Epidemiology and aetiology of marathon running injuries.
Over the last 10-15 years, there has been a dramatic increase in popularity of running marathons. Numerous articles have reported on injuries to runners of all experience, with yearly incidence rates for injury reported to be as high as 90% in those training for marathons. To date, most of these studies have been cohort studies and retrospective surveys with remarkably few prospective studies. However, from the studies available, it is clear that more experienced runners are less prone to injury, with the number of years running being inversely related to incidence of injuries. For all runners, it is important to be fully recovered from any and all injury or illness prior to running a marathon. For those with less experience, a graduated training programme seems to clearly help prevent injuries with special attention to avoid any sudden increases in running load or intensity, with a particularly high risk for injury once a threshold of 40 miles/week is crossed. In both sexes, the most common injury by far was to the knee, typically on the anterior aspect (e.g. patellofemoral syndrome). Iliotibial band friction syndrome, tibial stress syndrome, plantar fasciitis, Achilles tendonitis and meniscal injuries of the knee were also commonly cited.


Urban waste flows and their potential for a circular economy model at city-region level.
To enable cities to become more circular, i.e. close material cycles, decision-makers need detailed data about the production and treatment of waste. At city level, conventional statistics on waste are often incomplete or lack detail. Waste input-output accounting offers an alternative, using waste supply and use tables to create detailed inventories of economy-wide flows of waste. In this study we develop such tables for the city-region of Brussels (Belgium) and use them to analyse the urban waste metabolism in terms of waste flows, waste production intensity and waste treatment performance. The waste flow analysis revealed: the amount of collected waste; the proportion contributed by individual sectors; the material composition of waste flows and the location of treatment. Currently, around 50% of the 1.5 million tons of waste collected in Brussels is treated in local facilities. However, less than 1% of the collected waste is used in a way that closes material cycles within city limits. The waste performance analysis reveals that the construction sector had the highest waste production intensity and the household sector the highest incineration intensity. In terms of waste prevention and local valorisation potential, we identified flows and sectors for future targeting, one of the most promising being food waste. We conclude that the urban context can restrict the local valorisation of waste flows, thus we see the role of cities such as Brussels in a circular economy as mainly contributing to the closing of material cycles at national or even global level.


The molecular basis of synergism between carboplatin and ABT-737 therapy targeting ovarian carcinomas.
Resistance to standard chemotherapy (carboplatin + paclitaxel) is one of the leading causes of therapeutic failure in ovarian carcinomas. Emergence of chemoresistance has been shown to be mediated in part by members of the Bcl family of proteins including the antiapoptotic protein Bcl-x(L), whose expression is correlated with shorter disease-free intervals in recurrent disease. ABT-737 is an example of one of the first small-molecule inhibitors of Bcl-2/Bcl-x(L) that has been shown to increase the sensitivity of ovarian cancer cells to carboplatin. To exploit the therapeutic potential of these two drugs and predict optimal doses and dose scheduling, it is essential to understand the molecular basis of their synergistic action. Here, we build and calibrate a mathematical model of ABT-737 and carboplatin action on an ovarian cancer cell line (IGROV-1). The model suggests that carboplatin treatment primes cells for ABT-737 therapy because of an increased dependence of cells with DNA damage on Bcl-x(L) for survival. Numerical simulations predict the existence of a threshold of Bcl-x(L) below which these cells are unable to recover. Furthermore, co- plus posttreatment of ABT-737 with carboplatin is predicted to be the best strategy to maximize synergism between these two drugs. A critical challenge in chemotherapy is to strike a balance between maximizing cell-kill while minimizing patient drug load. We show that the model can be used to compute minimal doses required for any desired fraction of cell kill. These results underscore the potential of the modeling work presented here as a valuable quantitative tool to aid in the translation of novel drugs such as ABT-737 from the experimental to clinical setting and highlight the need for close collaboration between modelers and experimental scientists.


Total knee arthroplasties from the origin to navigation: history, rationale, indications.
Since the early 1970s, total knee arthroplasties have undergone many changes in both their design and their surgical instrumentation. It soon became apparent that to improve prosthesis durability, it was essential to have instruments which allowed them to be fitted reliably and consistently. Despite increasingly sophisticated surgical techniques, preoperative objectives were only met in 75% of cases, which led to the development, in the early 1990s, in Grenoble (France), of computer-assisted orthopaedic surgery for knee prosthesis implantation. In the early 2000s, many navigation systems emerged, some including pre-operative imagery ("CT-based"), others using intra-operative imagery ("fluoroscopy-based"), and yet others with no imagery at all ("imageless"), which soon became the navigation "gold standard". They use an optoelectronic tracker, markers which are fixed solidly to the bones and instruments, and a navigation workstation (computer), with a control system (e.g. pedal). Despite numerous studies demonstrating the benefit of computer navigation in meeting preoperative objectives, such systems have not yet achieved the success they warrant, for various reasons we will be covering in this article. If the latest navigation systems prove to be as effective as the older systems, they should give this type of technology a well-deserved boost.


Host density increases parasite recruitment but decreases host risk in a snail-trematode system.
Most species aggregate in local patches. High host density in patches increases contact rate between hosts and parasites, increasing parasite transmission success. At the same time, for environmentally transmitted parasites, high host density can decrease infection risk to individual hosts, because infective stages are divided among all hosts in a patch, leading to safety in numbers. We tested these predictions using the California horn snail, Cerithideopsis californica (=Cerithidea californica), which is the first intermediate host for at least 19 digenean trematode species in California estuaries. Snails become infected by ingesting trematode eggs or through penetration by free-swimming miracidia that hatch from trematode eggs deposited with final-host (bird or mammal) feces. This complex life cycle decouples infective-stage production from transmission, raising the possibility of an inverse relationship between host density and infection risk at local scales. In a field survey, higher snail density was associated with increased trematode (infected snail) density, but decreased trematode prevalence, consistent with either safety in numbers, parasitic castration, or both. To determine the extent to which safety in numbers drove the negative snail-density-trematode-prevalence association, we manipulated uninfected snail density in 83 cages at eight sites within Carpinteria Salt Marsh (California, USA). At each site, we quantified snail density and used data on final-host (bird and raccoon) distributions to control for between-site variation in infective-stage supply. After three months, overall trematode infections per cage increased with snail biomass density. For egg-transmitted trematodes, per-snail infection risk decreased with snail biomass density in the cage and surrounding area, whereas per-snail infection risk did not decrease for miracidium-transmitted trematodes. Furthermore, both trematode recruitment and infection risk increased with infective-stage input, but this was significant only for miracidium-transmitted species. A model parameterized with our experimental results and snail densities from 524 field transects estimated that safety in numbers, when combined with patchy host density, halved per capita infection risk in this snail population. We conclude that, depending on transmission mode, host density can enhance parasite recruitment and reduce per capita infection risk.


Nutritional status of young children with inherited blood disorders in western Kenya.
To determine the association between a range of inherited blood disorders and indicators of poor nutrition, we analyzed data from a population-based, cross-sectional survey of 882 children 6-35 months of age in western Kenya. Of children with valid measurements, 71.7% were anemic (hemoglobin < 11 g/dL), 19.1% had ferritin levels < 12 μg/L, and 30.9% had retinol binding protein (RBP) levels < 0.7 μmol/L. Unadjusted analyses showed that compared with normal children, homozygous α(+)-thalassemia individuals had a higher prevalence of anemia (82.3% versus 66.8%, P = 0.001), but a lower prevalence of low RBP (20.5% versus 31.4%, P = 0.024). In multivariable analysis, homozygous α(+)-thalassemia remained associated with anemia (adjusted odds ratio [aOR] = 1.8, P = 0.004) but not with low RBP (aOR = 0.6, P = 0.065). Among young Kenyan children, α(+)-thalassemia is associated with anemia, whereas G6PD deficiency, haptoglobin 2-2, and HbS are not; none of these blood disorders are associated with iron deficiency, vitamin A deficiency, or poor growth.


Evaluation of a Distance Education Course Using the 4C-ID Model for Continuing Endodontics Education.
Continuing professional development (CPD) is needed in endodontics, and distance learning environments and courses may be preferable for CPD. Instructional designs (IDs) have been reported to strongly influence the educational effectiveness of these courses. Four Component Instructional Design (4C-ID) is an ID found to be effective for distance learning. The aim of this study was to evaluate the effectiveness of a distance learning CPD course on regenerative endodontic procedures (REPs) designed with a 4C-ID model. The study was conducted between April 2017 and March 2018 with volunteers from the 2015-16 graduates of Selçuk University's Faculty of Dentistry in Turkey. Pre- and posttests and skill assessment guide were used for assessment. To determine the participants' satisfaction levels, the Satisfaction Scale for e-Learning Process and an open-ended question were used. Of the 86 graduates invited to participate, 79.1% (n=68) responded they would; but the investigators limited the participants to 30, and the first 30 volunteers who had identified a need for REPs CPD were accepted to the course. Four (0.13%) had to drop out during the course, so data from the 26 who completed it were evaluated. The findings showed the difference between pre- and posttest results was significant (p<0.001). The mean score for psychomotor skills at the end of the course was 99.62±1.96 out of 100. On the satisfaction scale, the mean score for all participants was 138.5 on a scale from 29=lower satisfaction to 145=greater satisfaction with the e-learning process. At the end of the REPs course, the participants' knowledge levels had increased, and they were able to apply REP steps on a model. These results suggest the 4C-ID was effective in this distance education course in REPs.


Hydrate nucleation and growth on water droplets acoustically-levitated in high-pressure natural gas.
Hydrate formation was studied using water droplets acoustically levitated in high-pressure natural gas. Despite the absence of solid interfaces, the droplets' area-normalised nucleation rate was about four times faster than in steel autoclave measurements with interfacial areas roughly 200 times larger. Multiple stages of stochastic, template-free hydrate growth were observed.


