Development of a personalized decision aid for breast cancer risk reduction and management.
Breast cancer risk reduction has the potential to decrease the incidence of the disease, yet remains underused. We report on the development a web-based tool that provides automated risk assessment and personalized decision support designed for collaborative use between patients and clinicians. Under Institutional Review Board approval, we evaluated the decision tool through a patient focus group, usability testing, and provider interviews (including breast specialists, primary care physicians, genetic counselors). This included demonstrations and data collection at two scientific conferences (2009 International Shared Decision Making Conference, 2009 San Antonio Breast Cancer Symposium). Overall, the evaluations were favorable. The patient focus group evaluations and usability testing (N = 34) provided qualitative feedback about format and design; 88% of these participants found the tool useful and 94% found it easy to use. 91% of the providers (N = 23) indicated that they would use the tool in their clinical setting. BreastHealthDecisions.org represents a new approach to breast cancer prevention care and a framework for high quality preventive healthcare. The ability to integrate risk assessment and decision support in real time will allow for informed, value-driven, and patient-centered breast cancer prevention decisions. The tool is being further evaluated in the clinical setting.


Bilski: assessing the impact of a newly invigorated patent-eligibility doctrine on the pharmaceutical industry and the future of personalized medicine.
The patent-eligibility doctrine serves a gatekeeper role in excluding from patent protection natural phenomena, principles of nature, abstract ideas, and mental processes. Beginning around 1980, the U.S. patent system embarked upon a pronounced expansion in its definition of patent-eligible subject matter, particularly with respect to software and business method inventions, but also in the life sciences. In recent years, however, we have seen a backlash, with many critics from the public and private sectors arguing that the threshold for patent-eligibility needs to be raised in order to ensure that patents fulfill their constitutional objective of encouraging innovation rather than impeding it. The courts and PTO appear to have heard these critics, and have begun to actively rein in the scope of patent-eligible subject matter. This shift in the swing of the patent-eligibility pendulum will likely have a profound impact on the patentability of innovations arising out of the pharmaceutical and biotechnology industries, particularly those relating to diagnostics and personalized medicine. In this article, I discuss the current status of the patent-eligibility doctrine, how it is that we got here, and what the future might hold, particularly for the life science industries.


Perioperative management issues of direct oral anticoagulants.
The treatment repertoire of oral anticoagulation has changed dramatically over the past few years from one class of vitamin K1 antagonists to an increasing number of direct oral anticoagulants (DOACs). Clinicians are confronted with the problem of managing patients on novel agents in the critical setting before, during, and after surgery, where the risk of bleeding and thrombosis are increased simultaneously. Randomized clinical data are insufficient to date, but clinical exposure enlarges the body of experience. The following review considers perioperative management issues in various categories, including minor elective surgery, major elective surgery, and acute surgery. This review is a credo to personalized medicine where the patient's underlying thromboembolic risk status, the potential bleeding risk, or actual hemorrhagic manifestation determine the selection of multi-modal targeted management strategies.


Reduced inequality in access to stroke unit care over time: a 15-year follow-up of socioeconomic disparities in Sweden.
Despite the compelling scientific evidence on the superiority of stroke unit care, far from all acute stroke patients have access to stroke unit care. In congruence with what has been observed when other new methods are introduced in health care, we hypothesized that there has been an inequality in the buildup phase of stroke units but that the gradients between patient groups have decreased as the total capacity of stroke unit care has increased. The purpose of this study was to explore if patients in a national sample who were socioeconomically disadvantaged (low education or low income) had reduced access to stroke unit care and if differences varied over time. All patients 18-74 years of age registered between 1995 and 2009 in Riks-Stroke, the Swedish stroke register, were included. The Stroke Unit Trialists' definition of a stroke unit has been adopted by Riks-Stroke and hospitals participating in the registry. Basic patient characteristics, stroke risk factors, process and outcome variables are recorded in Riks-Stroke. Socioeconomic data were accessed from Statistics Sweden. Multiple logistic regression analyses were used to calculate odds ratios (ORs) for stroke unit care between prespecified patient subgroups. A total of 319,240 stroke patients were included in Riks-Stroke during the years 1995-2009, and 124,173 were aged between 18 and 74 years; they were included in the final analyses. After adjustment for confounders in a multiple regression model, women were treated in stroke units slightly less often [OR 0.97, 95% confidence interval (CI) 0.95-0.99]. There were no statistically significant associations between stroke unit care and age or between stroke unit care and cohabiting or living alone. The highest level of education predicted access to stroke unit care (secondary vs. primary school: OR 1.04, 95% CI 1.01-1.07; university vs. primary school: OR 1.06, 95% CI 1.02-1.10). Differences according to level of education diminished over time (p = 0.001). Income was not independently associated with stroke unit care, and over time the proportion of patients treated in stroke units increased at a similar rate in all income groups (p = 0.12). Even in a country with modest socioeconomic differences in the general population and public financing of all acute hospital care, socioeconomic inequalities in access to stroke unit care were evident during the early years, but they diminished as the total capacity for stroke unit care increased.


The experiences and perceptions of mental health service provision at a primary health centre in the Eastern Cape.
Since 1994, the South African healthcare system has undergone several changes to meet the needs of contemporary South Africa. Yet the state of mental healthcare, especially in low-resource areas, remains in a precarious state. This study aimed to explore how persons diagnosed with a mental disorder experience and perceive mental health services in a low-resource community in the Eastern Cape, South Africa. The study was conducted at a primary care clinic in a low resource community setting in the Eastern Cape, South Africa. Semi-structured interviews were conducted with eight participants diagnosed with mental illness who had been accessing treatment for at least the past 6 months from a primary health clinic. Thematic analysis was used to analyse and identify pertinent themes. The following themes emerged from the data: (1) perceptions of mental disorders - role of culture, (2) experiences of having mental disorders - loss of employment, (3) problem of stigma - social rejection and labelling, (4) experience of distress - sadness and frustration and (5) challenges in accessing treatment - transport fee and shortage of staff. This study yielded several lived experiences and perceptions in relation to participants' feelings, opinions and interpretations of persons living with mental disorders and accessing mental health treatment in their local context. Future interventions should consider provision of more extensive professional help in the form of counsellors and social workers at the clinics, more efficient service delivery and future interventions regarding stigma should incorporate community members into the learning process.


Aggregatibacter actinomycetemcomitans Cytolethal Distending Toxin-Induces Cell Cycle Arrest in a Glycogen Synthase Kinase (GSK)-3-Dependent Manner in Oral Keratinocytes.
Cytolethal distending toxins (Cdt) are produced by a diverse group of pathogens. One Cdt-producing organism, Aggregatibacter actinomycetemcomitans, plays a critical role in the pathogenesis of a unique form of periodontitis, formerly referred to as localized aggressive periodontitis. The active Cdt subunit, CdtB, is a potent phosphatidylinositol (PI) 3,4,5-triphosphate phosphatase capable of inducing PI-3-kinase signaling blockade, a requisite for Cdt-induced toxicity in lymphocytes. In this study, we extended our observations to include the oral keratinocyte response to AaCdt using cell lines and primary gingival keratinocytes. All three exhibited G2/M arrest when exposed to AaCdt toxin within 24 h. Toxin-treated cells exhibited reduced levels of pAkt and pGSK3β within 6 h. Pre-treatment with GSK3β kinase inhibitors, LY2090314, CHIR99021 and Tideglusib, abrogated Cdt-induced G2/M arrest. None of the oral epithelial cells exhibited evidence of apoptosis. Cells remained arrested in the G2/M phase for at least 72 h without evidence of DNA damage response activation (H2AX phosphorylation). Cdt-treated cells displayed increased phosphorylation of the cyclin dependent kinase 1 (CDK1); moreover, the GSK3 inhibitors blocked this increase and reduced total CDK1 levels. This study further clarifies the potential mechanism(s) contributing to Cdt toxicity and toxin-mediated pathogenesis.


