased diversity and a shift in the composition of enterococcal species and ARGs were observed over time, although tylosin use did not significantly affect (P > 0.05) their prevalence. Tylosin concentration was significantly higher in the feces of tylosin administered cattle (P < 0.001) and medicated feed (P = 0.027), with numerically higher pen-surface concentration (P = 0.065) in the tylosin group. In conclusion, continuous in-feed use of tylosin in feedlot cattle increases macrolide resistant enterococci and its fecal excretion, while decreasing tetracycline resistance. Two medically important species, E. faecium and E. faecalis, were predominant regardless of resistance status or sample source. Risk-based approaches including label changes to limit tylosin use such as withdrawal period, and development of effective manure treatments are potential areas of research to reduce environmental and public health impacts.


Antimicrobial management of sepsis and septic shock.
Every patient who has sepsis and septic shock must be evaluated appropriately at presentation before the initiation of antibiotic therapy. However, in most situations, an abridged initial assessment focusing on critical diagnostic and management planning elements is sufficient. Intravenous antibiotics should be administered as early as possible, and always within the first hour of recognizing severe sepsis and septic shock. Broad-spectrum antibiotics must be selected with one or more agents active against likely bacterial or fungal pathogens and with good penetration into the presumed source. Antimicrobial therapy should be reevaluated daily to optimize efficacy, prevent resistance, avoid toxicity, and minimize costs. Consider combination therapy in septic shock Pseudomonas infections in neutropenic patients. Combination therapy should be continued for no more than 3 to 5 days and de-escalation should occur following availability of susceptibilities. The duration of antibiotic therapy typically is limited to 7 to 10 days. Longer duration is considered if response is slow, if there is inadequate surgical source control, or if immunologic deficiencies are evident. Antimicrobial therapy should be stopped if infection is not considered the etiologic factor for a shock state.


The effect of an online-supervised exercise program in older people with diabetes on fasting blood sugar, psychological resilience and quality of life: A double blind randomised controlled trial.
Online exercise interventions can improve physical outcomes. Online supervised exercise program is more effective than unsupervised exercise program. The aim of this study is to determine the effect of an online supervised exercise program on fasting blood glucose, body mass index (BMI), resilience and quality of life in older people with diabetes. This parallel group randomised controlled study included 70 older patients with Type 2 diabetes. Participants were divided into online supervised and unsupervised exercise training groups. Participants in the online-supervised exercise group were given an online-supervised exercise program 3 days a week for 6 weeks. Personal Information Form, Short Resilience Scale and Quality of Life Scale in Older People were used to collect data. In addition, fasting blood sugar BMI and values were measured. According to the results of our study, while there was no significant difference between the pre-and post-training scores of the supervised and unsupervised groups on the Psychological Resilience Scale and Quality of Life Scale, it was observed that there was a significant difference in both groups according to time (p < .05). When the difference between the scores of the groups before and after the training was analysed according to time, a significant difference was observed between the online-supervised and unsupervised exercise groups (p < .05). In addition, it was seen that there was a significant difference in the fasting blood sugar and BMI results of the online-supervised exercise group according to time (p < .05). Online supervised exercise program decreases fasting blood sugar and BMI, increases psychological resilience and quality of life of older patients with Type 2 diabetes. Online supervised exercise program may be an additional treatment that provides benefits for older people with diabetes who cannot participate in clinical-based rehabilitation programs.


Pectoralis Major Tendon Rupture While Bouldering.
Pectoralis major tendon ruptures are rare injuries. We present a case of a pectoralis major tendon rupture incurred while bouldering that required surgical repair. The diagnosis of pectoralis major tendon rupture relies predominantly on clinical examination. Among athletes, outcomes after surgical repair are superior to those after nonoperative therapy in most cases of complete tendon rupture. Although infrequent, pectoralis major tendon ruptures can occur while climbing, and early recognition and expedited surgical treatment are paramount to maximize functional recovery.


Efficacy of maintenance olaparib plus bevacizumab according to clinical risk in patients with newly diagnosed, advanced ovarian cancer in the phase III PAOLA-1/ENGOT-ov25 trial.
Adding maintenance olaparib to bevacizumab provided a significant progression-free survival (PFS) benefit in patients with newly diagnosed, advanced ovarian cancer in the randomized, double-blind PAOLA-1/ENGOT-ov25 trial (NCT02477644). We analyzed PFS by clinical risk and biomarker status. Patients received olaparib 300 mg twice daily for up to 24 months plus bevacizumab 15 mg/kg every 3 weeks for up to 15 months in total, or placebo plus bevacizumab. This post hoc exploratory analysis evaluated PFS in patients classified as higher risk (stage III with upfront surgery and residual disease or neoadjuvant chemotherapy; stage IV) or lower risk (stage III with upfront surgery and no residual disease), and by biomarker status. Of 806 randomized patients, 74% were higher risk and 26% were lower risk. After a median 22.9 months of follow-up, PFS favored olaparib plus bevacizumab versus placebo plus bevacizumab in higher-risk patients (hazard ratio [HR] 0.60; 95% confidence interval [CI] 0.49-0.74) and lower-risk patients (0.46; 0.30-0.72). Olaparib plus bevacizumab provided a substantial PFS benefit versus bevacizumab alone in the homologous recombination deficiency (HRD)-positive subgroup (higher risk: HR 0.39; 95% CI 0.28-0.54 and lower risk: 0.15; 0.07-0.30), with 24-month PFS rates in lower-risk patients of 90% versus 43%, respectively (Kaplan-Meier estimates). In PAOLA-1, maintenance olaparib plus bevacizumab provided a substantial PFS benefit in HRD-positive patients with a reduction of risk of progression or death of 61% in the higher-risk group and of 85% in the lower-risk group compared with bevacizumab alone.


Manual Therapy (Postisometric Relaxation and Joint Mobilization) in Knee Pain and Function Experienced by Patients with Rheumatoid Arthritis: A Randomized Clinical Pilot Study.
The purpose of this study was to evaluate the impact of manual therapy on the management of rheumatoid arthritis (RA) patients with knee pain. This was a small, randomized clinical pilot study. Subjects were 46 patients with diagnosed RA, randomly assigned to the manual therapy group (postisometric relaxation and joint mobilization) or control group (standard exercise). Subjects in each group had 10 sessions of interventions, once a day with one day break after the sixth day. Outcomes included the pain intensity of knee, Knee Society Score, Oxford Knee Score, and Health Assessment Questionnaire. There were no statistically significant differences between groups, except for the pain intensity of the knee. This study suggests that manual therapy (postisometric relaxation and joint mobilization) may have clinical benefits for treating knee pain and function in rheumatoid patients. Further extended studies are expected to determine the effectiveness of manual therapy in RA patients with knee pain.