Psychosocial Vulnerabilities to Upper Respiratory Infectious Illness: Implications for Susceptibility to Coronavirus Disease 2019 (COVID-19).
For 35 years, our laboratory has been involved in identifying psychosocial factors that predict who becomes ill when they are exposed to a virus affecting the upper respiratory tract. To pursue this question, we used a unique viral-challenge design in which we assessed behavioral, social, and psychological factors in healthy adults. We subsequently exposed these adults to a cold or influenza virus and then monitored them in quarantine for 5 to 6 days for onset of respiratory illness. Factors we found to be associated with greater risk of respiratory illnesses after virus exposure included smoking, ingesting an inadequate level of vitamin C, and chronic psychological stress. Those associated with decreased risk included social integration, social support, physical activity, adequate and efficient sleep, and moderate alcohol intake. We cautiously suggest that our findings could have implications for identifying who becomes ill when exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). This argument is based on evidence that the associations we report are replicable across multiple respiratory viruses and that the pathways found to link psychosocial factors to colds and influenza may play similar roles in COVID-19.


Professional Music Training and Novel Word Learning: From Faster Semantic Encoding to Longer-lasting Word Representations.
On the basis of previous results showing that music training positively influences different aspects of speech perception and cognition, the aim of this series of experiments was to test the hypothesis that adult professional musicians would learn the meaning of novel words through picture-word associations more efficiently than controls without music training (i.e., fewer errors and faster RTs). We also expected musicians to show faster changes in brain electrical activity than controls, in particular regarding the N400 component that develops with word learning. In line with these hypotheses, musicians outperformed controls in the most difficult semantic task. Moreover, although a frontally distributed N400 component developed in both groups of participants after only a few minutes of novel word learning, in musicians this frontal distribution rapidly shifted to parietal scalp sites, as typically found for the N400 elicited by known words. Finally, musicians showed evidence for better long-term memory for novel words 5 months after the main experimental session. Results are discussed in terms of cascading effects from enhanced perception to memory as well as in terms of multifaceted improvements of cognitive processing due to music training. To our knowledge, this is the first report showing that music training influences semantic aspects of language processing in adults. These results open new perspectives for education in showing that early music training can facilitate later foreign language learning. Moreover, the design used in the present experiment can help to specify the stages of word learning that are impaired in children and adults with word learning difficulties.


Quantitative Phenotyping of Xenopus Embryonic Heart Pathophysiology Using Hemoglobin Contrast Subtraction Angiography to Screen Human Cardiomyopathies.
Congenital heart disease (CHD) is a significant cause of mortality in infants and adults. Currently human genomic analysis has identified a number of candidate genes in these patients. These genes span diverse categories of gene function suggesting that despite the similarity in cardiac lesion, the underlying pathophysiology may be different. In fact, patients with similar CHDs can have drastically different outcomes, including a dramatic decrease in myocardial function. To test these human candidate genes for their impact on myocardial function, we need efficient animals models of disease. For this purpose, we paired Xenopus tropicalis with our microangiography technique, hemoglobin contrast subtraction angiography (HCSA). To demonstrate the gene-teratogen-physiology relationship, we modeled human cardiomyopathy in tadpoles. First we depleted the sarcomeric protein myosin heavy chain 6 (myh6) expression using morpholino oligos. Next, we exposed developing embryos to the teratogen ethanol and in both conditions showed varying degrees of cardiac dysfunction. Our results demonstrate that HCSA can distinguish biomechanical phenotypes in the context of gene dysfunction or teratogen. This approach can be used to screen numerous candidate CHD genes or suspected teratogens for their effect on cardiac function.


Measured parental weight status and familial socio-economic status correlates with childhood overweight and obesity at age 9.
Parental obesity is a predominant risk factor for childhood obesity. Family factors including socio-economic status (SES) play a role in determining parent weight. It is essential to unpick how shared family factors impact on child weight. This study aims to investigate the association between measured parent weight status, familial socio-economic factors and the risk of childhood obesity at age 9. Cross sectional analysis of the first wave (2008) of the Growing Up in Ireland (GUI) study. GUI is a nationally representative study of 9-year-old children (N = 8,568). Schools were selected from the national total (response rate 82%) and age eligible children (response rate 57%) were invited to participate. Children and their parents had height and weight measurements taken using standard methods. Data were reweighted to account for the sampling design. Childhood overweight and obesity prevalence were calculated using International Obesity Taskforce definitions. Multinomial logistic regression examined the association between parent weight status, indicators of SES and child weight. Overall, 25% of children were either overweight (19.3%) or obese (6.6%). Parental obesity was a significant predictor of child obesity. Of children with normal weight parents, 14.4% were overweight or obese whereas 46.2% of children with obese parents were overweight or obese. Maternal education and household class were more consistently associated with a child being in a higher body mass index category than household income. Adjusted regression indicated that female gender, one parent family type, lower maternal education, lower household class and a heavier parent weight status significantly increased the odds of childhood obesity. Parental weight appears to be the most influential factor driving the childhood obesity epidemic in Ireland and is an independent predictor of child obesity across SES groups. Due to the high prevalence of obesity in parents and children, population based interventions are required.


2-Butoxyethanol from cleaning products responsible for complaints in workplaces: a case study.
Indoor air quality is important because people are spending an increasing amount of time in the workplace. They are exposed to outdoor pollutants as well as pollutants emitted from products used indoors. Some chemicals, belonging to the category of volatile organic compounds (VOCs), easily release vapors at room temperature by evaporation. These accumulated vapors are often toxic and irritating. They may be alcohols, glycols, ketones, esters, etc., frequently present in the composition of many products for personal care or household purposes. This study suggests that the exposure levels of 2-butoxyethanol play an important role in the level of complaints of people at work. This study has emphasized the necessity of using different active and passive sampling methods for indoor air to avoid evaluation errors.


Prevention of venous thromboembolism amongst patients in an acute tertiary referral teaching public hospital: a best practice implementation project.
Deep vein thrombosis and pulmonary embolism are known collectively as venous thromboembolism (VTE). These conditions are possible complications in hospitalized patients that can extend hospital stay, result in unplanned readmission, and are associated with long-term disability and death. Despite strong evidence, many patients do not receive optimal thromboprophylaxis. VTE prevention is a top priority in healthcare systems worldwide. The aim of the project was to establish a standardized hospital-wide VTE prevention program and to improve awareness of, and compliance with, best practice standards in the prevention of VTE. A multidisciplinary team utilized the Joanna Briggs Institute Practical Application of Clinical Evidence System program to facilitate the collection of pre and post implementation audit data. The Getting Research into Practice program was also used to conduct a situational analysis to identify barriers, enablers, and implementation strategies while taking into account the context in which the changes were to occur. Hospital-acquired VTE data were collected to monitor the impact, if any, on patient outcomes. The project was conducted in three different phases over a 2.5-year period in an acute care public hospital. A comprehensive suite of professionally crafted guidelines, tools, and resources were developed to facilitate clinician acceptance of evidence-based practices. Comparison of compliance results showed variable improvements with four audit criteria. Formalized patient risk assessment improved to 7.5% with the introduction of a new form. High-risk patients receiving appropriate prophylaxis improved to 81% in medical and 83% in surgical patients, on an existing high background compliance rate. A total of 59% of staff attended a VTE update education in-service. No patients received information about adverse VTE events prior to discharge. The hospital-acquired VTE rate decreased slightly from 0.65 to 0.52 events per 1000 overnight bed days. Overall the project achieved improvements in compliance with best practice standards. A number of delays and barriers contributed to some of the planned interventions not being fully implemented at the time of the follow-up audit. Contributing factors included the lack of electronic capabilities, some processes not being fully embedded into routine clinical workflows, lack of staff time, and identification of an additional organizational barrier relating to practical issues in providing patient education at discharge. A second action cycle is recommended in an attempt to further improve compliance, ensure intervention fidelity, and embed practices into routine daily workflows to positively impact patient and organizational outcomes.


Progress and prospects for stem cell engineering.
Stem cells offer tremendous biomedical potential owing to their abilities to self-renew and differentiate into cell types of multiple adult tissues. Researchers and engineers have increasingly developed novel discovery technologies, theoretical approaches, and cell culture systems to investigate microenvironmental cues and cellular signaling events that control stem cell fate. Many of these technologies facilitate high-throughput investigation of microenvironmental signals and the intracellular signaling networks and machinery processing those signals into cell fate decisions. As our aggregate empirical knowledge of stem cell regulation grows, theoretical modeling with systems and computational biology methods has and will continue to be important for developing our ability to analyze and extract important conceptual features of stem cell regulation from complex data. Based on this body of knowledge, stem cell engineers will continue to develop technologies that predictably control stem cell fate with the ultimate goal of being able to accurately and economically scale up these systems for clinical-grade production of stem cell therapeutics.


The development of soviet optics and spectroscopy during the past fifty years.
A history of Soviet spectroscopy is given, with special emphasis on various areas indicating the earliest workers in each specialty and their principal successors; for example, the work of Rozhdestvenskii (anomalous dispersion); Fok (self-consistant field calculations), Terenin (photochemistry, atomic beams), Mandelstam (combination scattering), Vavilov (luminescence, quantum properties of light), Cerenkov (radiation), Chaika (atomic lifetimes), Gross (excitons), and Volkenstein (molecular vibrations).


With the "universal definition," measurement of creatine kinase-myocardial band rather than troponin allows more accurate diagnosis of periprocedural necrosis and infarction after coronary intervention.
We aimed to assess the differential implications of creatine kinase-myocardial band (CK-MB) and troponin measurement with the universal definition of periprocedural injury after percutaneous coronary intervention. Differentiation between definitions of periprocedural necrosis and periprocedural infarction has practical, sociological, and research implications. Troponin is the recommended biomarker, but there has been debate about the recommended diagnostic thresholds. Thirty-two patients undergoing multivessel percutaneous coronary intervention and late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging in a prospective study had cardiac troponin I, CK-MB, and inflammatory markers (C-reactive protein, serum amyloid A, myeloperoxidase, tumor necrosis factor alpha) measured at baseline, 1 h, 6 h, 12 h, and 24 h after the procedure. Three "periprocedural injury" groups were defined with the universal definition: G1: no injury (biomarker <99th percentile); G2: periprocedural necrosis (1 to 3 × 99th percentile); G3: myocardial infarction (MI) type 4a (>3 × 99th percentile). Differences in inflammatory profiles were analyzed. With CK-MB there were 17, 10, and 5 patients in groups 1, 2, and 3, respectively. Patients with CK-MB-defined MI type 4a closely approximated patients with new CMR-LGE injury. Groups defined with CK-MB showed progressively increasing percentage change in C-reactive protein and serum amyloid A, reflecting increasing inflammatory response (p < 0.05). Using cardiac troponin I resulted in 26 patients defined as MI type 4a, but only a small minority had evidence of abnormality on CMR-LGE, and only 3 patients were defined as necrosis. No differences in inflammatory response were evident when groups were defined with troponin. Measuring CK-MB is more clinically relevant for diagnosing MI type 4a, when applying the universal definition. Current troponin thresholds are oversensitive with the arbitrary limit of 3 × 99th percentile failing to discriminate between periprocedural necrosis and MI type 4a. (Myocardial Injury following Coronary Artery bypass Surgery versus Angioplasty: a randomised controlled trial using biochemical markers and cardiovascular magnetic resonance imaging; ISRCTN25699844).