Changes in skeletal-muscle myosin isoenzymes with hypertrophy and exercise.
The patterns of myosin isoenzymes in fast- and slow-twitch muscles of the rat hindlimb were studied, by pyrophosphate/polyacrylamide-gel electrophoresis, with hypertrophy (induced by synergist removal) and with spontaneous running exercise of 4 and 11 weeks duration. At 11 weeks, changes with hypertrophy in the slow-twitch soleus, composed of greater than 95% SM2 (slow myosin 2) in normal muscles, were minor, and consisted of an increase in the SM1 and SM1', and a loss of intermediate myosin (IM), an isoenzyme characteristic of Type IIa fibres [Fitzsimons & Hoh (1983) J. Physiol. (London) 343, 539-550]. The changes were dramatic, however, in the fast-twitch plantaris muscle. There was a 3-fold increase in the proportion of SM. In addition, IM became the predominant isoenzyme in the profile of hypertrophied plantaris by 4 weeks. These increases were balanced by decreases in the proportion of FM2 (fast myosin 2), with FM1 completely absent from the profile at 11 weeks. The changes in the plantaris with exercise were similar in direction but not as extensive as those with hypertrophy, and FM1 remained present at control levels throughout the study. When hypertrophy and exercise were combined, the increase in slow myosin was equal to the sum of the increases with each treatment alone. Changes at 4 weeks were intermediate between those of control and 11-week muscles. Peptide mapping of individual myosin isoenzymes showed that the heavy chains of IM were different from either fast or slow heavy chains. Furthermore, IM was found to be composed of a mixture of fast and slow light chains. These changes suggest that a transformation of myosin from fast to slow isoforms was in progress in the plantaris in response to hypertrophy, via a Type-IIa-myosin (IM) intermediate stage, a phenomenon similar to that occurring in chronically stimulated fast muscles during fast-to-slow transformation [Brown, Salmons & Whalen (1983) J. Biol. Chem. 258, 14686-14692].


A non-planar 2D covalent organic framework derived from a Z-shaped building unit.
Herein, a novel non-planar 2D COF with a stair-stepped structure was constructed from a Z-shaped building block for the first time. Compared with its similar planar COF, the unique stair-stepped non-planar COF possesses larger surface area and stronger fluorescence, which was further applied for specific explosive detection through a fluorescence quenching mechanism. This work not only extends the traditional planar 2D COF structures to unique non-planar structures based on the bottom-up design principle, but also expands the potential applications of COF materials.


A multifactorial postoperative surveillance model for patients with surgically treated clear cell renal cell carcinoma.
We designed scoring algorithms for postoperative surveillance based on multivariately significant predictors of site specific disease recurrence. We identified 1,864 patients who underwent partial or radical nephrectomy for nonmetastatic clear cell renal cell carcinoma between 1970 and 2000. Clinical features studied included age, sex and symptomatic disease at presentation. Surgical and pathological features studied included nephrectomy type, surgical margin status, 2003 TNM stage, nuclear grade, histological tumor necrosis, sarcomatoid component, cystic architecture and multifocality. Recurrence was classified into locations of abdomen, thoracic region, bone and brain. Recurrence-free survival rates were estimated using the Kaplan-Meier method. Cox proportional hazards models were fit to test associations with recurrence. Recurrence to abdomen, the thoracic region, bone and brain developed in 185 (10%), 300 (16%), 134 (7%) and 81 (4%) patients, respectively. Positive surgical margins, 2003 TNM stage, size, grade and necrosis were significantly associated with abdominal recurrence in a multivariate setting. These same features, except surgical margins, were significantly associated with thoracic recurrence. The 2003 TNM stage, grade and necrosis were multivariately predictive of recurrence in bone. Scoring algorithms to predict the likelihood of disease recurrence to these sites and to guide the intensity of postoperative surveillance were developed using regression coefficients from the multivariate models. The proposed scoring algorithms resulted in excellent patient stratification. We present scoring algorithms based on multivariately significant predictors of site specific recurrence that can be used to tailor postoperative surveillance to the individual patient.


Tobacco mosaic virus infection results in an increase in recombination frequency and resistance to viral, bacterial, and fungal pathogens in the progeny of infected tobacco plants.
Our previous experiments showed that infection of tobacco (Nicotiana tabacum) plants with Tobacco mosaic virus (TMV) leads to an increase in homologous recombination frequency (HRF). The progeny of infected plants also had an increased rate of rearrangements in resistance gene-like loci. Here, we report that tobacco plants infected with TMV exhibited an increase in HRF in two consecutive generations. Analysis of global genome methylation showed the hypermethylated genome in both generations of plants, whereas analysis of methylation via 5-methyl cytosine antibodies demonstrated both hypomethylation and hypermethylation. Analysis of the response of the progeny of infected plants to TMV, Pseudomonas syringae, or Phytophthora nicotianae revealed a significant delay in symptom development. Infection of these plants with TMV or P. syringae showed higher levels of induction of PATHOGENESIS-RELATED GENE1 gene expression and higher levels of callose deposition. Our experiments suggest that viral infection triggers specific changes in progeny that promote higher levels of HRF at the transgene and higher resistance to stress as compared with the progeny of unstressed plants. However, data reported in these studies do not establish evidence of a link between recombination frequency and stress resistance.


Differential Sensitivity of Myeloid and Lymphoid Cell Populations to Apoptosis in Peritoneal Cavity of Mice with Model Larval Mesocestoides Vogae Infection.
The metacestode stage of the tapeworm Mesocestoides vogae (M. vogae) has the ability of asexual growth in the peritoneal cavity of rodents and other intermediate hosts without restriction. Early immunological events have decisive role in the establishment of infection. In the present study we investigated the kinetic of myeloid and lymphoid cell populations and the proportions of cells undergoing apoptosis in peritoneal cavities of mice within the first month after oral infection with M. vogae larvae. Proportions of cell phenotypes and apoptotic cells were examined by flow cytometry and by microscopical analysis of cells following May/Grünwald staining and fluorescent stain Hoechst 33234, respectively. Total numbers of peritoneal cells increased and their distribution changed towards accumulation of myelo-monocytic cell lineage in the account of reduced proportions of lymphoid cells. CD4+ T cell subpopulations were more abundant than CD8+ and their proportions elevated within two weeks post infection (p.i.) which was followed by a significant decline. Expression level of CD11c marker on myelo-monocytic cells revealed phenotype heterogeneity and proportions of cells with low and medium expression elevated from day 14 p.i. along with concurrent very low presence of CD11chigh phenotype. Lymphoid cell population was highly resistant to apoptosis but elevated proportions of myeloid cells were in early/late stage of apoptosis. Apoptosis was detected in a higher number of adherent cells from day 14 p.i. onwards as evidenced by nuclear fluorescent staining. By contrast, cells adherent to larvae, mostly macrophages and eosinophils, did not have fragmented nuclei. Our data demonstrated that apoptosis did not account for diminished population of peritoneal lymphoid cells and substantial proportions of myeloid cells seem to be more susceptible to apoptotic turnover in peritoneal cavity of mice with ongoing M. vogae infection, suggesting their important role in the host-parasite interactions.


Computer-detected patterns of electroencephalographic delta activity during and after extended sleep.
Delta (0.5 to 3 hertz) waves are the electroencephalographic hallmark of human sleep. We measured their rate of production during and following an extended night of sleep. On the extended night, we confirmed previous observations of a linear decline in delta wave production across the first four periods of non-rapid-eye-movement (non-REM) sleep. An asymptote was reached in the fifth non-REM period, perhaps signifying that sleep processes reached completion. On the day after the extended night, subjects were allowed to remain awake 3.6 hours less than normal. During the next sleep session, amplitude and number of delta waves in non-REM periods 1 and 3 were significantly reduced. These findings illustrate the value of computer analysis of electroencephalographic waveforms in sleep. Systematic measurement of the amount and distribution of these waveforms as a function of preceding waking duration should provide clues to the kinetics of the metabolic processes underlying sleep.


Molecular mechanisms regulating wound repair: Evidence for paracrine signaling from corneal epithelial cells to fibroblasts and immune cells following transient epithelial cell treatment with Mitomycin C.
In this paper, we use RNAseq to identify senescence and phagocytosis as key factors to understanding how mitomyin C (MMC) stimulates regenerative wound repair. We use conditioned media (CM) from untreated (CMC) and MMC treated (CMM) human and mouse corneal epithelial cells to show that corneal epithelial cells indirectly exposed to MMC secrete elevated levels of immunomodulatory proteins including IL-1α and TGFβ1 compared to cells exposed to CMC. These factors increase epithelial and macrophage phagocytosis and promote ECM turnover. IL-1α supplementation can increase phagocytosis in control epithelial cells and attenuate TGFβ1 induced αSMA expression by corneal fibroblasts. Yet, we show that epithelial cell CM contains factors besides IL-1α that regulate phagocytosis and αSMA expression by fibroblasts. Exposure to CMM also impacts the activation of bone marrow derived dendritic cells and their ability to present antigen. These in vitro studies show how a brief exposure to MMC induces corneal epithelial cells to release proteins and other factors that function in a paracrine way to enhance debris removal and enlist resident epithelial and immune cells as well as stromal fibroblasts to support regenerative and not fibrotic wound healing.