Structure and receptor binding of PYY analogs.
Differences in the structure of PYY and two important analogs, PYY [3-36] and [Pro34]PYY, are evaluated. Y-receptor subtype ligand binding data are used in conjunction with structural data to develop a model for receptor subtype selective agonists. For PYY it is proposed that potent binding to Y1, Y4 and Y5 receptors requires the juxtaposition of the two termini while Y2 binding only requires the C-terminal helix. Further experiments that delineate between primary and tertiary structure contributions for receptor binding and activation are required to support the hypothesis that tertiary structure is stable enough to influence the expression of PYY's bioactivity.


Highly electrically conductive nanocomposites based on polymer-infused graphene sponges.
Conductive polymer composites require a three-dimensional 3D network to impart electrical conductivity. A general method that is applicable to most polymers for achieving a desirable graphene 3D network is still a challenge. We have developed a facile technique to fabricate highly electrical conductive composite using vacuum-assisted infusion of epoxy into graphene sponge GS scaffold. Macroscopic GSs were synthesized from graphene oxide solution by a hydrothermal method combined with freeze drying. The GS/epoxy composites prepared display consistent isotropic electrical conductivity around 1 S/m, and it is found to be close to that of the pristine GS. Compared with neat epoxy, GS/epoxy has a 12-orders-of-magnitude increase in electrical conductivity, attributed to the compactly interconnected graphene network constructed in the polymer matrix. This method can be extended to other materials to fabricate highly conductive composites for practical applications such as electronic devices, sensors, actuators, and electromagnetic shielding.


Effects of lateral wedge insole application on medial compartment knee osteoarthritis severity evaluated by ultrasound.
It is known that a lateral wedge insole (LWI) decreases medial loading stress in the knee. Medial meniscus pathology, such as a degenerative tear or a root tear, leading to malfunction and medial meniscus extrusion (MME), is a critical condition that leads to severe osteoarthritis (OA). However, the effect of LWI on MME is still unknown. The objective of this study was to investigate the effect of LWI use on MME in knee OA using ultrasonography. Thirty-one knees from 18 patients with knee OA diagnosed radiographically were allocated to the OA group (mean age, 73.6years; sex M:F, 2:16). Twenty-two knees from 11 volunteers without knee OA were also enrolled as an age-matched control group. MME was evaluated using ultrasonography with the patients in three positions: supine, standing without LWI, and standing with LWI. In both groups, the mean values of the MME increased significantly when patients were in the standing position compared to the supine position. In the OA group, MME significantly decreased with LWI use. There was no significant difference in MME between use and non-use of an LWI in the control group. The LWI could significantly decrease MME in patients with knee OA.


Divalent europium-doped near-infrared-emitting phosphor for light-emitting diodes.
Near-infrared luminescent materials exhibit unique photophysical properties that make them crucial components in photonic, optoelectronic and biological applications. As broadband near infrared phosphors activated by transition metal elements are already widely reported, there is a challenge for next-generation materials discovery by introducing rare earth activators with 4f-5d transition. Here, we report an unprecedented phosphor K3LuSi2O7:Eu2+ that gives an emission band centered at 740 nm with a full-width at half maximum of 160 nm upon 460 nm blue light excitation. Combined structural and spectral characterizations reveal a selective site occupation of divalent europium in LuO6 and K2O6 polyhedrons with small coordination numbers, leading to the unexpected near infrared emission. The fabricated phosphor-converted light-emitting diodes have great potential as a non-visible light source. Our work provides the design principle of near infrared emission in divalent europium-doped inorganic solid-state materials and could inspire future studies to further explore near-infrared light-emitting diodes.


Regulation and characterization of tumor-infiltrating immune cells in breast cancer.
The effect of immunosuppression blockade therapies depends on the infiltration of effector T cells and other immune cells in tumor. However, it is unclear how molecular pathways regulate the infiltration of immune cells, as well as how interactions between tumor-infiltrating immune cells and T cell activation affect breast cancer patient survival. CIBERSORT was used to estimate the relative abundance of 22 immune cell types. The association between mRNAs and immune cell abundance were assessed by Spearman correlation analysis. Enriched pathways were identified using MetaCore pathway analysis. The interactions between the T cell activation status and the abundance of tumor-infiltrating immune cells were evaluated using Kaplan-Meier survival and multivariate Cox regression models in a publicly available dataset of 1081 breast cancer patients. The role of tumor-infiltrating B cells in antitumor immunity, immune response of T cell subsets, and breakdown of CD4+ T cell peripheral tolerance were positively associated with M1 macrophage and CD8+ T cell but negatively associated with M2 macrophage. Abundant plasma cell was associated with prolonged survival (HR = 0.46, 95% CI: 0.32-0.67), and abundant M2 macrophage was associated with shortened survival (HR = 1.78, 95% CI: 1.23-2.60). There exists a significant interaction between the T cell activation status and the resting DC abundance level (p = 0.025). Molecular pathways associated with tumor-infiltrating immune cells provide future directions for developing cancer immunotherapies to control immune cell infiltration, and further influence T cell activation and patient survival in breast cancer.


Capturing exchange using periodic radiofrequency irradiation.
The dynamics of spin system coupled by chemical exchange between two sites with different chemical shifts during periodic radiofrequency (RF) irradiation was here investigated. When the instantaneous π-flip of effective frequency during the course of frequency sweep was applied, a significant increase of exchange-induced relaxation rate constants was observed for small tip angle of magnetization in the laboratory frame of reference. This increase of the rate constants corresponds to the side bands generated by the periodic irradiation during the RF pulses. The exchange - induced relaxation rate constants depend on the exchange conditions, the RF power and the irradiation period. The described phenomenon promises applications for studying protein dynamics and for generating exchange specific relaxation contrasts in MRI.


Personal name in Igbo Culture: A dataset on randomly selected personal names and their statistical analysis.
This data article contains the statistical analysis of Igbo personal names and a sample of randomly selected of such names. This was presented as the following: 1). A simple random sampling of some Igbo personal names and their respective gender associated with each name. 2). The distribution of the vowels, consonants and letters of alphabets of the personal names. 3). The distribution of name length. 4). The distribution of initial and terminal letters of Igbo personal names. The significance of the data was discussed.