The feasibility of single-incision video-assisted thoracoscopic major pulmonary resection performed by surgeons experienced with a two-incision technique.
This study evaluated the safety and feasibility of a single-incision video-assisted thoracoscopic surgery (VATS) major pulmonary resection performed by surgeons experienced with the two-incision technique. Consecutive patients who underwent single-incision VATS major pulmonary resection from March 2012 to May 2013 were included. The fifth intercostal space was incised (3-5 cm) at the anterior or posterior axillary line according to the tumour location. In total, 60 patients (39 men, 21 women; median age, 61 years; interquartile range, 53-69 years) were included in this study. Malignant lung disease was diagnosed preoperatively in 56 patients (93%) and benign disease in 4 (7%) patients. Lobectomy was performed in the majority of patients (n = 55), bilobectomy in 1, sleeve lobectomy in 1 and segmentectomy in 3. Four patients (7%) required a second incision, and conversion to thoracotomy was required in 2 (3%). In 50 lung cancer cases completed using a single-incision technique, the median surgical duration was 145 min (interquartile range, 90-182 min), and the total number of dissected lymph nodes per patient was 22 (interquartile range, 10-28 min). The chest tube was removed 5 days (interquartile range, 3-6 days) postoperatively, and there were no cases involving major perioperative morbidity or mortality. Single-incision VATS major pulmonary resection is feasible, and following a two-incision technique learning period, may yield results similar to those obtained with conventional VATS lobectomy.


Evaluation of hemostatic analytes after use of hypertonic saline solution combined with colloids for resuscitation of dogs with hypovolemia.
The effects of hypertonic saline solution (HTSS) combined with colloids on hemostatic analytes were studied in 15 dogs. The analytes evaluated included platelet counts, one-stage prothrombin time, activated partial thromboplastin time, von Willebrand's factor antigen (vWf:Ag), and buccal mucosa bleeding times. The dogs were anesthetized, and jugular phlebotomy was used to induced hypovolemia (mean arterial blood pressure = 50 mm of Hg). Treatment dogs (n = 12) were resuscitated by infusion (6 ml/kg of body weight) of 1 of 3 solutions: HTSS combined with 6% dextran 70, 6% hetastarch, or 10% pentastarch. The control dogs (n = 3) were autotransfused. Hemostatic analytes were evaluated prior to induction of hypovolemia (baseline) and then after resuscitation (after 30 minutes of sustained hypovolemia) at 0.25, 0.5, 1, 6 and 24 hours. All treatment dogs responded rapidly and dramatically to resuscitation with hypertonic solutions. Clinically apparent hemostatic defects (epistaxis, petechiae, hematoma) were not observed in any dog. All coagulation variables evaluated, with the exception of vWf:Ag, remained within reference ranges over the 24-hour period. The vWf:Ag values were not statistically different than values from control dogs, and actual values were only slightly lower than reference ranges. Significant (P < or = 0.04) differences were detected for one-stage prothrombin time, but did not exceed reference ranges. The results of this study suggested that small volume HTSS/colloid solutions do not cause significant alterations in hemostatic analytes and should be considered for initial treatment of hypovolemic or hemorrhagic shock.


[Is psoriasis a dependent cardiovascular risk factor?].
Psoriasis is a chronic inflammatory skin disease that affects approximately 2% of the Dutch population. It has been hypothesized that chronic inflammation occurring in psoriasis patients is more than skin deep, resulting in increased cardiovascular risk. Some observational studies have confirmed this association, although increased cardiovascular risk may also be explained by an increased prevalence of unhealthy life-style factors, systemic medication, the presence of psoriatic arthritis and detection bias. Based on the currently available evidence, we note that the current studies are insufficient to prove that psoriasis has a direct and independent effect on cardiovascular risk. Therefore, suggestions to change the cardiovascular screening and care of psoriasis patients seem to be a step too far. This hypothesis must first be investigated in specifically designed cohort studies or randomized controlled trials.


Selective Inhibition of 2-Oxoglutarate and 2-Oxoadipate Dehydrogenases by the Phosphonate Analogs of Their 2-Oxo Acid Substrates.
Phosphonate analogs of pyruvate and 2-oxoglutarate are established specific inhibitors of cognate 2-oxo acid dehydrogenases. The present work develops application of this class of compounds to specific in vivo inhibition of 2-oxoglutarate dehydrogenase (OGDH) and its isoenzyme, 2-oxoadipate dehydrogenase (OADH). The isoenzymes-enriched preparations from the rat tissues with different expression of OADH and OGDH are used to characterize their interaction with 2-oxoglutarate (OG), 2-oxoadipate (OA) and the phosphonate analogs. Despite a 100-fold difference in the isoenzymes ratio in the heart and liver, similar Michaelis saturations by OG are inherent in the enzyme preparations from these tissues ( K m O G = 0.45 ± 0.06 and 0.27 ± 0.026 mM, respectively), indicating no significant contribution of OADH to the OGDH reaction, or similar affinities of the isoenzymes to OG. However, the preparations differ in the catalysis of OADH reaction. The heart preparation, where OADH/OGDH ratio is ≈ 0.01, possesses low-affinity sites to OA ( K m O A = 0.55 ± 0.07 mM). The liver preparation, where OADH/OGDH ratio is ≈ 1.6, demonstrates a biphasic saturation with OA: the low-affinity sites ( K m , 2 O A = 0.45 ± 0.12 mM) are similar to those of the heart preparation; the high-affinity sites ( K m , 1 O A = 0.008 ± 0.001 mM), revealed in the liver preparation only, are attributed to OADH. Phosphonate analogs of C5-C7 dicarboxylic 2-oxo acids inhibit OGDH and OADH competitively to 2-oxo substrates in all sites. The high-affinity sites for OA are affected the least by the C5 analog (succinyl phosphonate) and the most by the C7 one (adipoyl phosphonate). The opposite reactivity is inherent in both the low-affinity OA-binding sites and OG-binding sites. The C6 analog (glutaryl phosphonate) does not exhibit a significant preference to either OADH or OGDH. Structural analysis of the phosphonates binding to OADH and OGDH reveals the substitution of a tyrosine residue in OGDH for a serine residue in OADH among structural determinants of the preferential binding of the bulkier ligands to OADH. The consistent kinetic and structural results expose adipoyl phosphonate as a valuable pharmacological tool for specific in vivo inhibition of the DHTKD1-encoded OADH, a new member of mammalian family of 2-oxo acid dehydrogenases, up-regulated in some cancers and associated with diabetes and obesity.


Endovascular treatment of unruptured wide-necked intracranial aneurysms: comparison of dual microcatheter technique and stent-assisted coil embolization.
Endovascular treatment of wide-necked aneurysms is challenging. Stent-assisted coiling (SAC) is associated with increased complications and requires dual antiplatelet therapy. To compare treatment of unruptured, wide-necked aneurysms with a dual-microcatheter technique (DMT) versus SAC. Between 2006 and 2011, 100 patients with unruptured wide-necked intracranial aneurysms were treated with DMT and 160 with SAC. Over time there was a significant decrease in the use of SAC and a corresponding increase in DMT. The investigators matched 60 patients treated with DMT blinded to outcome in a 1:2 fashion based on maximal aneurysm dome diameter with 120 patients treated with SAC. Outcomes were determined with conditional (matched) multivariate analysis. There were no significant differences in patient or aneurysm characteristics between cohorts, including aneurysm diameter, neck width, or volume. Overall packing density and coil volume achieved was not significantly different between cohorts. There were higher rates of overall complications in those receiving SAC (19.2%) compared with DMT (5.0%; p=0.012), but no significant difference in major complications (8.3% vs 1.7%, respectively; p=0.103). At a mean follow-up of 27.0 ± 18.9 months, rates of retreatment did not differ between DMT (15.1%) and SAC (17.7%). Delayed in-stent stenosis occurred in five patients and in-stent thrombosis in four patients treated with SAC. There was no difference in favorable functional outcome (modified Rankin score 0-2) between those treated with DMT (90.6%) compared with SAC (91.2%). DMT and SAC are effective endovascular approaches for unruptured, wide-necked aneurysms; however, DMT may result in less morbidity. Further long-term studies are necessary to determine the optimal indications for these treatment options.


Reliable non-invasive measurement of human neurochemistry using proton spectroscopy with an anatomically defined amygdala-specific voxel.
Given the central role of the amygdala in fear perception and expression and its likely abnormality in affective disorders and autism, there is great demand for a technique to measure differences in neurochemistry of the human amygdala. Unfortunately, it is also a technically complex target for magnetic resonance spectroscopy (MRS) due to a small volume, high field inhomogeneity and a shared boundary with hippocampus, which can undergo opposite changes in response to stress. We attempted to achieve reliable PRESS-localized single-voxel MRS at 3T of the isolated human amygdala by using anatomy to guide voxel size and location. We present data from 106 amygdala-MRS sessions from 58 volunteers aged 10 to 52 years, including two tests of one-week stability and a feasibility study in an adolescent sample. Our main outcomes were indices of spectral quality, repeated measurement variability (within- and between-subject standard deviations), and sensitivity to stable individual differences measured by intra-class correlation (ICC). We present metrics of amygdala-MRS reliability for n-acetyl-aspartate, creatine, choline, myo-Inositol, and glutamate+glutamine (Glx). We found that scan quality suffers an age-related difference in field homogeneity and modified our protocol to compensate. We further identified an effect of anatomical inclusion near the endorhinal sulcus, a region of high synaptic density, that contributes up to 29% of within-subject variability across 4 sessions (n=14). Remaining variability in line width but not signal-to-noise also detracts from reliability. Statistical correction for partial inclusion of these strong neurochemical gradients decreases n-acetyl-aspartate reliability from an intraclass correlation of 0.84 to 0.56 for 7-minute acquisitions. This suggests that systematic differences in anatomical inclusion can contribute greatly to apparent neurochemical concentrations and could produce false group differences in experimental studies. Precise, anatomically-based prescriptions that avoid age-related sources of inhomogeneity and use longer scan times may permit study of individual differences in neurochemistry throughout development in this late-maturing structure.