How Physically Active Are People Following Stroke? Systematic Review and Quantitative Synthesis.
Mobility limitations are common following stroke and frequently lead to poor participation in physical activity (PA). The purpose of this study was to describe PA across the various stages following stroke (acute, subacute, and chronic). Searches were conducted in 5 databases. Eligible studies included participants with stroke whose PA was quantitatively measured for at least 4 hours in a single session. Two reviewers independently reviewed titles and abstracts. One reviewer extracted data and assessed quality using the Downs and Black checklist. Weighted means were calculated for PA outcomes. Searches yielded 103 eligible papers including 5306 participants aged 21 to 96 years. Devices (eg, activity monitors) were used in 73 papers, and behavioral mapping (observational monitoring) in 30. Devices show that people with stroke took on average 5535 steps per day (n = 406, 10 studies) in the subacute phase and 4078 steps (n = 1280, 32 studies) in the chronic phase. Average daily walking duration (% measured time) was higher in the chronic phase (9.0%, n = 100) than subacute (1.8%, n = 172), and sedentary time was >78% regardless of time post stroke. Acute data were lacking for these variables. Matched healthy individuals took an average of 8338 steps per day (n = 129). Behavioral mapping showed time in bed was higher in the acute than subacute phase (mean 45.1% versus 23.8%), with similar time spent sitting (mean 37.6% versus 32.6%). Limitations of this review include not pooling data reported as medians. Physical activity levels do not meet guidelines following stroke. Time spent inactive and sedentary is high at all times. Increasing PA and developing standardized activity targets may be important across all stages of stroke recovery.


Modeling Intestinal Epithelial Response to Interferon-γ in Induced Pluripotent Stem Cell-Derived Human Intestinal Organoids.
Human intestinal organoids (HIOs) are increasingly being used to model intestinal responses to various stimuli, yet few studies have confirmed the fidelity of this modeling system. Given that the interferon-gamma (IFN-γ) response has been well characterized in various other cell types, our goal was to characterize the response to IFN-γ in HIOs derived from induced pluripotent stem cells (iPSCs). To achieve this, iPSCs were directed to form HIOs and subsequently treated with IFN-γ. Our results demonstrate that IFN-γ phosphorylates STAT1 but has little effect on the expression or localization of tight and adherens junction proteins in HIOs. However, transcriptomic profiling by microarray revealed numerous upregulated genes such as IDO1, GBP1, CXCL9, CXCL10 and CXCL11, which have previously been shown to be upregulated in other cell types in response to IFN-γ. Notably, "Response to Interferon Gamma" was determined to be one of the most significantly upregulated gene sets in IFN-γ-treated HIOs using gene set enrichment analysis. Interestingly, similar genes and pathways were upregulated in publicly available datasets contrasting the gene expression of in vivo biopsy tissue from patients with IBD against healthy controls. These data confirm that the iPSC-derived HIO modeling system represents an appropriate platform to evaluate the effects of various stimuli and specific environmental factors responsible for the alterations in the intestinal epithelium seen in various gastrointestinal conditions such as inflammatory bowel disease.


Maintenance of certification: current attitudes of members of the American Society of Neuroradiology.
The maintenance of certification (MOC) process has begun in radiology, and many physicians will be affected by it. We sought to assess the compliance with and knowledge of the MOC steps by American Society of Neuroradiology (ASNR) members. An on-line survey was distributed via e-mail to the members of the ASNR for whom e-mail addresses were available. The survey addressed 3 components of the MOC currently implemented: 1) MOC cognitive examinations, 2) self-assessment modules (SAMs), and 3) continuing medical education (CME) credits. The response rate was 1020/2662 (38.3%). Of those responding, 11% stated that they either do not support the MOC examination (8%) or were unaware of it (3%), 21.4% of respondents have completed an SAM module, but >30% were unaware that they had to complete SAMs or did not know where they were offered. Many members will receive most of their 25 required CME hours for 2007 from sources besides the ASNR annual meeting. Of the small proportion of respondents who made comments (247/1020, 24.2%), those about the MOC process were favorable in 6.1% (15/247), unfavorable in 46.6% (115/247), and neutral in 47.4% (117/247). The MOC process remains poorly understood, with limited compliance. The radiology societies should spend additional effort publicizing the requirements and offering support and products aimed at allowing their members to achieve compliance in a reasonable cost-effective fashion.


Shortest exposure time possible with LED curing lights.
To investigate the shortest exposure time of different light emitting diode (LED)-curing devices for different resin composites in a clinically relevant laboratory model. Nine LED curing devices (Bluephase, Bluephase 16i, Bluephase G2, Bluephase 20i/Ivoclar Vivadent, DEMI/sds Kerr, Elipar FreeLight 2, Elipar S10/3M ESPE, Radii plus/SDI, mini LED Autofocus/Satelec) were investigated to polymerize Tetric EvoCeram (TEC) and Filtek Supreme XT B (FS) in the shades A1, A2, A3, A3.5, and A4. The Bluephase 20i was investigated in its high power and turbo modes. Stainless steel molds (Ø = 5 mm, h = 6 mm, six resin composite test samples per curing device, material, and shade) were filled in three increments of 2 mm thickness each and incrementally exposed with the light guide tip in a 7 mm distance from the bottom side to simulate a Class II curing situation. Surface hardness was measured 10 minutes post exposure at bottom surfaces of resin samples (n=3 per sample). A bottom/top-surface hardness ratio of 80% of a reference surface hardness cured at a zero-distance (40 seconds) was defined as clinically acceptable for safe curing. A statistical analysis (Excel) was carried out. To ensure a ratio in surface hardness of at least 80% the minimal exposure time(s) were: Elipar FreeLight 2, DEMI: TEC and FS: 10 seconds for all shades, except DEMI FS A4: 20 seconds. Elipar S10: 10 seconds for both, TEC and FS shades A2-A4 but 5 seconds for shades A1. Bluephase, Bluephase 16i and Bluephase G2: FS: 10 seconds for shades A1-A3.5; 20 seconds for shade A4. TEC: Bluephase: A1-A3.5: 10 seconds, A4: 20 seconds. Bluephase 16i: A1-A3: 10 seconds; A3.5 + A4: 30 seconds. Bluephase G2: A1-A3: 10 seconds; A3.5 + A4: 20 seconds. Bluephase 20i-HIP: 10 seconds for all shades of TEC and FS, Bluephase 20i-Turbo: 10 seconds for all shades of TEC but 5 seconds for all shades of FS: Radii plus: TEC A1-A3: 10 seconds; A3.5+A4: 20 seconds. FS A1, A2 and A4: 10 seconds; A3+A3.5: 20 seconds. Mini LED Autofocus: TEC A1, A3, A3.5: 10 seconds; A2: 15 seconds; A4: 20 seconds. FS A1: 5 seconds; A2-A4: 10 seconds. In its turbo mode with a 5-second exposure time, the Bluephase 20i was able to polymerize all shades of FS, but not of TEC. For the Elipar S10 and the Mini LED Autofocus this was also possible for the A1 shade of FS; for Elipar S10 additionally for TEC. The higher power of the Bluephase G2 and the S10 LED allowed the use of an enhanced light guide tip diameter while the exposure time was not affected compared to their predecessors equipped with an 7.5 or 8 mm light guide tip diameter respectively. Nevertheless, 10 seconds should be the minimal exposure time recommended for lighter shades under optimal circumstances.