Predictors of increased risk of adverse cardiovascular outcomes among patients with myeloproliferative neoplasms and atrial fibrillation.
Patients with myeloproliferative neoplasms (MPNs), essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), have increased risk of cardiovascular (CV) disease. Atrial fibrillation (AF) is associated with adverse CV outcomes including arterial thrombosis, heart failure (HF), and CV death and coexists with MPN. Traditional risk scores (CHA2DS2-VASC and HAS-BLED) for estimating risks/benefits of anticoagulation to prevent thrombotic events in AF do not include MPN status. Therefore, we aimed to investigate CV outcomes in patients with MPN and AF and evaluate the predictive ability of traditional risk scores. We conducted a single-center, retrospective cohort study of patients with MPN and AF. Primary outcome was composite of CV death and arterial thromboembolism; secondary outcomes were bleeding requiring emergency department visit or hospitalization, hospitalization for HF, and all-cause death. Multivariable competing-risk and Cox proportional hazards regression models were used to estimate risk of outcomes. Receiver operating characteristic (ROC) curve used to evaluate predictive ability of CHA2DS2-VASC and HAS-BLED of composite outcome and bleeding, respectively. A total 142 patients was included (62 ET, 54 PV, 26 MF). Composite outcome, bleeding, HF hospitalization and all-cause death occurred in 39 %, 30 %, 34 %, and 48 %, of patients respectively. After multivariable modeling, MF was associated with increased risk of composite outcome (SHR 2.70, 95 % CI 1.38-5.27) and all-cause mortality (HR 9.77, 95 % CI 4.88-19.54) but not bleeding (SHR 1.19, 95 % CI 0.51-2.80) or HF admissions (SHR 0.57, 95 % CI 0.19-1.72). CHA2DS2-VASC and HAS-BLED were poor predictors of composite outcome (C-statistic 0.52, 95 % CI 0.43-0.62) and bleeding (C-statistic 0.49, 95 % CI 0.40-0.58), respectively. In patients with MPN and AF, MF is associated with increased risk of CV death and arterial thrombosis and traditional risk scores do not accurately predict outcomes in this patient population. Further investigation is needed to refine risk scores in this patient population.


Correction to: Effects of Bang® Keto Coffee Energy Drink on Metabolism and Exercise Performance in Resistance-Trained Adults: A Randomized, Double-blind, Placebo-controlled, Crossover Study.
An amendment to this paper has been published and can be accessed via the original article.


Radioresistance of culture-induced augmented natural killer-like activity.
Human NK activity is radiosensitive under the control of X-linked genes. We have evaluated the expression of these genes in other forms of cellular cytotoxicity. The NK radioresistant and radiosensitive phenotype is expressed in ADCC. Specific cellular cytotoxicity, generated in a MLC with a radiosensitive donor as responder, was radioresistant. NK-like activity recruited from nonadherent cells of radiosensitive subjects stimulated with allogenic cells, mitogens (PHA, Con A or PWM), or recall antigens (TT or PPD) was radioresistant. The acquisition of radioresistance was relatively rapid, beginning within 24 hr after exposure to PHA, prior to detectable proliferation. Radioresistance of MLR augmented NK-like activity was maximal 3 days after initiation of the culture. MLR augmented NK-like activity was spared by the immunosuppressive polypeptide antibiotic CsA at doses up to 1 micrometer/ml. CsA did, however, reduce acquisition of radioresistance by the NK-like activity at doses above 0.01 mu gm/ml, a concentration which does not inhibit uptake of 3H-thymidine but does reduce the level of specific CML. These data suggest that mitogens and antigens, including allogeneic cells, are recruiting radioresistant NK-like activity which can be distinguished from the radiosensitive spontaneous NK activity of the cell donor. Further, in the MLR, both radiosensitive and radioresistant NK-like activity may be recruited.


Sod1 integrates oxygen availability to redox regulate NADPH production and the thiol redoxome.
Cu/Zn superoxide dismutase (Sod1) is a highly conserved and abundant antioxidant enzyme that detoxifies superoxide (O2•-) by catalyzing its conversion to dioxygen (O2) and hydrogen peroxide (H2O2). Using Saccharomyces cerevisiae and mammalian cells, we discovered that a major aspect of the antioxidant function of Sod1 is to integrate O2 availability to promote NADPH production. The mechanism involves Sod1-derived H2O2 oxidatively inactivating the glycolytic enzyme, GAPDH, which in turn reroutes carbohydrate flux to the oxidative phase of the pentose phosphate pathway (oxPPP) to generate NADPH. The aerobic oxidation of GAPDH is dependent on and rate-limited by Sod1. Thus, Sod1 senses O2 via O2•- to balance glycolytic and oxPPP flux, through control of GAPDH activity, for adaptation to life in air. Importantly, this mechanism for Sod1 antioxidant activity requires the bulk of cellular Sod1, unlike for its role in protection against O2•- toxicity, which only requires <1% of total Sod1. Using mass spectrometry, we identified proteome-wide targets of Sod1-dependent redox signaling, including numerous metabolic enzymes. Altogether, Sod1-derived H2O2 is important for antioxidant defense and a master regulator of metabolism and the thiol redoxome.


Comparison Between Two Volumes of 70% Alcohol in Single Injection Ultrasound-Guided Celiac Plexus Neurolysis: A Randomized Controlled Trial.
Pain due to inoperable upper abdominal malignancies is a challenging condition that needs a multimodal analgesic regimen to be managed properly. Celiac plexus alcohol neurolysis was proved to be effective in relieving such type of pain; however, there is no consistent data about the optimal volume to be used to maintain the balance between the neurolytic effect and the destructive effect of alcohol. We aim to compare the analgesic effect of 2 different volumes of alcohol to improve the outcome of interventional management. This was a randomized controlled double-blinded interventional clinical trial. Single university hospital. Thirty-two patients who suffered from abdominal pain due to unresectable abdominal malignancies were randomly allocated to receive in a single injection ultrasound-guided celiac plexus neurolysis (CPN) with injection of either 20 mL 70% alcohol (CPN20 group) or 40 mL 70% alcohol (CPN40 group). The primary outcome was the post-procedure pain score, while the secondary outcomes included the post-procedure total daily opioid consumption and quality of life (QOL). There was no statistically significant difference between both groups regarding visual analog scale (VAS) scores at all time points (P-value > 0.05); however, comparisons in each group revealed significantly reduced VAS scores at all time points following the intervention when compared to the baseline. Daily morphine equivalent consumption doses showed statistically significant differences between the baseline and each time point in both groups (P value < 0.05), with no significant difference between both groups at each time point (P value > 0.05). There was no statistically significant difference between the study groups regarding all domains in quality of life assessment at all time points (P value > 0.05). The scores of most time points in all domains were different significantly when compared to the baseline readings in both groups, with a tendency to decline over time in both groups approaching the baseline values. This was a single-center study with a relatively small sample size. Further prospective, multicenter, randomized, and controlled studies with a larger sample size are required to confirm the effects in this study. During ultrasound-guided CPN for patients with inoperable upper abdominal cancers who failed medical management, a volume of 20 mL is as effective as 40 mL of 70% alcohol regarding pain control, opioid consumption, quality of life, and procedure-related complications.


c-Src regulates constitutive and EGF-mediated VEGF expression in pancreatic tumor cells through activation of phosphatidyl inositol-3 kinase and p38 MAPK.
Multiple signaling proteins may be aberrantly activated and/or overexpressed in pancreatic tumors, including the nonreceptor protein tyrosine kinase Src. The goal of this study was to determine the role of Src in regulating VEGF expression and angiogenic potential in pancreatic cancer cell lines. Src activity was inhibited using the Src family kinase selective inhibitor PP2, and c-Src expression was down-regulated via siRNA. The activities of downstream signaling molecules phosphatidyl inositol 3'-kinase (PI3K) and p38 mitogen-activated protein kinase (MAPK) were disrupted via selective inhibitors. In vivo angiogenesis was assessed through the use of a gel-foam assay. Inhibition of Src activity or expression decreases both constitutive and EGF-induced VEGF production. Both the PI3K/Akt and p38 MAPK pathways are activated in a Src family kinase-dependent fashion on EGF-R activation and are important for EGF-mediated VEGF production in pancreatic cancer cells. Additionally, media from Src-inhibited L3.6pl cells fail to promote angiogenesis into gel foams implanted subcutaneously into mice, whereas media from control cells promote a robust angiogenic response. Src activity contributes to constitutive and EGF-induced VEGF expression and angiogenic potential in pancreatic cancer cells. Therefore, Src may be a viable target for antiangiogenesis therapy in pancreatic cancer.