Controlled human infection for vaccination against Streptococcus pyogenes (CHIVAS): Establishing a group A Streptococcus pharyngitis human infection study.
Group A Streptococcus (GAS) is a highly-adapted and human-restricted pathogen responsible for a high global burden of disease across a diverse clinical spectrum. Vaccine development has been impeded by scientific, regulatory, and commercial obstacles. Human infection studies (HIS) are increasingly contributing to drug, diagnostics, and vaccine development, reducing uncertainty at early stages, especially for pathogens with animal models that incompletely reproduce key elements of human disease. We review the small number of historical GAS HIS and present the study protocol for a dose-ranging inpatient study in healthy adults. The primary objective of the study is to establish a new GAS pharyngitis HIS with an attack rate of at least 60% as a safe and reliable platform for vaccine evaluation and pathogenesis research. According to an adaptive dose-ranging study design, emm75 GAS doses manufactured in keeping with principles of Good Manufacturing Practice will be directly applied by swab to the pharynx of carefully screened healthy adult volunteers at low risk of severe complicated GAS disease. Participants will remain as closely monitored inpatients for up to six days, observed for development of the primary outcome of acute symptomatic pharyngitis, as defined by clinical and microbiological criteria. All participants will be treated with antibiotics and followed as outpatients for six months. An intensive sampling schedule will facilitate extensive studies of host and organism dynamics during experimental pharyngitis. Ethics approval has been obtained and the study has been registered at ClinicalTrials.gov (NCT03361163).


Contextualizing CBPR: Key Principles of CBPR meet the Indigenous research context.
This paper addresses two questions regarding the use of Community-based Participatory Research (CBPR) approaches with tribal communities. First, how do "gold standard" CBPR principles hold up when applied to Native American communities and what additional contextual information is necessary to understand and work with these principles in this setting? Second, what additional principles or recommendations are helpful for researchers interested in conducting research using a CBPR approach with tribal communities? We studied a variety of literature sources on CBPR and Native health research to answer these questions. We are unaware of any publications that contextualize CBPR principles for working with specific populations. This information has direct application for conducting research with tribal communities, and confirms the importance of using CBPR approaches in this setting.


Characterization of Mineralocorticoid Receptor Antagonist Therapy Initiation in High-Risk Patients With Heart Failure.
Heart failure guidelines recommend routine monitoring of serum potassium, and renal function in patients treated with a mineralocorticoid receptor antagonist (MRA). How these recommendations are implemented in high-risk patients or according to setting of drug initiation is poorly characterized. We conducted a retrospective cohort study of Medicare beneficiaries linked to laboratory data in 10 states with prevalent heart failure as of July 1, 2011, and incident MRA use between May 1 and September 30, 2011. Outcomes included laboratory testing before MRA initiation and in the early (days 1-10) and extended (days 11-90) post-initiation periods, based on setting of drug initiation and the presence of renal insufficiency. Additional outcomes included abnormal laboratory results and adverse events proximate to MRA initiation. Of 10 443 Medicare beneficiaries with heart failure started on an MRA, 19.7% were initiated during a hospitalization. Appropriate follow-up laboratory testing across all time periods occurred in 25.2% of patients with inpatient initiation compared with 2.8% of patients begun as an outpatient. Patients with chronic kidney disease had higher rates of both hyperkalemia and acute kidney failure in the early (1.3% and 2.7%, respectively) and extended (5.6% and 9.8%, respectively) post-initiation periods compared with those without chronic kidney disease. Patients initiated on MRA therapy as an outpatient had extremely poor rates of guideline indicated follow-up laboratory monitoring after drug initiation. In particular, patients with chronic kidney disease are at high risk for adverse events after MRA initiation. Quality improvement initiatives focused on systems to improve appropriate laboratory monitoring are needed.


Shear wave elastography of passive skeletal muscle stiffness: influences of sex and age throughout adulthood.
Numerous structural and compositional changes - related not only to age, but also activity level and sex - may affect skeletal muscle stiffness across the adult age-span. Measurement techniques available thus far have largely limited passive stiffness evaluations to those of entire joints and muscle-tendon units. Shear wave elastography is an increasingly popular ultrasound technique for evaluating the mechanical properties of skeletal muscle tissue. The purpose of this study was to quantify the passive stiffness, or shear modulus, of the biceps brachii throughout adulthood in flexed and extended elbow positions. We hypothesized that shear modulus would be higher in males relative to females, and with advanced age in both sexes. Shear wave elastography quantified biceps brachii stiffness at 90° elbow flexion and full extension in a large sample of adults between 21 and 94 years old (n=133; 47 males). Regression analysis found sex and age were significant parameters for older adults (>60 years) in full extension. As expected, shear modulus values increased with advancing age; however, shear modulus values for females tended to be higher than those for males. This study begins to establish normative trends for skeletal muscle shear modulus throughout adulthood. Specifically, this work establishes for the first time that the higher passive joint torque often found in males relative to females likely relates to parameters other than muscle shear modulus. Indeed, perhaps increases in skeletal muscle passive stiffness, though potentially altering the length-tension curve, serve a protective role - maintaining the tendon-muscle-tendon length-tension curve within a functional range.


Multiple forms of sheep serum A-esterase activity associated with the high-density lipoprotein.
Five lipoproteins of sheep serum expressing A-esterase activity, but with differing activities towards four organophosphate substrates, were separated by a combination of gel filtration and ion-exchange chromatography. Each had an Mr of approx. 360,000 and contained a major peptide of Mr 28,000-30,000 that appeared to be present as several isoforms on urea/agarose isoelectric focusing. In every case this peptide split into a number of bands on urea/agarose isoelectric focusing. The bands appear to represent isoforms of the peptide, and four lipoproteins yielded characteristic patterns of bands. This peptide resembles the apolipoprotein A-I of human serum, and available evidence suggests that this is the protein that expresses A-esterase activity. Evidence is presented for the existence of different species of high-density lipoprotein HDL2 particles containing different complements of peptide isoforms and expressing contrasting substrate specificities towards organophosphates.


Neurodevelopmental outcomes at age 5 among children born preterm: EPIPAGE-2 cohort study.
To describe neurodevelopment at age 5 among children born preterm. Population based cohort study, EPIPAGE-2. France, 2011. 4441 children aged 5½ born at 24-26, 27-31, and 32-34 weeks MAIN OUTCOME MEASURES: Severe/moderate neurodevelopmental disabilities, defined as severe/moderate cerebral palsy (Gross Motor Function Classification System (GMFCS) ≥2), or unilateral or bilateral blindness or deafness, or full scale intelligence quotient less than minus two standard deviations (Wechsler Preschool and Primary Scale of Intelligence, 4th edition). Mild neurodevelopmental disabilities, defined as mild cerebral palsy (GMFCS-1), or visual disability ≥3.2/10 and <5/10, or hearing loss <40 dB, or full scale intelligence quotient (minus two to minus one standard deviation) or developmental coordination disorders (Movement Assessment Battery for Children, 2nd edition, total score less than or equal to the fifth centile), or behavioural difficulties (strengths and difficulties questionnaire, total score greater than or equal to the 90th centile), school assistance (mainstream class with support or special school), complex developmental interventions, and parents' concerns about development. The distributions of the scores in contemporary term born children were used as reference. Results are given after multiple imputation as percentages of outcome measures with exact binomial 95% confidence intervals. Among 4441 participants, 3083 (69.4%) children were assessed. Rates of severe/moderate neurodevelopmental disabilities were 28% (95% confidence interval 23.4% to 32.2%), 19% (16.8% to 20.7%), and 12% (9.2% to 14.0%) and of mild disabilities were 38.5% (33.7% to 43.4%), 36% (33.4% to 38.1%), and 34% (30.2% to 37.4%) at 24-26, 27-31, and 32-34 weeks, respectively. Assistance at school was used by 27% (22.9% to 31.7%), 14% (12.1% to 15.9%), and 7% (4.4% to 9.0%) of children at 24-26, 27-31, and 32-34 weeks, respectively. About half of the children born at 24-26 weeks (52% (46.4% to 57.3%)) received at least one developmental intervention which decreased to 26% (21.8% to 29.4%) for those born at 32-34 weeks. Behaviour was the concern most commonly reported by parents. Rates of neurodevelopment disabilities increased as gestational age decreased and were higher in families with low socioeconomic status. In this large cohort of children born preterm, rates of severe/moderate neurodevelopmental disabilities remained high in each gestational age group. Proportions of children receiving school assistance or complex developmental interventions might have a significant impact on educational and health organisations. Parental concerns about behaviour warrant attention.


Night Shift Work, Chronotype, Sleep Duration, and Prostate Cancer Risk: CAPLIFE Study.
To analyze the association between prostate cancer (PCa) risk and night shift work, chronotype, and sleep duration in the context of a population-based case-control study of incident prostate cancer in Spain, a total of 465 PCa cases and 410 controls were analyzed. Selection criteria were: (i) age 40-80 years, and (ii) residence in the coverage area of the reference hospitals for ≥6 months before recruitment. Exposure variables were: (i) night shift work (permanent or rotating); (ii) chronotype: morning, neither, or evening (Munich ChronoType Questionnaire) and (iii) sleep duration according to the recommendations of the American National Sleep Foundation. PCa aggressiveness was determined according to the International Society of Urology Pathology classification. Adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) were estimated using logistic regression models. Night shift work was associated with PCa, aOR = 1.47 (95% CI 1.02-2.11), especially for rotating night shifts, aOR = 1.73 (95% CI 1.09-2.75). The magnitude of the association between ever night work and PCa was higher in evening subjects with aOR = 3.14 (95% CI 0.91-10.76) than in morning chronotypes with an aOR = 1.25 (95% CI 0.78-2.00). Working night shifts, especially rotating night shifts, could increase PCa risk. This risk may be higher in people with an evening chronotype.