Financial toxicity and its implication on quality of life in patients attending the palliative care department in a regional cancer centre: an observational study.
In India the cancer burden for 2021 was 26.7 million disability-adjusted life years (DALYs), and this is expected to increase to 29.8 million in 2025 [1]. According to the World Health Organisation (WHO), cancer is a leading cause of death worldwide, accounting for one in six deaths. As per WHO, palliative care is a strategy that assists both adults and children along with their families in dealing with life-threatening illnesses. Currently, only 14% of those in need of pain and palliative (P&P) care receive it globally (WHO, 2020). Financial toxicity (FT) is the term used to describe the negative effects that an excessive financial burden resulting from cancer have on patients, their families, and society [2]. Addressing this gap will require significant adjustments to both demand- and supply-side policies to ensure accessible and equitable cancer care in India [3]. Measuring FT along with health-related quality of life (HRQoL) represents a clinically relevant and patient-centred approach [4]. To estimate FT and its association with quality of life (QoL). This was an observational descriptive study conducted among cancer patients recommended for P&P care. Scores were estimated from September 2022 to February 2023 using official tools: the Functional Assessment for Chronic illness Treatment Compressive Score for Financial Toxicity (FACIT-COST) and the European Organisation for Research and Treatment of Cancer (EORTC) Quality of life Questionnaires for Cancer (QLQ30). From 150 patients (70 males and 80 females, mean age 54.96 ± 13.5 years), 92.6% suffered from FT. Eleven patients (7.3%) were under FT grade 0, 41 (27.3%) were FT grade 1, 98 (65.3%) were FT grade 2, and no patients were under FT grade 3. At criterial alpha 0.05 (95%CI), FT and the global score for HRQoL showed an association. Among inpatient department (IPD) expenses, medication bills contributed the greatest expense at 33%, and among outpatient department (OPD) expenses treatment expenses contributed 50% of the total. Breast cancer (30 cases, 20%) and oral cancer (26 cases, 17.3%) were the most frequent cancers. FT measured using the COST tool showed an association with HRQoL. This paper refers to the insurance policies available for cancer patients irrespective of P&P care treatment.


Large-scale modeling of epileptic seizures: scaling properties of two parallel neuronal network simulation algorithms.
Our limited understanding of the relationship between the behavior of individual neurons and large neuronal networks is an important limitation in current epilepsy research and may be one of the main causes of our inadequate ability to treat it. Addressing this problem directly via experiments is impossibly complex; thus, we have been developing and studying medium-large-scale simulations of detailed neuronal networks to guide us. Flexibility in the connection schemas and a complete description of the cortical tissue seem necessary for this purpose. In this paper we examine some of the basic issues encountered in these multiscale simulations. We have determined the detailed behavior of two such simulators on parallel computer systems. The observed memory and computation-time scaling behavior for a distributed memory implementation were very good over the range studied, both in terms of network sizes (2,000 to 400,000 neurons) and processor pool sizes (1 to 256 processors). Our simulations required between a few megabytes and about 150 gigabytes of RAM and lasted between a few minutes and about a week, well within the capability of most multinode clusters. Therefore, simulations of epileptic seizures on networks with millions of cells should be feasible on current supercomputers.


[The significance of clinical guidelines for rehabilitation].
Clinical practice guidelines are relevant to all parties involved in the health system. For rehabilitation under the German pension insurance scheme, there are two main aspects: the integration of rehabilitation into the curative guidelines in terms of "local tailoring" on the one hand and the development of guidelines for rehabilitative processes, demand-oriented control of rehabilitation access, and rehabilitative aftercare on the other hand. The elaboration of effective standards is aimed at avoiding over-provision, under-provision or misdirected provision of care and, simultaneously, at ensuring that quality assured treatment is offered to the rehabilitees. Also, it is intended to increasingly implement evidence-based medicine in a sector of the health system in which research has so far been underrepresented. Implementation of guidelines in the rehabilitative sector will allow to disseminate existing knowledge in targeted manner, to systematically fill the gaps and to broaden the knowledge base as a whole. Furthermore, guidelines can facilitate integration of the different sectors in health care provision by operationalising the interfaces both with curative medicine and primary prevention. Throughout the process of guideline development for rehabilitation the specific characteristics of this sector must be kept in mind. Since therapeutic interventions are multidisciplinary and multimodal in nature guidelines have to be comprehensible and applicable for all members of the multiprofessional team. Corresponding to the relative paucity in rehabilitation research there is no sufficient evidence base for numerous therapeutic interventions. Accordingly, guidelines in rehabilitation will--initially--consist of a mixture of evidence- and consensus-based recommendations. Also, the specific goal of rehabilitation under the German pension insurance scheme, namely maintenance or recovery of the capacity at work, has to be borne in mind. There are many initiatives by the providers of rehabilitation as well as the scientific medical societies to develop and implement rehabilitative clinical practice guidelines, e. g. the guidelines programme of the BfA (Federal Insurance Institute for Salaried Employees), which is aimed at developing rehabilitation process guidelines for selected indications, the guidelines activities of the VDR (Federation of German Pension Insurance Institutes), and the input of the "Guidelines" commission of the DGRW (German Society of Rehabilitation Science). It is hoped that in the years to come the parties involved in German health care provision will be open to the advantages of clinical practice guidelines. Rehabilitation under the German pension insurance scheme, with respect to its experience with quality assurance, its responsibilities for structure and concept and a growing acceptance on the part of care providers, already holds a well-founded starting position.


Response of the hypothalamo-neurohypophyseal axis (AVP system) and the kidney to salt load in young propylthiouracil-treated rats.
The development of the ability of the kidney to concentrate urine was studied in normal and propylthiouracil-treated rats by measuring urinary sodium concentration and osmolarity at different ages. It was shown that the normal animals, but not the PTU-treated ones were able to concentrate urine at 35 days of age. The response of the hypothalamo-neurohypophyseal axis (AVP system) and that of the kidney were investigated in the two categories of animals at 35 days of age by measuring concomitantly the AVP content of the hypothalamus and neurohypophysis, the AVP plasma concentration and the natremia and plasma osmolarity at various intervals after intraperitoneal injection of a 5% NaCl solution. In normal, as well as in PTU-treated rats, salt load did not lead to significant modifications of the hypothalamic AVP content. In comparison with normal rats, the neurohypophysis of the PTU-treated ones released AVP more slowly, but with a similar amplitude. In normal rats, the plasma AVP concentration was already maximal 30 min after salt load and then decreased and returned to the normal value at 2 hrs; at the same time, the natremia and plasma osmolarity also recovered their normal value. In contrast, the plasma AVP concentration as well as the natremia remained high 1 h 30 after salt load in PTU-treated rats. It is concluded that PTU-treated young rat is unable to compensate the salt load in normal delays. Beside the slowing in AVP release by neurohypophysis and decreased AVP plasma level, the responsiveness of the kidney seems to be altered.


A Non-Invasive Prediction Model for Non-Alcoholic Fatty Liver Disease in Adults with Type 2 Diabetes Based on the Population of Northern Urumqi, China.
High prevalence of non-alcoholic fatty liver disease (NAFLD) occurs in type 2 diabetes mellitus (T2DM), and about 13% of diabetic patients eventually die of liver cirrhosis or liver cancer. The purpose of our research was to develop a non-invasive predictive model of NAFLD in adults with T2DM. Adult patients diagnosed with T2DM during physical examination in 2018 in Urumqi were recruited, in total 40,921 cases. We chose questionnaire and physical measurement variables to build a simple, low-cost model. Variables were selected by the least absolute shrinkage and selection operator regression (LASSO). The features chosen by LASSO were used to build the nomogram prediction model of NAFLD. The receiver operating curve (ROC) and calibration were used for model validation. Determinants in the nomogram included age, ethnicity, sex, exercise, smoking, dietary ratio, heart rate, systolic blood pressure (SBP), BMI, waist circumference, and atherosclerotic vascular disease (ASCVD). The area under ROC of developing group and validation group was 0.756 (95% confidence interval 0.750-0.761) and 0.755 (95% confidence interval 0.746-0.763), respectively, and the P values of the two calibration curves were 0.694 and 0.950, suggesting that the nomogram had good disease recognition ability and calibration. A nomogram constructed with accuracy can calculate the possibility of NAFLD in adults with T2DM. If validated externally, this tool could be utilized as a non-invasive method to diagnose non-alcoholic fatty liver in adults with T2DM.


A Cognition-Related Neural Oscillation Pattern, Generated in the Prelimbic Cortex, Can Control Operant Learning in Rats.
The prelimbic (PrL) cortex constitutes one of the highest levels of cortical hierarchy dedicated to the execution of adaptive behaviors. We have identified a specific local field potential (LFP) pattern generated in the PrL cortex and associated with cognition-related behaviors. We used this pattern to trigger the activation of a visual display on a touch screen as part of an operant conditioning task. Rats learned to increase the presentation rate of the selected θ to β-γ (θ/β-γ) transition pattern across training sessions. The selected LFP pattern appeared to coincide with a significant decrease in the firing of PrL pyramidal neurons and did not seem to propagate to other cortical or subcortical areas. An indication of the PrL cortex's cognitive nature is that the experimental disruption of this θ/β-γ transition pattern prevented the proper performance of the acquired task without affecting the generation of other motor responses. The use of this LFP pattern to trigger an operant task evoked only minor changes in its electrophysiological properties. Thus, the PrL cortex has the capability of generating an oscillatory pattern for dealing with environmental constraints. In addition, the selected θ/β-γ transition pattern could be a useful tool to activate the presentation of external cues or to modify the current circumstances.SIGNIFICANCE STATEMENT Brain-machine interfaces represent a solution for physically impaired people to communicate with external devices. We have identified a specific local field potential pattern generated in the prelimbic cortex and associated with goal-directed behaviors. We used the pattern to trigger the activation of a visual display on a touch screen as part of an operant conditioning task. Rats learned to increase the presentation rate of the selected field potential pattern across training. The selected pattern was not modified when used to activate the touch screen. Electrical stimulation of the recording site prevented the proper performance of the task. Our findings show that the prelimbic cortex can generate oscillatory patterns that rats can use to control their environment for achieving specific goals.