Social support and stressful events in two dimensions: life events and illness as an event.
Previous research on the buffering effects of social support focused mainly on life events as stressors, and mental illness as outcome. Furthermore, the question as to why support influences illness has not been subjected to theoretical or empirical study much. In this article we develop a hypothesis on the basis of the theory of social capital. We hypothesize that specific types of social resources are more relevant to the consequences of some events than of others. We test this hypothesis in two ways: (1) by taking life events as stressor and occurrence of illness as outcome, and, which is somewhat unusual, (2) by taking illness as stressor and duration and disabilities of illness as the outcome. Analyses of a representative sample of the Dutch population (N = 10,110) reveal that receiving specific types of support does not lead to better health or less illness in cases of stress. On the contrary, people who are under stress and receive more support, also appear to report more illness, more disabilities and a longer duration. We suggest that in an open sample like ours, the disease level measured is not severe enough to assess buffer effects of social support.


A comparison of emergency department medical records to parental self-reporting of traumatic brain injury symptoms.
Studies have shown Emergency Department (ED) recording of traumatic brain injury (TBI) cases to be poor. Parents of children aged 2-12 who attended an ED with injury to the head completed a concussion checklist which was compared with medical records. ED medical records commonly used head injury (HI), concussion, minor-HI and mild-HI without distinction between TBI and superficial HI. Recalled symptoms included vomiting, blurred vision and headaches versus headaches, fatigue and feeling sick from parents who reported more concussive symptoms. More cases of TBI were identifiable from parental recall compared with medical records, which recorded fewer symptoms for diagnosis, prognosis and statistical reporting of TBI. Clear guidelines need to be implemented to improve retrospective diagnosis for incidence gathering and future clinical use.


Predicting sediment yield on different landuse surfaces in Calabar River Catchment, Nigeria.
This study predicts sediment yield on various landuse surfaces within the Calabar River Catchment, Nigeria. Five experimental plots of 31 by 23 cm (representing urban, farm, grass, bare, and forest surfaces) were established on a convex slope series with a 20% gradient, oriented along the slope strike. Rainfall, morphological, and hydraulic stations were derived for each plot. Multiple regressions and Factor analysis were employed to analyse the collected data. The research identifies critical factors influencing sediment yield, such as rainfall amount, rainfall intensity, slope gradient, slope length, sand, silt, clay, vegetation cover, and infiltration capacity. The results (p < 0.05) indicate that slope length, sand, silt, clay, infiltration capacity, and vegetation cover significantly influence sediment yield for urban, farmland, grassland, and bare surfaces, respectively. Factor analysis revealed strong correlations between sediment yield, silt, rainfall amount, rainfall intensity, and slope gradient. Case-wise diagnostics predictions indicate sediment yields for urban, bare, farm, grass, and vegetation-covered surfaces as 14.95 kg, 33.91 kg, 28.78 kg, 33.50 kg, and 5.66 kg, respectively. The regression model, with case-wise diagnostic residual statistics and standard prediction coefficients, provides valuable insights. For example, the forest surface exhibited a minimum sediment yield of -1.413 kg/m2 with each unit decrease in forest area, emphasising the significance of vegetation cover in sediment retention. Conversely, bare surfaces showed a maximum sediment yield of 0.843 kg/m2 with each unit increase in bare surface area, highlighting their heightened vulnerability to sediment erosion. Considering the implications of these findings, the development of urban master plans that incorporate well-designed landscaping and drainage systems is crucial, particularly in high rainfall catchments like the study area. Such measures can effectively mitigate sediment yield and address the adverse effects of land use changes on different surfaces.


Overcoming a travel burden to high-volume centers for treatment of retroperitoneal sarcomas is associated with improved survival.
Guidelines recommend treatment of retroperitoneal sarcomas (RPS) at high-volume centers. However, high-volume centers may not be accessible locally. This national study compared outcomes of RPS resection between local low-volume centers and more distant high-volume centers. Patients treated for RPS were identified from the National Cancer Database (1998-2012). Travel distance and annual hospital volume were divided into quartiles. Two groups were identified: (1) short travel to low-volume hospitals (ST/LV), (2) long travel to high-volume hospitals (LT/HV). Outcomes were adjusted for clinical, tumor, and treatment characteristics. Two thousand five hundred ninety-nine patients met the inclusion criteria. The LT/HV cohort was younger and more often white (p < 0.01). The LT/HV group had more comorbidities, higher tumor grade, and more often radical resections and radiotherapy (all p < 0.05). The ST/LV group underwent significantly more R2 resections (4.4% vs. 2.6%, p = 0.003). Thirty-day mortality was significantly lower in the LT/HV group (1.2% vs. 2.8%, p = 0.0026). Five-year survival was better among the LT/HV group (63% vs. 53%, p < 0.0001). After adjustment, the LT/HV group had a 27% improvement in overall survival (HR 0.73, p = 0.0009). This national study suggests that traveling to high-volume centers for the treatment of RPS confers a significant short-term and long-term survival advantage, supporting centralized care for RPS.


Long-Acting Therapies Will Expand Growth Hormone Deficiency Market.
Future therapies for growth hormone deficiency are expected to include long-acting formulations that may encourage increased use of and adherence to these products.


[Invasion patterns and metastasis of urothelial carcinoma. A challenge for translational research].
Local invasion of cancer cells occurs early during the progression of urothelial carcinoma. Micrometastatic disease and the presence of nodal metastases are major causes of cancer-specific mortality following radical surgery. Only surrogate markers for aggressive and micrometastatic disease have been identified. The metastatic cascade is complex, including multiple steps from initial invasion to colonization and proliferation at distant sites. The initial mechanisms of cancer cell dissemination in urothelial carcinoma are poorly understood. Various proteases, chemokines and growth factors are involved in this process and alterations of the lymphatic system may promote systemic spread. There is a high demand for therapeutic targeting of the metastatic process. Functional preclinical studies in representative models are therefore required to better elucidate the multiple steps of progression. We review the current knowledge on factors associated with metastasis in urothelial carcinoma. Preclinical approaches to identify key player molecules for invasion and to develop new therapeutic strategies are discussed.