Comparison of quality of life after stereotactic body radiotherapy and surgery for early-stage prostate cancer.
As the long-term efficacy of stereotactic body radiation therapy (SBRT) becomes established and other prostate cancer treatment approaches are refined and improved, examination of quality of life (QOL) following prostate cancer treatment is critical in driving both patient and clinical treatment decisions. We present the first study to compare QOL after SBRT and radical prostatectomy, with QOL assessed at approximately the same times pre- and post-treatment and using the same validated QOL instrument. Patients with clinically localized prostate cancer were treated with either radical prostatectomy (n = 123 Spanish patients) or SBRT (n = 216 American patients). QOL was assessed using the Expanded Prostate Cancer Index Composite (EPIC) grouped into urinary, sexual, and bowel domains. For comparison purposes, SBRT EPIC data at baseline, 3 weeks, 5, 11, 24, and 36 months were compared to surgery data at baseline, 1, 6, 12, 24, and 36 months. Differences in patient characteristics between the two groups were assessed using Chi-squared tests for categorical variables and t-tests for continuous variables. Generalized estimating equation (GEE) models were constructed for each EPIC scale to account for correlation among repeated measures and used to assess the effect of treatment on QOL. The largest differences in QOL occurred in the first 1-6 months after treatment, with larger declines following surgery in urinary and sexual QOL as compared to SBRT, and a larger decline in bowel QOL following SBRT as compared to surgery. Long-term urinary and sexual QOL declines remained clinically significantly lower for surgery patients but not for SBRT patients. Overall, these results may have implications for patient and physician clinical decision making which are often influenced by QOL. These differences in sexual, urinary and bowel QOL should be closely considered in selecting the right treatment, especially in evaluating the value of non-invasive treatments, such as SBRT.


[A clinical analysis on the variance of bone density in patients with cirrhosis].
In 46 patients with decompensated posthepatitis cirrhosis, various clinical manifestations resulted from changes of bone density were noted. The relation between the changes of bone density and the level of blood calcium, blood phosphorus and alkaline phosphatase (AKP) as well as the metabolism of vitamin D was studied. It is shown that: (1) Bone mineral content (BMC) in the cirrhosis group decreased as compared with that in a control group (P < 0.05). (2) Blood calcium and phosphorus level decreased, whereas AKP level increased significantly (P < 0.01) in the cirrhosis group. (3) When BMC decreased, blood calcium and phosphorus level also decreased significantly (P < 0.01). When the condition of cirrhosis deteriorated, these changes became more obvious. The reasons may be: (1) Disorder of vitamin D metabolism in cirrhosis. (2) Decrease of calcium absorption by intestine. (3) Nutritional disturbance. It is suggested that the occurrence of bone rarefaction in cirrhosis was due to multiple factors.


Genetic diversity in Trichomonas vaginalis.
Recent advances in genetic characterisation of Trichomonas vaginalis isolates show that the extensive clinical variability in trichomoniasis and its disease sequelae are matched by significant genetic diversity in the organism itself, suggesting a connection between the genetic identity of isolates and their clinical manifestations. Indeed, a high degree of genetic heterogeneity in T vaginalis isolates has been observed using multiple genotyping techniques. A unique two-type population structure that is both local and global in distribution has been identified, and there is evidence of recombination within each group, although sexual recombination between the groups appears to be constrained. There is conflicting evidence in these studies for correlations between T vaginalis genetic identity and clinical presentation, metronidazole susceptibility, and the presence of T vaginalis virus, underscoring the need for adoption of a common standard for genotyping the parasite. Moving forward, microsatellite genotyping and multilocus sequence typing are the most robust techniques for future investigations of T vaginalis genotype-phenotype associations.


New visions for basic research and primary prevention of pediatric allergy: an iPAC summary and future trends.
Hydrolyzed formula feeding, delayed introduction of solid food, indoor allergen avoidance, smoke and pollutants avoidance have been applied for several decades as primary preventive measures for allergic diseases. Unfortunately, some of these strategies have had no or modest success. Therefore, resources need to be focused on better understanding of the early allergic events and on interventional studies to investigate new strategies of primary and secondary prevention. Accordingly, this review summarizes the state-of-the-art of genetic, immunological and clinical aspects of primary prevention of allergic diseases. Studies investigating gene-by-gene and gene-by-environment interactions suggest that prevention of allergic diseases must be tailored to the individual genetic susceptibilities ('gene profiling') and environmental exposures. The expanding knowledge on new T cell populations (Th17, TSLP (thymic stromal derived lymphopoietin)-dependent 'inflammatory Th2 cells') is also inspiring new concepts on the origins of allergic diseases. The old concept of 'blocking immunoglobulin G antibodies' has been re-appraised and it is likely to generate novel preventive and therapeutic strategies. The major task for future clinical research is to clearly define the timing of optimal exposure to potential allergens. In addition, the role of microbial products such as certain bacteria, or their components, and of helminths or their larvae at different times in early life, alone or with potential allergens, definitely need to be further investigated. The benefit of efficient allergy prevention, based on focusing resources on novel and promising research lines, will be of prime importance to both affluent countries and other parts of the world where allergy is only currently emerging.


Hel-N1/Hel-N2 proteins are bound to poly(A)+ mRNA in granular RNP structures and are implicated in neuronal differentiation.
Human proteins Hel-N1 and Hel-N2 contain three RNA recognition motifs (RRMs), and are members of a family of proteins highly homologous to Drosophila ELAV, which is essential for neuronal differentiation. Both proteins bind to A+U-rich 3' untranslated regions of a variety of growth-related mRNAs in vitro. Here we demonstrate that in medulloblastoma cells derived from childhood brain tumors, Hel-N1 and Hel-N2 are mainly expressed in the cytoplasm, but are detectable in the nucleus. Both proteins are associated with polysomes and can be UV-crosslinked to poly(A)+ mRNA in cell extracts. In the cytoplasm the Hel-N1 protein family resides in granular structures that may contain multiple protein molecules bound to each mRNA. Evidence supporting this multimeric ribonucleoprotein (RNP) model includes in vitro reconstitution and competition experiments in which addition of a single RRM (RRM3) can alter complex formation. As in medulloblastoma cells, the Hel-N1 protein family is present in granular particles in the soma and the proximal regions of dendrites of cultured neurons, and colocalizes with ribosomes. In addition, we demonstrate that expression of the Hel-N1 protein family is up-regulated during neuronal differentiation of embryonic carcinoma P19 cells. Our data suggest that the Hel-N1 protein family is associated with the translational apparatus and implicated in both mRNA metabolism and neuronal differentiation. Furthermore, our findings open the possibility that these proteins participate in mRNA homeostasis in the dendrites and soma of mature neurons.


Bichromatic frequency conversion in potassium niobate.
Two frequency components of an IR laser beam near 980 nm are simultaneously coupled into two adjacent longitudinal modes of a passive ring resonator. A potassium niobate crystal inside the resonator converts the circulating IR light into coherent blue radiation. The total conversion efficiency is enhanced by a factor of 1.4 compared with that of conventional single-mode intracavity second-harmonic generation with the same circulating total power, and we obtain a total output power of 560 mW from 780-mW IR light incident upon the cavity. The spectra of the generated blue radiation and the circulating IR light contain a number of equidistant frequency components that are due to consecutive sum- and difference-frequency mixing.


Improvement of endothelial function early after thrombolytic therapy in patients with prosthetic heart valve thrombosis.
Prosthetic valve thrombosis (PVT) is a serious complication among patients with prosthetic heart valves. Thrombolytic therapy (TT) is now widely used as first-line treatment for PVT. Endothelial dysfunction has previously been reported in patients with PVT. The aim of this study was to investigate the changes in endothelial function soon after TT in PVT patients. The study group included 85 patients with PVT [female: 53 (62.3%); age: 48.7±13.9 years] who were evaluated prospectively before and shortly after TT. All of the patients were evaluated using transthoracic and transesophageal echocardiography. TT was administered in all cases with a low-dose, ultra-slow infusion regimen. Endothelial function was evaluated using a noninvasive measurement of flow-mediated dilatation (FMD) of the brachial artery during reactive hyperemia. The study population included 38 (44.7%) obstructive and 47 (55.3%) non-obstructive PVT patients. The obstructive PVT patients had lower baseline FMD values than the non-obstructive PVT group (5.31±0.76% vs. 5.87±0.84%; p=0.003). TT was successful in 79 patients (92.9%). FMD was significantly increased in the successfully thrombolyzed patients after TT (5.65±0.86% vs. 7.13±1.26%; p<0.001). There was no significant difference in the FMD values after TT in patients who were unresponsive to TT (5.07±0.61% vs. 5.38±0.95%; p=0.371). There was a significant increase in FMD values after TT in patients with obstructive PVT (5.31±0.76% vs. 8.22±1.15%; p<0.001). However, this difference was not statistically significant for patients with non-obstructive PVT (5.87±0.84% vs. 6.11±0.95%; p=0.276). This study demonstrated that successful TT may contribute to improvement of impaired endothelial function in patients with obstructive PVT.