Simultaneous phylogeny reconstruction and multiple sequence alignment.
A phylogeny is the evolutionary history of a group of organisms. To date, sequence data is still the most used data type for phylogenetic reconstruction. Before any sequences can be used for phylogeny reconstruction, they must be aligned, and the quality of the multiple sequence alignment has been shown to affect the quality of the inferred phylogeny. At the same time, all the current multiple sequence alignment programs use a guide tree to produce the alignment and experiments showed that good guide trees can significantly improve the multiple alignment quality. We devise a new algorithm to simultaneously align multiple sequences and search for the phylogenetic tree that leads to the best alignment. We also implemented the algorithm as a C program package, which can handle both DNA and protein data and can take simple cost model as well as complex substitution matrices, such as PAM250 or BLOSUM62. The performance of the new method are compared with those from other popular multiple sequence alignment tools, including the widely used programs such as ClustalW and T-Coffee. Experimental results suggest that this method has good performance in terms of both phylogeny accuracy and alignment quality. We present an algorithm to align multiple sequences and reconstruct the phylogenies that minimize the alignment score, which is based on an efficient algorithm to solve the median problems for three sequences. Our extensive experiments suggest that this method is very promising and can produce high quality phylogenies and alignments.


Development and Characterization of Novel Rat Anti-mERβ Sera.
Estrogens regulate normal sexual and reproductive development in females. Their actions are mediated mainly by estrogen receptor (ER)α and ERβ. Understanding the function of ERs necessitates knowing their cellular location and protein partners, which, in turn, requires reliable and specific antibodies. Several antibodies are available for ERα; however, discrepancies in immunoreactivity have been reported for ERβ. Here, we have developed antisera for mouse ERβ (mERβ) using a specific C-terminal 18-amino acid peptide conjugated to mariculture keyhole limpet hemocyanin. Sprague Dawley rats were immunized, and the resulting antisera were characterized by Western blot analysis of nuclear extracts from tissues of wild-type (WT) mice, and mice genetically modified to lack either ERα (CERαKO) or ERβ (CERβKO). An approximately 56-kDa protein was detected in the hypothalamus, uterus, ovary, mammary gland, testes, and epididymis of WT mice, consistent with the predicted molecular size of ERβ. In addition, the same protein band was identified in in vitro synthesized mERβ protein and in the mammary glands of CERαKO mice. The approximately 56-kDa protein was not observed in in vitro synthesized mERα protein or in any tissue examined in the CERβKO mice. Immunohistochemistry using the antisera revealed ERβ staining in the granulosa cells of WT ovaries and in the mediobasal hypothalamus, paraventricular nucleus, and cerebral cortex in the WT adult mouse brain. These data suggest that the novel rat anti-mERβ sera are specific to ERβ to allow investigators to explore to cellular and physiological role of ERβ in the brain and other mouse tissues.


Longitudinal proteomic profiling of dialysis patients with COVID-19 reveals markers of severity and predictors of death.
End-stage kidney disease (ESKD) patients are at high risk of severe COVID-19. We measured 436 circulating proteins in serial blood samples from hospitalised and non-hospitalised ESKD patients with COVID-19 (n = 256 samples from 55 patients). Comparison to 51 non-infected patients revealed 221 differentially expressed proteins, with consistent results in a separate subcohort of 46 COVID-19 patients. Two hundred and three proteins were associated with clinical severity, including IL6, markers of monocyte recruitment (e.g. CCL2, CCL7), neutrophil activation (e.g. proteinase-3), and epithelial injury (e.g. KRT19). Machine-learning identified predictors of severity including IL18BP, CTSD, GDF15, and KRT19. Survival analysis with joint models revealed 69 predictors of death. Longitudinal modelling with linear mixed models uncovered 32 proteins displaying different temporal profiles in severe versus non-severe disease, including integrins and adhesion molecules. These data implicate epithelial damage, innate immune activation, and leucocyte-endothelial interactions in the pathology of severe COVID-19 and provide a resource for identifying drug targets.


Dose-dense temozolomide for newly diagnosed glioblastoma: a randomized phase III clinical trial.
Radiotherapy with concomitant and adjuvant temozolomide is the standard of care for newly diagnosed glioblastoma (GBM). O(6)-methylguanine-DNA methyltransferase (MGMT) methylation status may be an important determinant of treatment response. Dose-dense (DD) temozolomide results in prolonged depletion of MGMT in blood mononuclear cells and possibly in tumor. This trial tested whether DD temozolomide improves overall survival (OS) or progression-free survival (PFS) in patients with newly diagnosed GBM. This phase III trial enrolled patients older than age 18 years with a Karnofsky performance score of ≥ 60 with adequate tissue. Stratification included clinical factors and tumor MGMT methylation status. Patients were randomly assigned to standard temozolomide (arm 1) or DD temozolomide (arm 2) for 6 to 12 cycles. The primary end point was OS. Secondary analyses evaluated the impact of MGMT status. A total of 833 patients were randomly assigned to either arm 1 or arm 2 (1,173 registered). No statistically significant difference was observed between arms for median OS (16.6 v 14.9 months, respectively; hazard ratio [HR], 1.03; P = .63) or median PFS (5.5 v 6.7 months; HR, 0.87; P = .06). Efficacy did not differ by methylation status. MGMT methylation was associated with improved OS (21.2 v 14 months; HR, 1.74; P < .001), PFS (8.7 v 5.7 months; HR, 1.63; P < .001), and response (P = .012). There was increased grade ≥ 3 toxicity in arm 2 (34% v 53%; P < .001), mostly lymphopenia and fatigue. This study did not demonstrate improved efficacy for DD temozolomide for newly diagnosed GBM, regardless of methylation status. However, it did confirm the prognostic significance of MGMT methylation. Feasibility of large-scale accrual, prospective tumor collection, and molecular stratification was demonstrated.


Prognostic Value of Baseline Tumor Burden and Tumor Dissemination Extracted From 18 F-FDG PET/CT in a Cohort of Adult Patients With Early or Advanced Hodgkin Lymphoma.
We aimed to assess the prognostic value of baseline tumor burden and dissemination parameters extracted from 18 F-FDG PET/CT in patients with early or advanced Hodgkin lymphoma (HL) treated with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) or escalated BEACOPP (increased bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone). Patients aged ≥18 years with classical Hodgkin lymphoma were retrospectively included. Progression-free survival (PFS) analysis of dichotomized clinicobiological and PET/CT parameters (SUV max , TMTV, TLG, D max , and D bulk ) was performed. Optimal cutoff values for quantitative metrics were defined as the values maximizing the Youden index from receiver operating characteristic analysis. PFS rates were estimated with Kaplan-Meier curves, and the log-rank test was used to assess statistical significance. Hazard ratios were calculated using Cox proportional hazards models. With a median age of 32 years, 166 patients were enrolled. A total of 111 patients had ABVD or ABVD-like treatment with or without radiotherapy and 55 patients with escalated BEACOPP treatment. The median follow-up was 55 months. Only International Prognostic Score (IPS >1), TMTV >107 cm 3 , and TLG >1628 were found to be significant prognostic factors for PFS on univariate analysis. Multivariate analysis revealed that IPS and TLG were independently prognostic and, combined, identified 4 risk groups ( P < 0.001): low (low TLG and low IPS; 4-year PFS, 95%), intermediate-low (high IPS and low TLG; 4-year PFS, 79%), intermediate-high (low IPS and high TLG; 4-year PFS, 78%), and high (high TLG and high IPS; 4-year PFS, 71%). Combining baseline TLG with IPS could improve PFS prediction.