Current Radiographic Iodinated Contrast Agents.
Millions of radiologic examinations requiring the use of iodinated contrast are performed yearly in North America. Triiodobenzoic acid, the contrast agent molecule currently in use, is a benzene ring covalently bonded to the 3 iodine atoms. Iodinated contrast media can be divided in 4 categories: ionic monomers, ionic dimers, nonionic monomer, and nonionic dimers. Currently, second- and third-generation nonionic low-osmolar and iso-osmolar contrast media are used in clinical practice. The search for a safer and more effective iodinated contrast agents remains an ongoing challenge and important research topic.


Evaluating the physicochemical properties of refuse with a short-term landfill age and odorous pollutants emission during landfill mining: A case study.
A field excavation of refusewitha short-termlandfillage from the Qingdao Xiaojianxi municipal solid waste (MSW) landfill was conducted. The physical composition and chemical properties of refuse with landfill ages of 1-4 years were studied, and the emission characteristics of odorous pollutants during the excavation period were monitored. The refuse aged 1-2 years has a higher proportion of combustible material than that the refuse aged 3-4 years, and the volatile content and calorific value in refuse aged 1-2 years were also higher than those in refuse aged 3-4 years, indicating that the refuse with a short-term landfill age was more suitable for incineration than refuse with a long-term landfill age. The pH and availablephosphorus (AP) gradually increased with increasing landfill age, while the total Kjeldahlnitrogen (TKN) and organic matter (OM) decreased. The contents of the heavy metals Cu, Zn, Ni, Pb and As generally decreased with landfill age, especially in refuse aged 2-4 years, whereas the Cr content showed no significant differences in refuse aged 1-4 years. The main odorous pollutants emitted during the excavation and screening periods were ammonia (NH3) and carbon disulfide (CS2), and the odor intensity of excavated refuse aged 1-3 years was higher than that of refuse aged 4 years. Under the condition of a small excavation area and continuous deodorization, the pollution intensity can meet the discharge standards of the factory boundary.


Put your board on high alert for Sarbanes-Dxley 'Creep'.
The law was aimed at for-profit boards, but it's having an increasingly big impact on how not-for-profit hospital trustees do their work.


Treatment of various types of basal cell carcinoma with topical 5% imiquimod in the elderly who refused surgical intervention: a case series.
Basal cell carcinoma (BCC) is the most common non-melanoma skin cancer in the elderly population, causing significant local destruction and image deformities. Although surgical excision is the primary treatment modality, preservation of functions, cosmetic concerns and patient's age, as well as tumor prognostic factors, aid in treatment selection. Topical imiquimod provides immunomodulatory effects by increasing the release of proinflammatory cytokines, and is currently approved and funded for pathologically diagnosed superficial BCC. We report herein the successful results of topical imiquimod in four cases of BCC, nodular and large superficial types, all of whom refused surgical intervention. The lesions regressed in all except one in whom more than one BCC of superficial type was present. She is still on follow-up for intermittent cryotherapy sessions. Imiquimod is a good alternative to surgery in elderly patients who have unwillingness to surgery and are often poor candidates for surgery.


Eukaryotic phosphatase inhibitors enhance colistin efficacy in gram-negative bacteria.
The mounting threat of multi-drug-resistant (MDR) bacteria places a tremendous strain on the antimicrobial clinical arsenal, forcing physicians to revert to near-obsolete antibiotics to treat otherwise intractable infections. Antibiotic adjuvant therapy has emerged as a viable alternative to the development of novel antimicrobial agents. This method uses combinations of an existing antibiotic and a non-antimicrobial small molecule, where the combination either breaks drug resistance or further potentiates antibiotic activity. Through a high-content screen of eukaryotic kinase inhibitors, our group previously identified two highly potent adjuvants that synergize with colistin, a cyclic, polycationic antimicrobial peptide that serves as a drug of last resort for the treatment of MDR Gram-negative bacterial infections. Cell signaling proteins implicated in colistin resistance mechanisms display both kinase and phosphatase activities. Herein, we explore the potential for eukaryotic phosphatase inhibitors to be repurposed as colistin adjuvants. From a panel of 48 unique structures, we discovered that the natural product kuwanon G breaks colistin resistance, while the non-antimicrobial macrolide ascomycin potentiates colistin in polymyxin-susceptible bacteria.


Effects of bestatin on phagocytic cells in cyclophosphamide-treated mice.
The low-molecular weight dipeptide bestatin is a potent inhibitor of aminopeptidase N and has been demonstrated to have antitumor and immunomodulatory effects. The effects of bestatin on interleukin (IL)-1β synthesis and release by peritoneal macrophages stimulated in vitro with lipopolysaccharide (LPS) from E. coli, the phagocytic and oxidative burst activity from peripheral blood monocytes and granulocytes and the number of blood leukocytes and blood picture in cyclophosphamide-treated mice were tested. Bestatin at doses of 1 and 0.1 mg/kg was injected into cyclophosphamide-treated mice ip five times on alternating days or ten times at 24 h intervals. The first dose of bestatin was administered 24 h after a single injection of cyclophosphamide at a dose of 350 mg/kg. It was found that bestatin administered at doses of 1 and 0.1 mg/kg five times on alternating days increased the synthesis and release of IL-1β by resident peritoneal murine macrophages stimulated in vitro with LPS in cyclophosphamide-treated mice. The immunocorrecting action of bestatin on the picture of peripheral blood in cyclophosphamide-treated mice was primarily observed with young forms of neutrophilic granulocytes. The changes were observed irrespective of the dosage and the number of subsequent doses applied. Moreover, the administration of bestatin after pharmacological immunosuppression partially prevented the suppressive effects of cyclophosphamide on the oxidative burst activity of peripheral blood monocytes and stimulated the phagocytic activity of granulocytes.


Predicting recurrence after curative resection for gastric cancer: External validation of the Italian Research Group for Gastric Cancer (GIRCG) prognostic scoring system.
Most nomograms for Gastric Cancer (GC) were developed to predict overall survival (OS) after curative resection. The Italian Research Group for Gastric Cancer (GIRCG) prognostic scoring system (PSS) was designed to predict the recurrence risk after curative treatment based on pathologic tumor stage and treatment performed (D1-D2/D3 lymphadenectomy). This study was carried out to externally validate the GIRCG's PSS. Adopting the same criteria used by GIRCG to build the PSS, 185 patients with GC operated with curative intention were selected. The median follow-up period was 77.8 months (1.93-150.8) for all patients and 102.5 months (60.9-150.8) for patients free of disease. The NRI (net reclassification improvement) was calculated to estimate the overall improvement in the reclassification of patients using the PSS in place of the TNM stage system. GC recurrence occurred in 70 (37.8%) patients. The mean time to recurrence was 22.2 (range 1.9-98.1) months. For patients with recurrence, the gain in the proportion of reclassification was 0.257 (p < 0.001), indicating an improvement of 26%. For patients without recurrence, the gain in the proportion of reclassification was -0.122 (p < 0.001), indicating a worsening of 12%. The NRI calculated was 0.135 (p = 0.0527). The GIRCG's PSS, which predicts the likelihood of recurrence after radical surgical treatment for GC, is more accurate than TNM system to predict recurrence mainly for high-risk patients. Yet, the PSS does not have the same effectiveness for low-risk patients, overestimating the chance of recurrence occurs even for disease-free patients.