Electrochemical degradation of perfluoroalkyl and polyfluoroalkyl substances (PFASs) in groundwater.
Perfluoroalkyl and polyfluoroalkyl substances (PFASs) represent hazardous pollutants and are frequently detected in the environment, e.g. in contaminated groundwater. PFASs are persistent to biodegradation and conventional oxidation processes such as ozonation. In this study electrochemical degradation of PFASs on boron-doped diamond (BDD) electrodes is demonstrated. Experiments were performed with model solutions and contaminated groundwater with a dissolved organic carbon (DOC) content of 13 mg/L. The perfluorinated carboxylic acids (PFCAs) perfluorobutanoate, perfluoropentanoate, perfluorohexanoate, perfluoroheptanoate and perfluorooctanoate, and the perfluorinated sulfonic acids (PFSAs) perfluorobutane sulfonate, perfluorohexane sulfonate, perfluorooctane sulfonate and 6:2 fluorotelomer sulfonate were detected in the groundwater samples. At PFAS concentrations ranging from 0.26 to 34 mg/L (0.7 to 79 μM), the degradation of PFASs was achieved despite of the high DOC background. Pseudo first-order kinetic constants of PFSA degradation increased with the increase of carbon chain length. Fluoride formation as well as the generation of PFCAs with shortened chain lengths was observed. Inorganic byproducts such as perchlorate were also formed and have to be considered in further process optimization.


A Review of Hot Beverage Temperatures-Satisfying Consumer Preference and Safety.
Hot beverages are served ubiquitously in the food-service industry as well as at residences and other venues. Coffee and tea beverages, in particular, are brewed at temperatures that are sufficiently high to cause immediate and serious risk for scald injuries. On the other hand, numerous research studies have been performed to identify the preferred consumption temperatures for hot beverages. The outcome of these mutually reinforcing studies is that the preferred drinking temperatures are significantly below the often-encountered brewing temperatures (∼200 °F). Consequently, there is great need to distinguish brewing temperatures from serving temperatures. Serving consumers beverages at very high temperatures is not only unnecessary (from a preference standpoint) but also unsafe. An appropriate range for service temperatures is (130 to 160 °F). PRACTICAL APPLICATION: Often times, hot beverages are served at temperatures near their brewing temperature; far hotter than preferred by consumers. This practice creates unnecessary risk to the consumer. A more rationale recommended range of service temperatures is 130 to 160 °F. This recommendation balances a range of consumer preferences and safety.


Smartphone Spectrometers.
Smartphones are playing an increasing role in the sciences, owing to the ubiquitous proliferation of these devices, their relatively low cost, increasing processing power and their suitability for integrated data acquisition and processing in a 'lab in a phone' capacity. There is furthermore the potential to deploy these units as nodes within Internet of Things architectures, enabling massive networked data capture. Hitherto, considerable attention has been focused on imaging applications of these devices. However, within just the last few years, another possibility has emerged: to use smartphones as a means of capturing spectra, mostly by coupling various classes of fore-optics to these units with data capture achieved using the smartphone camera. These highly novel approaches have the potential to become widely adopted across a broad range of scientific e.g., biomedical, chemical and agricultural application areas. In this review, we detail the exciting recent development of smartphone spectrometer hardware, in addition to covering applications to which these units have been deployed, hitherto. The paper also points forward to the potentially highly influential impacts that such units could have on the sciences in the coming decades.


Comparison of information sources for case-referent data.
Exposure assessment and the ascertainment of cases are topics of main concern in epidemiologic research. To investigate validity aspects of this kind practically, a comparative evaluation was performed of information sources for case-referent data. Cases of Hodgkin's disease and non-Hodgkin's lymphoma diagnosed in 1975-1984 were collected from the Regional Cancer Register in Linköping. The study population was restricted to men 20-80 years of age at diagnosis. Living cases included in a previous case-referent study and the complementary cases from the register were compared with regard to the exposures indicated by job title and industrial branch, as given in the National Population Census in 1975. Furthermore, questionnaire-based exposure information from the case-referent study was compared with exposures derived from census information. Only 21% of all of the cases in the study base had been included in the questionnaire-based case-referent study. No major differences in the distribution of exposure were found for the two case series, except that fewer subjects were economically inactive in the previous case-referent study. No clear relations appeared between survival and particular exposures. Risk estimates derived from the present cancer register study were compared with corresponding estimates from the previous case-referent study. With restriction to only economically active cases, the risk estimates approached those of the case-referent study. This comparison showed that incomplete ascertainment of cases in a case-referent study was not an important source of bias, at least not in relation to what could be achieved by more complete case ascertainment through register linkage.


Tailored TiO2-SrTiO3 heterostructure nanotube arrays for improved photoelectrochemical performance.
TiO(2) nanotube arrays formed on Ti substrate by electrochemical anodization have been converted into TiO(2)-SrTiO(3) heterostructures by controlled substitution of Sr under hydrothermal conditions. The growth of SrTiO(3) crystallites on the nanotube array electrode was probed by electron microscopy and X-ray diffraction. As the degree of Sr substitution increases with the duration of hydrothermal treatment, an increase in the size of SrTiO(3) crystallites was observed. Consequently, with increasing SrTiO(3) fraction in the TiO(2)-SrTiO(3) nanotube arrays, we observed a shift in the flat band potential to more negative potentials, thus confirming the influence of SrTiO(3) in the modification of the photoelectrochemical properties. The TiO(2)-SrTiO(3) composite heterostructures obtained with 1 h or less hydrothermal treatment exhibit the best photoelectrochemical performance with nearly 100% increase in external quantum efficiency at 360 nm. The results presented here provide a convenient way to tailor the photoelectrochemical properties of TiO(2)-SrTiO(3) nanotube array electrodes and employ them for dye- or quantum-dot-sensitized solar cells and/or photocatalytic hydrogen production.


Pharmacology and functions of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide: IUPHAR review 1.
Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are members of a superfamily of structurally related peptide hormones that includes glucagon, glucagon-like peptides, secretin, gastric inhibitory peptide (GIP) and growth hormone-releasing hormone (GHRH). VIP and PACAP exert their actions through three GPCRs - PAC(1) , VPAC(1) and VPAC(2) - belonging to class B (also referred to as class II, or secretin receptor-like GPCRs). This family comprises receptors for all peptides structurally related to VIP and PACAP, and also receptors for parathyroid hormone, corticotropin-releasing factor, calcitonin and related peptides. PAC(1) receptors are selective for PACAP, whereas VPAC(1) and VPAC(2) respond to both VIP and PACAP with high affinity. VIP and PACAP play diverse and important roles in the CNS, with functions in the control of circadian rhythms, learning and memory, anxiety and responses to stress and brain injury. Recent genetic studies also implicate the VPAC(2) receptor in susceptibility to schizophrenia and the PAC(1) receptor in post-traumatic stress disorder. In the periphery, VIP and PACAP play important roles in the control of immunity and inflammation, the control of pancreatic insulin secretion, the release of catecholamines from the adrenal medulla and as co-transmitters in autonomic and sensory neurons. This article, written by members of the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR) subcommittee on receptors for VIP and PACAP, confirms the existing nomenclature for these receptors and reviews our current understanding of their structure, pharmacology and functions and their likely physiological roles in health and disease. More detailed information has been incorporated into newly revised pages in the IUPHAR database (http://www.iuphar-db.org/DATABASE/FamilyMenuForward?familyId=67).


Maximum likelihood methods in biology revisited with tools of computational intelligence.
We investigate the problem of identification of genes correlated with the occurrence of diseases in a given population. The classical method of parametric linkage analysis is combined with newer tools and results are achieved on a model problem. This traditional method has advantages over non-parametric methods, but these advantages have been difficult to realize due to their high computational cost. We study a class of Evolutionary Algorithms from the Computational Intelligence literature which are designed to cut such costs considerably for optimization problems. We outline the details of this algorithm, called Particle Swarm Optimization, and present all the equations and parameter values we used to accomplish our optimization. We view this study as a launching point for a wider investigation into the leveraging of computational intelligence tools in the study of complex biological systems.


A quantitative look at fluorosis, fluoride exposure, and intake in children using a health risk assessment approach.
The prevalence of dental fluorosis in the United States has increased during the last 30 years. In this study, we used a mathematical model commonly employed by the U.S. Environmental Protection Agency to estimate average daily intake of fluoride via all applicable exposure pathways contributing to fluorosis risk for infants and children living in hypothetical fluoridated and nonfluoridated communities. We also estimated hazard quotients for each exposure pathway and hazard indices for exposure conditions representative of central tendency exposure (CTE) and reasonable maximum exposure (RME) conditions. The exposure pathways considered were uptake of fluoride via fluoridated drinking water, beverages, cow's milk, foods, and fluoride supplements for both age groups. Additionally, consumption of infant formula for infants and inadvertent swallowing of toothpaste while brushing and incidental ingestion of soil for children were also considered. The cumulative daily fluoride intake in fluoridated areas was estimated as 0.20 and 0.11 mg/kg-day for RME and CTE scenarios, respectively, for infants. On the other hand, the RME and CTE estimates for children were 0.23 and 0.06 mg/kg-day, respectively. In areas where municipal water is not fluoridated, our RME and CTE estimates for cumulative daily average intake were, respectively, 0.11 and 0.08 mg/kg-day for infants and 0.21 and 0.06 mg/kg-day for children. Our theoretical estimates are in good agreement with measurement-based estimates reported in the literature. Although CTE estimates were within the optimum range for dental caries prevention, the RME estimates were above the upper tolerable intake limit. This suggests that some children may be at risk for fluorosis.


Nanoparticle delivery of curcumin induces cellular hypoxia and ROS-mediated apoptosis via modulation of Bcl-2/Bax in human neuroblastoma.
In this study, several formulations of nanoceria and dextran-nanoceria with curcumin, each demonstrated to have anti-cancer properties, were synthesized and applied as treatment for human childhood neuroblastoma. The anti-cancer activities of these formulations were explored in neuroblastoma models of both MYCN-amplified and non-amplified cell lines. Ceria nanoparticles, coated with dextran and loaded with curcumin, were found to induce substantial cell death in neuroblastoma cells (up to a 2-fold and a 1.6-fold decrease in cell viability for MYCN-upregulated and normal expressing cell lines, respectively; *p < 0.05) while producing no or only minor toxicity in healthy cells (no toxicity at 100 μM; **p < 0.01). This formulation evokes prolonged oxidative stress, stabilizing HIF-1α, and inducing caspase-dependent apoptosis (up to a 2.4-fold increase over control; *p < 0.05). Overall, nano-therapeutic treatments showed a more pronounced effect in MYCN-amplified cells, which are traditionally more resistant to drug therapies. These results represent a very promising alternative to small molecule drug therapies for robust cancers.