The role of extracorporeal membrane oxygenation in donation after circulatory death.
Donor scarcity and the increased need for organ transplantation has prompted the development of an alternative source of donors to the more conventional brain dead donor. While in a Beating-Heart donor, abdominal and intrathoracic organs are perfused, in a non-beating heart donor (NHBD, or DCD), perfusion should be maintained, after confirmation of death, by means of ECMO and inflation of intra-aortic balloon accordingly to the localization of the organs that should be transplanted. In this setting, ECMO allows selective perfusion of the organs which should be transplanted ("compartmental ECMO"). The present review is aimed at summarizing the rationale for ECMO use in organ donation in DCD and the available evidence on this topic, as well as available evidence (in clinical studies) on normothermic organ preservation using ECMO in adults. Despite the fact that available studies suffer from methodological limitations (small cohorts, retrospective analysis, not always comparative), they all reach the same conclusion: the concept of extracorporeal support with oxygenation in DCD seems very promising since it has been reported to increase the available organ supply by approximately 20% to 25%2 by increasing the number of donors by approximately 33%. Centres with ECMO facilities should implement local programmes for donation after cardiac death (both in the emergency department and intensive care) using ECMO taking into account that this technique has been proven to increase donor pool.


Robust super-resolution depth imaging via a multi-feature fusion deep network.
The number of applications that use depth imaging is increasing rapidly, e.g. self-driving autonomous vehicles and auto-focus assist on smartphone cameras. Light detection and ranging (LIDAR) via single-photon sensitive detector (SPAD) arrays is an emerging technology that enables the acquisition of depth images at high frame rates. However, the spatial resolution of this technology is typically low in comparison to the intensity images recorded by conventional cameras. To increase the native resolution of depth images from a SPAD camera, we develop a deep network built to take advantage of the multiple features that can be extracted from a camera's histogram data. The network is designed for a SPAD camera operating in a dual-mode such that it captures alternate low resolution depth and high resolution intensity images at high frame rates, thus the system does not require any additional sensor to provide intensity images. The network then uses the intensity images and multiple features extracted from down-sampled histograms to guide the up-sampling of the depth. Our network provides significant image resolution enhancement and image denoising across a wide range of signal-to-noise ratios and photon levels. Additionally, we show that the network can be applied to other data types of SPAD data, demonstrating the generality of the algorithm.


Occurrence of otitis media in children and assessment of treatment options.
Otitis media is a more frequent occurrence in children, and the disease may progress from an acute to chronic state if appropriate and timely intervention is not initiated. A total of 212 children aged 6 months to 10 years were examined and treated for otitis media, in a 13-month hospital-based study. Acute otitis media was diagnosed in 130 (61.3 per cent) of the patients. There were 82 (38.7 per cent) chronic suppurative otitis media cases. The incidence of acute otitis media and chronic suppurative otitis media in the first year of life was 54.6 per cent and 45.1 per cent respectively. Chronic suppurative otitis media patients were assigned to one of three treatment groups. Recovery occurred in 70.4 per cent of amoxicillin-treated patients, in 88.9 per cent of amoxicillin-clavulanic acid treated patients and in 96.4 per cent of culture and antibiotic sensitivity test patients. Relapses were seen only in the amoxicillin (five cases) and amoxicillin-clavulanic acid (two cases) groups. The success rate in patients treated with antibiotics makes this option mandatory for an established diagnosis.


The structure, stability and pheromone binding of the male mouse protein sex pheromone darcin.
Mouse urine contains highly polymorphic major urinary proteins that have multiple functions in scent communication through their abilities to bind, transport and release hydrophobic volatile pheromones. The mouse genome encodes for about 20 of these proteins and are classified, based on amino acid sequence similarity and tissue expression patterns, as either central or peripheral major urinary proteins. Darcin is a male specific peripheral major urinary protein and is distinctive in its role in inherent female attraction. A comparison of the structure and biophysical properties of darcin with MUP11, which belongs to the central class, highlights similarity in the overall structure between the two proteins. The thermodynamic stability, however, differs between the two proteins, with darcin being much more stable. Furthermore, the affinity of a small pheromone mimetic is higher for darcin, although darcin is more discriminatory, being unable to bind bulkier ligands. These attributes are due to the hydrophobic ligand binding cavity of darcin being smaller, caused by the presence of larger amino acid side chains. Thus, the physical and chemical characteristics of the binding cavity, together with its extreme stability, are consistent with darcin being able to exert its function after release into the environment.


A liquid chromatography-tandem mass spectrometry method for the simultaneous determination of exemestane and its metabolite 17-dihydroexemestane in human plasma.
A simple and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the quantitation of exemestane (Exe) and its main metabolite 17-dihydroexemestane (DhExe) in human plasma. The analytes were extracted by protein precipitation with acetonitrile, containing stable 13C-labelled Exe (13C3-Exe) as internal standard, and measured by LC-MS/MS. The best chromatographic separation of the analytes from the interferences was achieved by using a Phenyl column operating under isocratic regime conditions. The total chromatographic runtime was 5.0 min and the elution of Exe and DhExe occurred at 2.5 min and 2.9 min, respectively. Quantitation was performed by employing the positive electrospray ionization (ESI) technique and multiple reaction monitoring mode (MRM). The monitored precursor to product-ion transitions for Exe, DhExe and 13C3-Exe internal standard were m/z 297.0 --> 120.8, m/z 299.1 --> 134.9 and m/z 300.0 --> 123.2, respectively. The lower limit of quantitation (LLOQ) was 0.1 ng/ml for DhExe and 0.2 ng/ml for Exe. The method was linear up to 36-51 ng/ml with r2 > or = 0.998. The intra- and inter-assay precision were < or = 7.7% and 5.1% for Exe and < or = 8.1 and 4.9% for DhExe while deviations from nominal values were in the 1.5-13.2% and - 9.0-5.8% ranges for Exe and DhExe, respectively. The analytical method resulted robust and suitable for pharmacokinetic monitoring of Exe and its main metabolite during adjuvant therapy in patients with breast cancer.


Haemagglutination by bovine leukaemia virus.
Bovine leukaemia virus (BLV) was found to agglutinate mouse erythrocytes. Under optimal conditions, including the use of neuraminidase-treated erythrocytes, 200 microgram/ml of BLV purified from the supernatant fluid of BLV-infected bat cells had haemagglutinating titres of about 512 units. BLV haemagglutination was drastically affected by pH and temperature; maximum agglutination occurred at pH 6 and 4 degrees C. That the BLV haemagglutinin is a glycoprotein was suggested by the fact that trypsin, potassium periodate or neuraminidase, but not lipid solvents or phospholipase C, significantly reduced the haemagglutinating (HA) activity of purified BLV. Furthermore, purified BLV glycoprotein of mol. wt. 51 000 (gp51) had HA activity. The receptors for BLV on mouse erythrocytes were inactivated by proteolytic enzymes but not by sodium deoxycholate or potassium periodate. Neuraminidase treatment of erythrocytes increase their agglutinability fourfold. Haemagglutination is a relatively sensitive test for detecting BLV glycoprotein because 0.4 microgram/ml of glycoprotein can be detected by this method. The pH and temperature sensitivity of the BLV HA reaction and specificity for mouse erythrocytes distinguish BLV from that of equine infectious anaemia virus and murine leukaemia virus, the other C type retroviruses known to have HA activity.


Intraoperative Floppy Iris Syndrome: Updated Perspectives.
Almost fifteen years since its initial description, intraoperative floppy iris syndrome (IFIS) during phacoemulsification surgery remains a challenge for cataract surgeons in all its key aspects that include the stratification of the preoperative risk, preoperative prophylaxis treatment, surgery design and intraoperative management. Since its original association with tamsulosin intake, IFIS has been positively correlated with a plethora of risk factors which include: gender, age, hypertension, other a1-adrenergic receptor antagonists, finasteride, angiotensin II receptor inhibitors, benzodiazepines, antipsychotics, hypertension drugs and decreased dilated pupil diameter. The assessment and stratification of the preoperative risk is pivotal in screening patients prone to develop IFIS. For these patients, it is essential that preoperative prophylaxis, employment of necessary measures and surgical technique modifications are considered. A multidisciplinary approach of IFIS is a mandate, thus ophthalmologists, urologists and sometimes other specialties should cooperate to "educate" each other about the risks of their respective fields. They both must be aware of the joint statement on IFIS by the American Academy of Ophthalmology and the American Society of Cataract and Refractive Surgery which suggests either the initiation of tamsulosin after phacoemulsification or the use of a non-selective a1-ARA for benign prostatic hyperplasia treatment. In conclusion, awareness of the risk factors associated with IFIS and their detailed preoperative documentation is crucial in addressing IFIS. The lack of such an awareness can turn a routine, uneventful surgery into one with significant visual morbidity.