Statistical Analysis in the German National Cohort (NAKO) - Specific Aspects and General Recommendations.
The German National Cohort (NAKO) is an ongoing, prospective multicenter cohort study, which started recruitment in 2014 and includes more than 205,000 women and men aged 19-74 years. The study data will be available to the global research community for analyses. Although the ultimate decision about the analytic methods will be made by the respective investigator, in this paper we provide the basis for a harmonized approach to the statistical analyses in the NAKO. We discuss specific aspects of the study (e.g., data collection, weighting to account for the sampling design), but also give general recommendations which may apply to other large cohort studies as well.


miR-552 promotes the proliferation and metastasis of intrahepatic cholangiocarcinoma by targeting FOXO1.
Intrahepatic cholangiocarcinoma (ICC) is a relatively rare but highly malignant cancer. Few effective systemic targeted therapies are available for patients with unresectable ICC, but there exists an urgent need to explore mechanisms underlying the initiation and progression of ICC. MicroRNA (miRNA) plays vital roles in the initiation, progression, and drug resistance of different cancers. Recently, the biological function of a novel miRNA, miR-552, has been widely analyzed in hepatocellular carcinoma and colorectal, cervical, gastric, and other cancers. However, its role in ICC has not yet been elucidated. In this study, we found that miR-552 expression was upregulated in ICC and that miR-552 predicted poor prognosis. Using functional studies, we found that miR-552 enhanced the proliferation and invasion ability of ICC cells. Mechanistic research identified that forkhead box O1 (FOXO1) is the target of miR-552 in ICC. Moreover, the combined panels of miR-552 and FOXO1 exhibited a better prognostic value for ICC patients than did miR-552 alone. In conclusion, these findings demonstrated that the miR-552/FOXO1 axis drove ICC progression, further suggesting that targeting this axis could be a novel therapeutic strategy for ICC.


Cardiac structure and function before and after bariatric surgery: a clinical overview.
Obesity, defined as a body mass index of ≥30 kg/m2 , is the most common chronic metabolic disease worldwide and its prevalence has been strongly increasing. Obesity has deleterious effects on cardiac function. The purpose of this review is to evaluate the effects of obesity and excessive weight loss due to bariatric surgery on cardiac function, structural changes and haemodynamic responses of both the left and right ventricle.


Idiopathic pneumonia syndrome with thrombotic microangiopathy-related changes after allogeneic hematopoietic stem cell transplantation.
Idiopathic pneumonia syndrome (IPS), defined as widespread alveolar injury, is a severe complication of hematopoietic stem cell transplantation (HSCT) and a clinical syndrome with variable histopathologic correlates and multiple etiologies. Transplantation-associated thrombotic microangiopathy (TMA) is another severe complication of HSCT. TMA occurs when endothelial injury causes thrombosis and fibrin deposition in the organ microcirculation. We present a case of IPS with TMA-related changes in the lungs following HSCT. A 54-year-old woman underwent an allogeneic HSCT for refractory multiple myeloma. During transplantation, cyclosporine was administered for prophylaxis against graft-versus-host disease, but she developed respiratory failure after she was weaned off the drug. A computed tomography scan revealed ground-glass attenuation and reticular opacity in the bilateral whole-lung fields. Bronchoscopy indicated no evidence of infection, and IPS was diagnosed. High-dose steroids and etanercept were ineffective, and she died 1 month after the onset of IPS. Autopsy revealed diffuse alveolar damage, and stenosis or obstruction due to intimal thickening and thrombi resulting from endothelial injury in the arterioles of both lungs. We retrospectively diagnosed TMA based on the histological and clinical findings. To our knowledge, this is the first report suggesting the possible role of TMA in the clinical course of IPS.


Drivers of variability in Blue Carbon stocks and burial rates across European estuarine habitats.
The implementation of climate change mitigation strategies based on the conservation and restoration of Blue Carbon ecosystems requires a deep understanding of the magnitude and variability in organic carbon (Corg) storage across and within these ecosystems. This study explored the variability in soil Corg stocks and burial rates across and within intertidal estuarine habitats of the Atlantic European coast and its relation to biotic and abiotic drivers. A total of 136 soil cores were collected across saltmarshes located at different tidal zones (high marsh, N = 45; low marsh, N = 30), seagrass meadows (N = 17) and tidal flats (N = 44), and from the inner to the outer sections of five estuaries characterized by different basin land uses. Soil Corg stocks were higher in high-marsh communities (65 ± 3 Mg ha-1) than in low-marsh communities (38 ± 3 Mg ha-1), seagrass meadows (40 ± 5 Mg ha-1) and unvegetated tidal flats (46 ± 3 Mg ha-1) whereas Corg burial rates also tended to be higher in high marshes (62 ± 13 g m-2 y-1) compared to low marshes (43 ± 15 g m-2 y-1) and tidal flats (35 ± 9 g m-2 y-1). Soil Corg stocks and burial rates decreased from inner to outer estuarine sections in most estuaries reflecting the decrease in the river influence towards the estuary mouth. Higher soil Corg stocks were related to higher content of silt and clay and higher proportion of forest and natural land within the river basin, pointing at new opportunities for protecting coastal natural carbon sinks based on the conservation and restoration of upland ecosystems. Our study contributes to the global inventory of Blue Carbon by adding data from unexplored regions and habitats in Europe, and by identifying drivers of variability across and within estuaries.


Radical reirradiation for recurrent or second primary carcinoma of the female reproductive tract.
Twenty-five women have been treated with a second course of irradiation for recurrent cancer or a second primary carcinoma arising within a previously irradiated pelvic volume. Fourteen patients have been rendered cancer-free (56%) with follow-up ranging from 10 to 61 months. Three of these patients have died of intercurrent disease. Seven of these patients have experienced major complications (50%), necessitating surgical intervention in three cases. The rationale for reirradiation and techniques of retreatment are discussed. Prognostic factors are analyzed and criteria for patient selection are identified.


Catecholamines may play an important role in the pathogenesis of transient mid- and basal ventricular ballooning syndrome.
The exact pathogenesis of transient mid- and basal ventricular ballooning, a new variant of transient left ventricular (LV) ballooning, remains unknown. We report two cases of transient mid- and basal ventricular ballooning associated with catecholamines. These cases suggest that catecholamine-mediated myocardial dysfunction might be a potential mechanism of this syndrome.