Low prevalence of Borna disease virus 1 (BoDV-1) IgG antibodies in humans from areas endemic for animal Borna disease of Southern Germany.
Borna disease virus-1 (BoDV-1) was recently discovered as cause of severe and often fatal encephalitis in humans. BoDV-1 is known to cause neurological disease in horses and sheep mainly in South and Central Germany. The virus is maintained in bicolored white-toothed shrews (Crocidura leucodon). The incidence of infection and risk factors in humans are completely unresolved. Veterinarians may be disproportionally BoDV-1-exposed through contact to animals not recognized to be BoDV-1 infected. We conducted three serosurveys predominantly in endemic areas of South Germany for the presence of BoDV-1-reactive antibodies. Anonymized residual samples from two serosurveys of veterinarians (n = 736) with interview data on exposures and one serosurvey among blood donors (n = 373) were screened with an indirect immunofluorescence antibody test, followed by a newly developed immunoblot as confirmatory assay. One serum from a 55-59-year-old veterinarian who worked in an animal practice and as a meat inspector but none from blood donors tested positive by the screening and confirmatory assays. We show that seropositive individuals are rare even in areas with highest zoonotic risk and in a group with potentially elevated exposure risk. In light of the low seroprevalence demonstrated here, the high case-fatality rate in clinically observed human BoDV-1 infections is even more impressive.


Effect of a change in gender on coronary arterial size: a longitudinal intravascular ultrasound study in transplanted hearts.
We sought to document whether a physiologic change in gender has any effect on coronary arterial size. The coronary arteries are smaller in women, even after correction for body surface area (BSA). These differences may contribute to adverse clinical outcomes after coronary artery bypass graft surgery and myocardial infarction in women. In male and female transsexuals, pharmacologic doses of estrogens and androgens significantly influence vascular diameter. Thus, gender differences in the coronary vasculature may be a reflection of the hormonal environment. In 86 patients who had undergone orthotopic heart transplantation, serial intravascular ultrasound studies of the proximal left anterior descending coronary artery (LAD) were analyzed. Changes in vessel area (VA) over the first or second post-transplant year were recorded, and comparisons were made between donor hearts that were transplanted in a patient of the same gender and those that were transplanted in a patient of the opposite gender. Vessel area of the proximal LAD increased over time in all patient groups. In hearts transplanted within the same gender and in male donor hearts transplanted to female recipients, the change was small and not significant. However, in hearts transplanted from female donors to male recipients, there was a substantial and highly significant increase in LAD VA (median 16.13 to 17.88 mm(2); p = 0.01). This increase was not explained by confounding due to changes in BSA or left ventricular wall thickness. This pattern of arterial remodeling early after heart transplantation supports a link between host gender and coronary arterial size.


Aerating grasslands: effects on runoff and phosphorus losses from applied broiler litter.
Aeration has been promoted as improving infiltration of rainfall and extending grass or forage productivity, but research on the impact of this practice on P losses from grasslands has had mixed results. We designed a study to determine at the field scale, using a paired watershed approach, the impact of slit aeration on runoff volume and P losses in runoff from fescue (Festuca arundinacea Schreb.)/bermudagrass (Cynodon dactylon L.) hay fields fertilized with broiler litter. Three pairs of 0.8-ha fields, each with similar soils (Typic Kanhapludults, Aquic Hapludults, and Aquultic Hapludalfs), were fertilized with broiler litter and monitored under similar management from 1995 through 1998, then one field in each pair received aeration treatment from 2001 through 2003. In the field with mostly well-drained soils, grassland aeration reduced surface runoff volume and mass losses of dissolved reactive P (DRP) in runoff by approximately 35%. In contrast, when poorly drained soils dominated, grassland aeration increased runoff volume (4.8 mm/runoff event) and mass losses of DRP and total P (0.25 kg TP ha-1 per runoff event). This implies that aeration of well-drained soils in the top poultry-producing counties of Georgia (0.2 million ha) could decrease dissolved phosphorus losses by more than 500 Mg P each year. This is not the case if soils are poorly drained.


Characterization of static and dynamic left ventricular diastolic function in patients with heart failure with a preserved ejection fraction.
Congestive heart failure in the setting of a preserved left ventricular (LV) ejection fraction is increasing in prevalence among the senior population. The underlying pathophysiologic abnormalities in ventricular function and structure remain unclear for this disorder. We hypothesized that patients with heart failure with preserved ejection fraction (HFPEF) would have marked abnormalities in LV diastolic function with increased static diastolic stiffness and slowed myocardial relaxation compared with age-matched healthy controls. Eleven highly screened patients (4 men, 7 women) aged 73±7 years with HFPEF were recruited to participate in this study. Thirteen sedentary healthy controls (7 men, 6 women) aged 70±4 years also were recruited. All subjects underwent pulmonary artery catheterization with measurement of cardiac output, end-diastolic volumes, and pulmonary capillary wedge pressures at baseline; cardiac unloading (lower-body negative pressure or upright tilt); and cardiac loading (rapid saline infusion). The data were used to define the Frank-Starling and LV end-diastolic pressure-volume relationships. Doppler echocardiographic data (tissue Doppler velocities, isovolumic relaxation time, propagation velocity of early mitral inflow , E/A-wave ratio) were obtained at each level of cardiac preload. Compared with healthy controls, patients with HFPEF had similar LV contractile function and static LV compliance but reduced LV chamber distensibility with elevated filling pressures and slower myocardial relaxation as assessed by tissue Doppler imaging. In this small, highly screened patient population with hemodynamically confirmed HFPEF, increased end-diastolic static ventricular stiffness relative to age-matched controls was not a universal finding. Nevertheless, patients with HFPEF, even when well compensated, had elevated filling pressures, reduced distensibility, and increased diastolic wall stress compared with controls. In contrast, LV relaxation as assessed by tissue Doppler variables appeared consistently impaired in patients with HFPEF.


New non-invasive biomarkers for colorectal cancer screening.
Colorectal cancer (CRC) is one of the most frequent neoplasia in developed countries and the second leading cause of cancer death in Spain. It develops through the accumulation of genetic and epigenetic alterations in the normal mucosa, producing advanced adenomas and invasive cancers. This multistep process makes CRC highly traceable, making it a good candidate for the implementation of preventive measures such as screening programs. Although there are different strategies, none of them meet all the criteria for CRC screening purposes. In this context, many molecular alterations involved in CRC carcinogenesis could contribute to the generation of new non-invasive methods with a high sensitivity and specificity. In this review, some of the most promising diagnostic non-invasive biomarkers for CRC will be briefly discussed.


Phylogeny of the genus Synchytrium and the development of TaqMan PCR assay for sensitive detection of Synchytrium endobioticum in soil.
Potato wart, caused by the fungal pathogen Synchytrium endobioticum, is a serious disease with the potential to cause significant economic damage. The small subunit (SSU) and internal transcribed spacer (ITS) ribosomal DNA (rDNA) were sequenced for several Synchytrium spp., showing a high rate of variability for both of these markers among the different species and monophyly of the genus within phylum Chytridiomycota. The intergenic nontranscribed spacer (IGS) of rDNA was sequenced for different pathotypes and showed no intraspecific variation within S. endobioticum, similar to the other rDNA markers from this study. To facilitate screening for the pathogen in soil, three TaqMan polymerase chain reaction (PCR) assays were developed from SSU, ITS, and IGS rDNA sequences to detect S. endobioticum sporangia in the chloroform-flotation fraction of sieved soil extracts. In the screening portion of the method, a first TaqMan assay targeting the SSU rDNA was developed with positive results that were further confirmed with amplicon melt analysis. A synthetic reaction control cloned into a plasmid was incorporated into the procedure, facilitating the validation of negative results. The presence of the reaction control did not adversely affect the efficiency of the SSU target amplification. A second TaqMan assay targeting the ITS-1 region was developed as a confirmatory test. There was 100% accordance between the SSU and ITS-1 TaqMan assays. Utilizing these two assays in tandem achieved good specificity for S. endobioticum, generating negative results with the cloned SSU and ITS-1 regions from all 14 other Synchytrium spp. considered. Spike recovery experiments indicated that these assays, targeting the SSU and ITS-1 rDNA regions, developed from a phylogeny dataset of the genus, could reliably detect a single sporangium in the chloroform flotation fraction of a soil extract. Good correlation between microscopic detection of sporangia and PCR results in both positive and negative soil samples was dually demonstrated for both the SSU and ITS-1 assays.


Nontwist quarter-wave liquid-crystal cell for a high-contrast reflective display.
We propose an optical configuration of a nontwist quarter-wave liquid-crystal cell for a high-contrast reflective display that can be applied to most nontwist display modes. By fabricating a homogeneous cell with the proposed configuration, we have demonstrated a high contrast ratio of 50:1 without using a wideband retardation film.


Cellular manganese content is developmentally regulated in human dopaminergic neurons.
Manganese (Mn) is both an essential biological cofactor and neurotoxicant. Disruption of Mn biology in the basal ganglia has been implicated in the pathogenesis of neurodegenerative disorders, such as parkinsonism and Huntington's disease. Handling of other essential metals (e.g. iron and zinc) occurs via complex intracellular signaling networks that link metal detection and transport systems. However, beyond several non-selective transporters, little is known about the intracellular processes regulating neuronal Mn homeostasis. We hypothesized that small molecules that modulate intracellular Mn could provide insight into cell-level Mn regulatory mechanisms. We performed a high throughput screen of 40,167 small molecules for modifiers of cellular Mn content in a mouse striatal neuron cell line. Following stringent validation assays and chemical informatics, we obtained a chemical 'toolbox' of 41 small molecules with diverse structure-activity relationships that can alter intracellular Mn levels under biologically relevant Mn exposures. We utilized this toolbox to test for differential regulation of Mn handling in human floor-plate lineage dopaminergic neurons, a lineage especially vulnerable to environmental Mn exposure. We report differential Mn accumulation between developmental stages and stage-specific differences in the Mn-altering activity of individual small molecules. This work demonstrates cell-level regulation of Mn content across neuronal differentiation.