Ursolic Acid-Induced Apoptosis via Regulation of the PI3K/Akt and MAPK Signaling Pathways in Huh-7 Cells.
Ursolic acid (UA), is a kind of triterpene acid that exhibits wide biological properties. In this article, the effects of UA on apoptosis and the proliferation of human hepatoma Huh-7 cells were reported. The MTT results showed that cell viability of Huh-7 was reduced in a concentration and time-dependent effect. In addition, DAPI staining was used to detected condensation of chromatin in nucleus. Apoptotic cell population was examined using Annexin V/PI staining. The results showed that exposure to UA affected extrinsic and intrinsic pathways through, reduced expression of Bcl-2, Mcl-1, and TCTP; increased levels of the apoptotic proteins TNF-α, Fas, FADD, and Bax; and activation of cleaved caspase-3 and PARP. UA also inhibited the p-Akt and p38 MAPK signaling transduction pathways, and increased activity in the p-ERK signaling pathway. Taken together, UA inhibited the cell growth of Huh-7 cells and affected apoptosis, via regulated cellular signaling transduction.


[The determination of the level of resection of the esophagus taking into account its blood supply].
Inadequate blood supply is one of the major reasons of esophageal anastomosis incompetence. The authors have examined esophageal blood supply as regards of the operative technique. The esophageal vascular system was studied by the method of intraarterial impregnation in 40 cadavers. Two segments, crucial for esophageal anastomosis, have been determined: retropericardial segment in case of the lower esophageal artery ligation and the upper segment of the thoracic esophagus in case of its extreme mobilization in proximal direction and ligation of lower thyroid arteries. The results of 175 operations were analysed. The direct correlation between the frequency of anastomotic incompetence and the level of its formation was determined. In the zone with an inadequate blood supply the complication occurred in 4 patients of 25 (16%). In other cases the rate of incompetence was 3.2%. No cases of incompetence were observed in 61 patients after anastomosis was performed with due regard for esophageal blood supply.


Determining in-patient diabetes treatment satisfaction in the UK--the DIPSat study.
To measure in-patient diabetes treatment satisfaction and its relationship to in-patient diabetes care. In a cross-sectional study, diabetes in-patient specialist nurses at 58 UK hospitals asked insulin-treated in-patients with diabetes to complete the recently updated Diabetes Treatment Satisfaction Questionnaire for In-patients and a general questionnaire; 1319 in-patients completed these questionnaires. Satisfaction with the general diabetes treatment items in the Diabetes Treatment Satisfaction Questionnaire for In-patients was high, but there were high levels of extreme dissatisfaction with meal choices, meal quality and lack of similarity of hospital meals to normal domestic choices--23% would never or rarely have made similar meal choices at home. Hyperglycaemia or hypoglycaemia was reported for much of the in-patient stay (20% and 7%, respectively) and 26% reported at least one severe hypoglycaemic episode; these groups had lower satisfaction with the timing of medication in relation to meals (P < 0.003). More frequent in-patient hyperglycaemia or hypoglycaemia were associated with significantly poorer overall satisfaction scores and negative well-being scores (both P < 0.0001). Previous experience of a multiple daily insulin injection regimen was associated with more dissatisfaction than other regimens (P < 0.01). Multiple regression models explained 36% of variability in overall treatment satisfaction, with most (22.4%) accounted for by satisfaction with time spent with a diabetes in-patient specialist nurse (P < 0.0001). Self-administration of insulin was independently associated with higher treatment satisfaction (P < 0.006) in this model. The DIPSat programme describes the complex relationships between diabetes in-patient treatment satisfaction and in-patient diabetes care.


Myocardial infarction does not preclude electrical and hemodynamic benefits of cardiac resynchronization therapy in dyssynchronous canine hearts.
Several studies suggest that patients with ischemic cardiomyopathy benefit less from cardiac resynchronization therapy. In a novel animal model of dyssynchronous ischemic cardiomyopathy, we investigated the extent to which the presence of infarction influences the short-term efficacy of cardiac resynchronization therapy. Experiments were performed in canine hearts with left bundle branch block (LBBB, n=19) and chronic myocardial infarction, created by embolization of the left anterior descending or left circumflex arteries followed by LBBB (LBBB+left anterior descending infarction [LADi; n=11] and LBBB+left circumflex infarction [LCXi; n=7], respectively). Pacing leads were positioned in the right atrium and right ventricle and at 8 sites on the left ventricular (LV) free wall. LV pump function was measured using the conductance catheter technique, and synchrony of electrical activation was measured using epicardial mapping and ECG. Average and maximal improvement in electric resynchronization and LV pump function by right ventricular+LV pacing was similar in the 3 groups; however, the site of optimal electrical and mechanical benefit was LV apical in LBBB hearts, LV midlateral in LBBB+LCXi hearts and LV basal-lateral in LBBB+LADi hearts. The best site of pacing was not the site of latest electrical activation but that providing the largest shortening of the QRS complex. During single-site LV pacing the range of atrioventricular delays yielding > or =70% of maximal hemodynamic effect was approximately 50% smaller in infarcted than noninfarcted LBBB hearts (P<0.05). Cardiac resynchronization therapy can improve resynchronization and LV pump function to a similar degree in infarcted and noninfarcted hearts. Optimal lead positioning and timing of LV stimulation, however, require more attention in the infarcted hearts.


Computational studies on ethylene addition to nickel bis(dithiolene).
The density functionals B3LYP, B3PW91, BMK, HSE06, LC-ωPBE, M05, M06, O3LYP, TPSS, ω-B97X, and ω-B97XD are used to optimize key transition states and intermediates for ethylene addition to Ni(edt)(2) (edt = S(2)C(2)H(2)). The efficacy of the basis sets 6-31G**, 6-31++G**, cc-pVDZ, aug-cc-pVDZ, cc-pVTZ, and aug-cc-pVTZ is also examined. The geometric parameters optimized with different basis sets and density functionals are similar and agree well with experimental values. The ω-B97XD functional gives relative energies closest to those from CCSD, while M06 and HSE06 yield results close to those from CCSD(T). CASSCF and CASSCF-PT2 calculation results are also given. Variation of the relative energies from different density functionals appears to arise, in part, from the multireference character of this system, as confirmed by the T1 diagnostic and CASSCF calculations.


Dietary sources of N-nitroso compounds and bladder cancer risk: findings from the Los Angeles bladder cancer study.
N-Nitroso compounds (NOCs) have been proposed as possible bladder carcinogens. The main sources of exogenous exposure to NOCs are cigarette smoke and diet, particularly processed (i.e., nitrite-treated) meats. Perhaps more importantly, NOCs can be formed endogenously from dietary precursors such as nitrate, nitrite and amines. Heme has been shown to increase endogenous nitrosation. We examined the role of dietary sources of NOCs and NOC precursors as potential bladder cancer risk factors using data from the Los Angeles Bladder Cancer Study, a population-based case-control study. Dietary and demographic information was collected from 1,660 bladder cancer cases and 1,586 controls via a structured questionnaire. Intake of liver and of salami/pastrami/corned beef, were both statistically significantly associated with risk of bladder cancer in this study, particularly among nonsmokers. Heme intake was also statistically significantly associated with risk of bladder cancer among nonsmokers only. When considering NOC precursors, risk was consistently higher among subjects with concurrent high intake of nitrate and high intake of the different meats (sources of amines and nitrosamines). Results of this study are consistent with a role of dietary sources of NOC precursors from processed meats in bladder cancer risk, suggesting consumption of meats with high amine and heme content such as salami and liver as a risk factor for bladder cancer. In addition, any effect of consuming these meats may be greater when accompanied by high nitrate intake.