Compact program resolves overlapping voltammetric peaks.
A simple self-contained program designed to separate overlapping peaks from electrochemical analyses is presented. Combining an original interactive way to define initial parameter estimates with nonlinear curve fitting based on the simplex method of optimization, it allows the user to resolve voltammograms consisting of 2 to 5 analytical peaks raised on a straight base line. The program provides highly intuitive interface, easy operation, and straightforward result documentation. A free package including the program, three data files and user instructions is available on request.


Novel Connections of Common Childhood Illnesses Based on More Than 5 Million Diary Registrations From Birth Until Age 3 Years.
All children experience numerous episodes of illness during the first 3 years of life. Most episodes are mild and handled without medical attention but nevertheless burden the families and society. There is a large, and still unexplained, variation in the burden of illness between children. To describe and provide a better understanding of the disease burden of common childhood diseases through a data-driven approach investigating the communalities between symptom patterns and predefined variables on predispositions, pregnancy, birth, environment, and child development. The study is based on the prospectively followed clinical mother-child cohort COpenhagen Prospective Studies on Asthma in Childhood, which includes 700 children with daily symptom registration in the first 3 years of life, including symptoms of cough, breathlessness, wheeze, cold, pneumonia, sore throat, ear infections, gastrointestinal infections, fever, and eczema. First, we described the number of episodes of symptoms. Next, factor analysis models were used to describe the variation in symptom load in the second year of life (both based on n = 556, with >90% complete diary). Then we characterized patterns of similarity between symptoms using a graphical network model (based on n = 403, with a 3-year monthly compliance of >50%). Finally, predispositions and pregnancy, birth, environmental, and developmental factors were added to the network model. The children experienced a median of 17 (interquartile range, 12-23) episodes of symptoms during the first 3 years of life, of which most were respiratory tract infections (median, 13; interquartile range, 9-18). The frequency of symptoms was the highest during the second year of life. Eczema symptoms were unrelated to the other symptoms. The strongest association to respiratory symptoms was found for maternal asthma, maternal smoking during the third trimester, prematurity, and CDHR3 genotype. This was in contrast to the lack of associations for the well-established asthma locus at 17q21. Healthy young children are burdened by multiple episodes of symptoms during the first 3 years of life. Prematurity, maternal asthma, and CDHR3 genotype were among the strongest drivers of symptom burden.


Advanced analytical tools in proteomics.
Proteomics deals with the study of proteins, their structures, localizations, posttranslational modifications, functions and interactions with other proteins. The mapping of protein structure-function holds the key to a better understanding of cellular functions under both normal and disease states, which is critical for modern drug discovery. However, the study of human proteome presents scientists with a task much more daunting than the human genome project. In fact, the estimated >100,000 different proteins expressed from 30,000 to 40,000 human genes make it extremely challenging, if not impossible with existing protein analysis techniques, to map the entire cellular functions at the translational level. Consequently, there have been rapid advances in the techniques and methods capable of large-scale proteomic studies. Among them, the recently developed high-throughput screening methods have enabled scientists to analyze proteins quickly and efficiently at an organism-wide scale. Herein, we overview some of these emerging tools for high-throughput protein analysis. In particular, we focus on recent advances in the bioassay development, which has provided sensitive and selective tools for high-throughput identification and characterizations of enzymes. Finally, the recently developed bioimaging techniques to visualize and quantify proteins in living cells are also discussed.


CT values in orbital hydatid cyst.
The CT values of 15 cases of orbital hydatid cyst operated upon by the author were reviewed. It was found that hydatid cyst of the orbit has high CT value, contrary to the low CT value of nonorbital hydatid. This discrepancy was confirmed by an experiment using human skull and two balls simulating hydatid cyst. One ball was put in the orbit and the other in the cranial cavity. When the skull was CT scanned it was found that the orbital ball CT value was about five times higher than the cranial ball, in spite of the fact that both balls had the same content. It was concluded that the orbital bony pyramid is the cause of this high CT value in orbital hydatid. Hence it is recommended that an orbital lesion with a high CT value can be a hydatid cyst.


Factor V G1691A (Leiden) and prothrombiG20210A gene mutation status, and thrombosis in patients with chronic myeloproliferative disorders.
The aim of this study was to examine Factor V G1691A (Leiden) (FVL) and prothrombin G20210A (PT) gene mutation status, and their relationship with thrombosis in patients with chronic myeloproliferative disorders (CMPDs). The study included 160 patients with a CMPD that were regularly followed-up between 1993 and 2009. FVL and PT mutation status was established based on blood samples analyzed via PCR using specific primers. The frequency of FVL and PT mutation was 12.5% and 4.4%, respectively. In total, 27 episodes of thrombosis occurred in 24 (15%) of the patients, and there wasn't an association between the observed thrombotic events, and FVL or PT mutations. Hepatic vein thrombosis was noted in 3 patients that had FVL mutation, of which 1 also had PT mutation. We did not observe a relationship between thrombosis, and FVL or PT mutations in CMPD patients; however, 3 of the patients that had hepatic vein thrombosis also had FVL mutation. Larger studies are needed to more clearly determine if all CMPD patients with hepatic vein thrombosis need be investigated for FVL and PT mutation.


Complications and Mortality in Chronic Renal Failure Patients Undergoing Total Joint Arthroplasty: A Comparison Between Dialysis and Renal Transplant Patients.
In total joint arthroplasty (TJA) literature, there is a paucity of large cohort studies comparing chronic kidney disease (CKD) and end-stage renal disease (ESRD) vs non-CKD/ESRD patients. Thus, the purposes of this study were (1) to identify inhospital complications and mortality in CKD/ESRD and non-CKD/ESRD patients and (2) compare inhospital complications and mortality between dialysis and renal transplantation patients undergoing TJA. We queried the Nationwide Inpatient Sample database for patients with and without diagnosis of CKD/ESRD and those with a renal transplant or on dialysis undergoing primary or revision total knee or hip arthroplasty from 2007 to 2011. Patient comorbidities were identified using the Elixhauser comorbidity index. International Classification of Diseases, Ninth Revision, codes were used to identify postoperative surgical site infections (SSIs), wound complications, deep vein thrombosis, and transfusions. Chronic kidney disease/ESRD was associated with greater risk of SSIs (odds ratio [OR], 1.4; P<.001), wound complications (OR, 1.1; P=.01), transfusions (OR, 1.6; P<.001), deep vein thrombosis (OR, 1.4; P=.03), and mortality (OR, 2.1; P<.001) than non-CKD/ESRD patients. Dialysis patients had higher rates of SSI, wound complications, transfusions, and mortality compared to renal transplant patients. Chronic kidney disease/ESRD patients had a greater risk of SSIs and wound complications compared to those without renal disease, and the risk of these complications was even greater in CKD/ESRD patients receiving dialysis. These findings emphasize the importance of counseling CKD patients about higher potential complications after TJA, and dialysis patients may be encouraged to undergo renal transplantation before TJA.