A two-compartment model of synaptic computation and plasticity.
The synapse is typically viewed as a single compartment, which acts as a linear gain controller on incoming input. Traditional plasticity rules enable this gain control to be dynamically optimized by Hebbian activity. Whilst this view nicely captures postsynaptic function, it neglects the non-linear dynamics of presynaptic function. Here we present a two-compartment model of the synapse in which the presynaptic terminal first acts to filter presynaptic input before the postsynaptic terminal, acting as a gain controller, amplifies or depresses transmission. We argue that both compartments are equipped with distinct plasticity rules to enable them to optimally adapt synaptic transmission to the statistics of pre- and postsynaptic activity. Specifically, we focus on how presynaptic plasticity enables presynaptic filtering to be optimally tuned to only transmit information relevant for postsynaptic firing. We end by discussing the advantages of having a presynaptic filter and propose future work to explore presynaptic function and plasticity in vivo.


Grammatical gender and number agreement in Spanish: an ERP comparison.
The role of grammatical gender and number representations in syntactic processes during reading in Spanish was studied using the event-related potentials (ERPs) technique. The electroencephalogram was recorded with a dense array of 128 electrodes while Spanish speakers read word pairs (Experiment 1) or sentences (Experiment 2) in which gender or number agreement relationships were manipulated. Disagreement in word pairs formed by a noun and an adjective (e.g., faro-alto [lighthouse-high]) produced an N400-type effect, while word pairs formed by an article and a noun (e.g., el-piano [the-piano]) showed an additional left anterior negativity effect (LAN). Agreement violations with the same words inserted in sentences (e.g., El piano estaba viejo y desafinado [the (m-s)piano (m-s) was old (m-s) and off-key]) resulted in a pattern of LAN-P600. This effect was found both when the violation occurred in the middle of the sentence (at the adjective), as well as when this happened at the beginning of the sentence (at the noun), but the last segment of the P600 effect was greater for the middle sentence position, which could indicate differences in the complexity of reanalysis processes. Differences between grammatical gender and number disagreement were found in late measures. In the word pairs experiment, P3 peak latency varied across conditions, being later for gender than for number disagreement. Similarly, in the sentence experiment, the last segment of the P600 effect was greater for gender than for number violations. These event-related potentials (ERPs) effects lend support to the idea that reanalysis or repair processes after grammatical disagreement detection could involve more steps in the case of gender disagreement, as grammatical gender is a feature of the lexical representation in contrast to number, which is considered a morphological feature that combines with the stem of the word.


New insights into DNA-binding behavior of Wilms tumor protein (WT1)--a dual study.
Wilms Tumor suppressor protein (WT1) is a transcription factor that is involved in a variety of developmental functions during organ development. It is also implicated in the pathology of several different cancer forms. The protein contains four C(2)H(2)-type zinc fingers and it specifically binds GC-rich sequences in the promoter regions of its target genes, which are either up or down regulated. Two properties make WT1 a more unusual transcription factor - an unconventional amino acid composition for zinc finger 1, and the insertion of a tri-peptide KTS in some of the splice isoforms of WT1. Using six WT1 constructs in which zinc fingers are systematically deleted, a dual study based on a bacterial 1-hybrid system and surface plasmon resonance measurements is performed. The experiments show that the effect of zinc finger 1 is not significant in terms of overall DNA-binding kinetics, however it influences both the specificity of target recognition and stability of interaction in presence of KTS. The KTS insertion, however, only mildly retards binding affinity, mainly by affecting the on-rate. We suggest that the insertion disturbs zinc finger 4 from its binding frame, thus weakening the rate of target recognition. Finally, for the construct in which both zinc fingers 1 and 4 were deleted, the two middle fingers 2-3 still could function as a 'minimal DNA-recognition domain' for WT1, however the formation of a stable protein-DNA complex is impaired since the overall affinity was dramatically reduced mainly since the off-rate was severely affected.


Non-pharmacological interventions for agitation in dementia: systematic review of randomised controlled trials.
Agitation in dementia is common, persistent and distressing and can lead to care breakdown. Medication is often ineffective and harmful. To systematically review randomised controlled trial evidence regarding non-pharmacological interventions. Method We reviewed 33 studies fitting predetermined criteria, assessed their validity and calculated standardised effect sizes (SES). Person-centred care, communication skills training and adapted dementia care mapping decreased symptomatic and severe agitation in care homes immediately (SES range 0.3-1.8) and for up to 6 months afterwards (SES range 0.2-2.2). Activities and music therapy by protocol (SES range 0.5-0.6) decreased overall agitation and sensory intervention decreased clinically significant agitation immediately. Aromatherapy and light therapy did not demonstrate efficacy. There are evidence-based strategies for care homes. Future interventions should focus on consistent and long-term implementation through staff training. Further research is needed for people living in their own homes.


Axial lumbosacral interbody fusion appears safe as a method to obtain lumbosacral arthrodesis distal to long fusion constructs.
Current methods to achieve lumbosacral interbody fusion have been complicated by approach-related morbidity, nerve root or cauda equina injury, or difficulty in implanting a large lordotic graft posteriorly. There is little information in the literature evaluating the presacral axial approach to the lumbosacral disc space. What are the short-term clinical and radiographic outcomes in patients undergoing axial lumbosacral interbody fixation and fusion at the end of long fusion constructs using the AxiaLIF implant (Trans1 Inc., Wilmington, NC, USA)? Furthermore, what complications are associated with this procedure? We performed a retrospective evaluation of nine patients who underwent presacral axial lumbosacral interbody fixation and fusion at the end of long fusion constructs using the AxiaLIF implant. Preoperative diagnoses included adjacent segment degeneration below a long fusion construct for adult scoliosis and progressive sagittal plane deformity. There were two pseudoarthroses, one at L4-5 and one at L5-S1. No major complications occurred. There were no significant differences in coronal or sagittal plane alignment at the time periods measured. There was no significant difference in implant position between immediate postoperative and final follow-up periods. There were significant postoperative improvements in Scoliosis Research Society-22 scores, specifically in the pain, self-image, and satisfaction with management domains. The axial lumbosacral interbody fusion is a minimally invasive and safe method to obtain lumbosacral fixation and arthrodesis distal to a long fusion construct. Longer follow-up of larger numbers of patients are needed prior to recommending this procedure as a routine method to fuse L4-5 or L5-S1.


Immunological cross-reactivity between human tripeptidyl peptidase II and fibronectin.
Tripeptidyl peptidase II (TPP II) is a large intracellular exopeptidase with an active site of the subtilisin type. Affinity-purified hen antibodies against human erythrocyte TPP II cross-reacted with fibronectin in an immunoblot analysis. Furthermore, antibodies against human fibronectin cross-reacted with TPP II. Antibodies against a 65 kDa cell-binding fragment of fibronectin specifically reacted with TPP II, whereas antibodies against the collagen-binding domain, the main heparin-binding domain or the N-terminal fibrin-binding domain did not react. Moreover, the affinity-purified antibodies against TPP II reacted with a 105 kDa cell-binding fragment of fibronectin but not with the fibrin-binding domain or the collagen-binding domain. When native TPP II was dissociated into smaller units through dialysis against a dilute Tris buffer, it could be digested by chymotrypsin into three stable fragments of 70 kDa, 42 kDa and 20 kDa. It could be demonstrated that the 42 kDa fragment was specifically recognized by antibodies against the 65 kDa cell-binding fragment of fibronectin. Furthermore, labelling with di-[3H]isopropyl phosphorofluoridate and N-terminal sequence determination showed that the 70 kDa fragment contained the active-site serine residue. In conclusion, our findings suggest that one domain of the TPP II molecule bears structural resemblance to a cell-binding fragment of fibronectin.


Delivery of nipple-sparing mastectomy within a single healthcare system: The impact of provider preferences.
Nipple-sparing mastectomy (NSM) offers superior esthetic outcomes without sacrificing oncologic safety for select patients requiring mastectomy. While disparities in oncologic care are well established, no study to date has investigated equitable delivery of the various mastectomy types. The objective of this study is to examine multilevel factors related to the distribution of NSM. Patients undergoing mastectomy between 2014 and 2018 across eight hospitals in a single healthcare system were retrospectively reviewed. Patients were categorized by mastectomy type-NSM or other mastectomy (OM). Patient information such as age, race, comorbidities, and median income by ZIP code was collected. Disease characteristics, such as mastectomy weight, breast cancer stage, and treatment history, were identified. Provider and system-level variables, such as specific provider, hospital of operation, and insurance status, were determined. Bivariate analysis was used to identify variables for inclusion in a backward multivariable model. A cohort of 1202 mastectomy patients was identified, with 388 receiving NSM. The average age was 55.8 years (NSM: 48.8, OM: 59.1, P < .001). 39.8% of white patients (n = 242) and 20.0% of African American patients (n = 88) received NSM (P < .001). Average mastectomy weight was 384.3 (SD 195.7) in the NSM group, compared to 839.4 (SD 521.1) in the OM group (P < .001). 41.4% (n = 359) of patients treated at academic centers, and 6.9% (n = 21) of patients treated at community centers received NSM (P < .001). In the multivariate model, the factor with the largest impact on NSM was specific provider. Odds of NSM decreased by 76%-88% for certain surgeons, while odds increased by 63 times for one surgeon. This study utilizes a large multi-institutional database to highlight disparities in NSM delivery. Expectedly, younger, relatively healthy patients, with smaller breast size were more likely to undergo NSM, in accordance with surgical guidelines. However, when all other factors were controlled, provider preferences played the most significant role in NSM delivery rates. These findings demonstrate the need for practice reexamination to ensure equitable access to NSM.


Cysticercosis control: bringing advances to the field.
Progress towards Taenia solium control is evident in the development of new technologies and in increasing regional coordination, yet disease eradication remains unlikely in the near future. In the meantime, translation of research advances into functioning control programs is necessary to address the ongoing disease burden in endemic areas. Multiple screening assays, effective treatments for both human and porcine infection, and vaccines blocking transmission to pigs are currently available. Strategies based on identification and treatment of T. solium adult tapeworms, as well as interventions that block cysticercosis acquisition in pigs have temporarily reduced transmission. Building on these successes with controlled community trials in varying endemic scenarios will drive progress towards regional elimination.