Immunosuppression in patients with grade 3 acute-on-chronic liver failure at transplantation: A practice analysis study.
Transplantation for patients with acute-on-chronic liver failure grade 3 (ACLF3) has encouraging results with 1-year-survival of 80-90%. These patients with multiple organ failure meet the conditions for serious alterations of drug metabolism and increased toxicity. The goal of this study was to identify immunosuppression-dependent factors that affect survival. This retrospective monocentric study was conducted in patients with ACLF3 consecutively transplanted between 2007 and 2019. The primary endpoint was 1-year survival. Secondary endpoints were overall survival, treated rejection, and surgical complications. Immunosuppression was evaluated as to type of immunosuppression, post-transplant introduction timing, trough levels, and trough level intra-patient variability (IPV). One hundred patients were included. Tacrolimus IPV < 40% (P = .019), absence of early tacrolimus overdose (P = .033), use of anti-IL2-receptor antibodies (P = .034), and early mycophenolic acid introduction (P = .038) predicted 1-year survival. Treated rejection was an independent predictor of survival (P = .001; HR 4.2 (CI 95%: 1.13-15.6)). Early everolimus introduction was neither associated with higher rejection rates nor with more surgical complications. Management of immunosuppression in ACLF3 critically ill patients undergoing liver transplantation is challenging. Occurrence and treatment of rejection impacts on survival. Early introduction of mTOR inhibitor seems safe and efficient in this situation.


An exploratory study on online quantification of isoprene in human breath using cavity ringdown spectroscopy in the ultraviolet.
Breath analysis offers a promising method of noninvasive analyses of volatile metabolites and xenobiotics present in human body. Isoprene is one of the highest abundant volatile organic compounds (VOCs) present in human exhaled breath. Breath isoprene (50-200 part per billion by volume (ppbv) or higher) can be analyzed by using mass spectroscopy-based methods, yet laser absorption spectral detection of breath isoprene has not been much reported, partially due to its ultraviolet (UV) absorption wavelength and the spectral overlap with other breath VOCs such as acetone in the same wavelength region. These facts make it challenging to develop a spectroscopy-based breath isoprene analyzer for a potential portable instrument. Here we report on the development of a cavity ringdown spectroscopy (CRDS) system for detection of breath isoprene in the UV region near 226 nm. First, we investigated spectral absorption interferences near 226 nm and selected an optimal detection wavelength at 226.56 nm with minimum to no spectral interference. We then measured absorption cross-sections of isoprene at 225.5-227.4 nm under controlled cavity pressures, and the measured absorption cross-section 1.93 × 10-17 cm2/molecule at 226.56 nm was used to quantify isoprene in different cases including human breath gas samples. Finally, we validated the CRDS system by measuring breath gas samples from 19 human subjects using proton transfer reaction mass spectrometry (PTR-MS). The CRDS system shows good linear response (R2 = 0.999), high stability (0.2%), and high accuracy (R2 = 0.906 with PTR-MS). The limit of detection of the system was 0.47 ppbv, with average over 100 ringdown events (equivalent to 5 s). This work represents the first exploratory study of the detection of breath isoprene using CRDS. The results demonstrate the potential of developing a CRDS-based breath analyzer for online, near-real time, sensitive analysis of breath isoprene for further research that would help to elucidate its physiological and clinical significance.


Alveolar volume determined by single-breath helium dilution correlates with the high-resolution computed tomography-derived nonemphysematous lung volume.
The alveolar volume (V(A)), determined by single-breath helium dilution, is a measure for the total lung capacity (TLC) that is very sensitive to ventilatory disturbances. In chronic obstructive pulmonary disease (COPD), the emphysematous lung parts are less accessible to test gas; therefore, the V(A) is smaller than TLC measured by multiple-breath helium dilution (TLC(He)). The aim of this study was to investigate whether the V(A) represents the nonemphysematous lung parts. We measured V(A) as part of the diffusing capacity for carbon monoxide (DL(CO)), TLC(He) and spirometry in 50 patients with COPD. High-resolution computed tomography (HRCT) scans of all subjects were analyzed with the density mask method, where parts with an attenuation of less than -950 Hounsfield units were considered as emphysematous. A strong correlation was observed between the V(A) (mean 5.2 liters) and nonemphysematous HRCT lung volume (mean 5.2 liters, r(2) = 0.9) and between the TLC(He) (mean 6.6 liters) and total HRCT lung volume (mean 6.4 liters, r(2) = 0.9). Bland-Altman plots showed considerable disagreement between the V(A) and the nonemphysematous HRCT lung volume. A weak correlation between the forced expiratory volume in 1 s (mean 46% predicted) and DL(CO) (mean 46% predicted) versus the HRCT emphysema ratio (nonemphysematous/total HRCT lung volume) was observed (r(2) = 0.3 and 0.3, respectively). We concluded that the V(A) correlates with the nonemphysematous HRCT lung volume, although the two measurements are not equivalent, possibly due to technical factors.


Prevalence, Microbiological Profile, and Risk Factors of Surgical Site Infections in Saudi Patients with Colorectal Cancer.
Resection surgery in patients with colorectal cancer (CRC) patients is associated with potential complications, including surgical site infection (SSI). To estimate the prevalence rate of SSI, identify the common pathogens responsible for SSI, and determine potential risk factors for SSI development in a cohort from Saudi Arabia. Patients with CRC who underwent bowel resection surgery at King Abdulaziz Medical City, Riyadh, between January 01, 2016, and December 31, 2019, were retrospectively included. Demographics, comorbidities, surgical procedure data, and the results of preoperative laboratory tests were retrospectively collected from medical records through the health information system. The study population was divided into two groups: those who developed SSI and those who did not. A total of 92 patients with CRC who underwent resection surgery were included, of which 54 (58.7%) were males. The median age was 65 (IQR 55.5-75.0) years. SSI was observed in 25 (27.2%) patients. The most frequently isolated organisms were Escherichia coli and Pseudomonas aeruginosa, followed by Klebsiella pneumoniae, vancomycin-sensitive Enterococcus faecium, and methicillin-resistant Staphylococcus aureus. Three E. coli isolates were producers of extended-spectrum beta-lactamases, and two K. pneumoniae isolates exhibited a multidrug resistance profile. Low preoperative serum albumin level was identified as a significant independent risk factor for developing SSI (AOR = 0.853, 95% CI = 0.748-0.973, P = 0.0181). The study found a notable prevalence of SSI among the included patients. Gram-negative bacteria were more involved in SSI events and were also associated with drug-resistance patterns. Gut microbiota bacteria were most commonly involved in SSIs. Low preoperative serum albumin levels predicted the development of postoperative SSI, and thus its close monitoring and management before surgery could reduce the SSIs.