The impact of COVID-19 lockdown on professional soccer players' body composition and physical fitness.
During the COVID-19 lockdown, professional soccer players ceased their regular team training sessions and were provided with exercise programs to follow independently. This investigation assessed the impact of a 7-week COVID-19 lockdown and home-based individual physical training on professional soccer players' body composition and physical fitness. The study consisted of nineteen division 1 elite soccer players (age 27.68 ± 5.99 years, height 178.47 ± 5.44 cm) and compared the anthropometric and physical fitness parameters obtained post-transition period to those obtained post-COVID-19 lockdown. The statistical analysis indicated that body fat percentage was significantly higher after the lockdown period [t(18) = -5.59, p < 0.01, d = 0.56]. Furthermore, VO2max [t(17) = -11.54, p < 0.01, d = 0.57] and running time [t(17) = 3.94, p < 0.01, d = 0.76] values were significantly higher after the COVID-19 lockdown than those obtained after the transition period. In addition, significantly higher level of performance was demonstrated on squat jump [t(18) = -4.10, p < 0.01, d = 0.30], countermovement jump [t(18) = -7.43, p < 0.01, d = 1.11] and sit and reach tests [t(19) = -5.33, p < 0.01, d = 0.32]. Concurrently, lower body strength was indicated to be significantly greater (p < 0.01) following the COVID-19 lockdown. The training protocol provided during the confinement, due to the COVID-19 outbreak, was effective in keeping physical fitness at a significantly higher level compared to the transition period. Coaches and trainers are encouraged to examine the effectiveness of this protocol, as it may help them develop effective periodization programs during the transition period. This protocol may aid in the development of effective periodization programs that require minimal equipment and can be followed in similar situations.


Effect of a low dose of midazolam on high blood pressure in dental patients: a randomised, double-blind, placebo-controlled, two-centre study.
Some patients have transient hypertension before dental treatment as a result of anxiety and stress. Midazolam is an anxiolytic, and thought to be effective for the management of this sort of transient hypertension. We have evaluated in a randomised, controlled trial whether a low dose of midazolam can lower blood pressure in dental patients to an acceptable level without excessive sedation. Suitable patients were randomised to be given midazolam (trial group) or physiological saline (control group) intravenously. Blood pressure, heart rate, degree of anxiety, and amount of sedation were measured before and after injection. After injection, blood pressure in the trial group significantly decreased to clinically acceptable levels compared with controls. The degree of anxiety in the trial group was also significantly less than that in the control group, but there were no significant differences in sedation. These results suggest that injection of a low dose of midazolam stabilises the blood pressure of dental patients with transient hypertension.


Timing for starting second-line therapy in recurrent ovarian cancer.
Ovarian cancer is the leading cause of gynecologic cancer-related death in Europe and the USA. The optimal treatment strategy for this malignancy includes accurate presurgical and surgical staging, optimal debulking surgery, and first-line therapy with platinum-based chemotherapy. Unfortunately, the majority of patients diagnosed with advanced ovarian cancer will eventually relapse and die. However, an appropriate management can have a major impact on survival: salvage chemotherapy can prolong survival in the majority of cases and, in selected patients, surgical cytoreduction of recurrent disease can be beneficial. The optimal timing for starting second-line therapy should be based on symptomatic or radiologic recurrence. In fact, even though cancer antigen 125 (CA 125) elevation significantly anticipates a clinical relapse, a randomized trial failed to show a survival advantage for starting second-line therapy on the basis of CA 125 elevation. This is the most solid evidence coming from a randomized trial; however, we must take into account some limitations: in this study the role of secondary cytoreduction was not considered and, at the time of study conduction, more active salvage drugs/regimens were not yet available. In the near future, a better knowledge of ovarian cancer biology, more sensitive diagnostic techniques, more accurate and less invasive surgical procedures along with the availability of new agents will further improve prognosis. In this scenario, the anticipation of salvage therapy will probably play a different role.


Influence of functional electrical stimulation of the hamstrings on knee kinematics in stroke survivors walking with stiff knee gait.
To explore whether functional electrical stimulation of the hamstrings results in improved knee kinematics in chronic stroke survivors walking with a stiff knee gait. Quasi-experimental. Sixteen adult chronic stroke survivors. Survivors received functional electrical stimulation of the hamstrings, 3 times a week for 1 h during a period of 5 weeks. 3D kinematics was calculated before the training period and after 5 weeks of training. Knee kinematics of walking without stimulation before the training period was compared with walking with stimulation after 5 weeks of training. (intervention effect). In addition, knee kinematics of walking without stimulation before the training period was compared with walking without stimulation after the training period (therapeutic effect). The intervention effect showed a significant increase, of mean 8.7° (standard deviation (SD) 8.3, p = 0.001), in peak knee flexion. The therapeutic effect showed a significant increase in peak knee flexion, of mean 3.1° (SD 4.7, p = 0.021) Conclusion: The results of this exploratory study suggest an increase in knee kinematics in swing after functional electrical stimulation of the hamstrings in stroke survivors walking with a stiff knee gait. The largest improvement in peak knee flexion in swing was seen when participants walked with hamstring stimulation. Participants with low neurological impairment responded better to hamstring stimulation, and there are indications that the effect of hamstring stimulation can be predicted during a single session. The effect of functional electrical stimulation is comparable to that of more invasive treatment options, such as botulinum toxin or soft-tissue surgery. This makes functional electrical stimulation a feasible treatment option for daily clinical practice.


Herbivore-specific, density-dependent induction of plant volatiles: honest or "cry wolf" signals?
Plants release volatile chemicals upon attack by herbivorous arthropods. They do so commonly in a dose-dependent manner: the more herbivores, the more volatiles released. The volatiles attract predatory arthropods and the amount determines the probability of predator response. We show that seedlings of a cabbage variety (Brassica oleracea var. capitata, cv Shikidori) also show such a response to the density of cabbage white (Pieris rapae) larvae and attract more (naive) parasitoids (Cotesia glomerata) when there are more herbivores on the plant. However, when attacked by diamondback moth (Plutella xylostella) larvae, seedlings of the same variety (cv Shikidori) release volatiles, the total amount of which is high and constant and thus independent of caterpillar density, and naive parasitoids (Cotesia vestalis) of diamondback moth larvae fail to discriminate herbivore-rich from herbivore-poor plants. In contrast, seedlings of another cabbage variety of B. oleracea (var. acephala: kale) respond in a dose-dependent manner to the density of diamondback moth larvae and attract more parasitoids when there are more herbivores. Assuming these responses of the cabbage cultivars reflect behaviour of at least some genotypes of wild plants, we provide arguments why the behaviour of kale (B. oleracea var acephala) is best interpreted as an honest signaling strategy and that of cabbage cv Shikidori (B. oleracea var capitata) as a "cry wolf" signaling strategy, implying a conflict of interest between the plant and the enemies of its herbivores: the plant profits from being visited by the herbivore's enemies, but the latter would be better off by visiting other plants with more herbivores. If so, evolutionary theory on alarm signaling predicts consequences of major interest to students of plant protection, tritrophic systems and communication alike.


Detecting clonal rearrangement in non-Hodgkin's lymphomas in Taiwan by polymerase chain reaction.
The detection of monoclonal expansions of the immunoglobulin heavy chain (IgH) or the T-cell receptor-gamma (TCRgamma) chain genes is an important supplement for the diagnosis of the non-Hodgkin's lymphomas (NHLs). Detection of monoclonality by polymerase chain reaction (PCR) method has offered an efficient approach for rapid diagnosis and monitoring of the therapeutic effects. Here we conducted a retrospective PCR clonality study on 49 cases of NHLs including 23 B-cell lymphomas (BCLs), 20 peripheral T-cell lymphomas (PTCLs), 6 natural killer (NK)/T-cell lymphomas and 3 reactive lymphoid tissues from southern Taiwan. Genomic DNAs from paraffin sections were extracted and analyzed by the IgH- and TCR-specific PCR reactions. The results showed that 20 of 23 (87.5%) BCLs exhibited IgH gene rearrangements and were all germline for TCRgamma. 15 of 20 (75.0%) PTCLs exhibited TCRgamma gene rearrangements while 1 case (5%) was positive for IgH gene rearrangement. The 6 NK/T-cell lymphomas and 3 reactive lymphoid tissues were all germline for either IgH or TCRgamma genes. Our results were similar to other Western reports in terms of sensitivity and cell-lineage specificity. This is the first large series of PCR clonality study of IgH and TCRgamma gene rearrangements on NHLs from Taiwan. We have confirmed that this rapid method is a sensitive diagnostic tool for NHLs.


Temperature and population density effects on locomotor activity of Musca domestica (Diptera: Muscidae).
The behavior of ectotherm organisms is affected by both abiotic and biotic factors. However, a limited number of studies have investigated the synergistic effects on behavioral traits. This study examined the effect of temperature and density on locomotor activity of Musca domestica (L.). Locomotor activity was measured for both sexes and at four densities (with mixed sexes) during a full light and dark (L:D) cycle at temperatures ranging from 10 to 40°C. Locomotor activity during daytime increased with temperature at all densities until reaching 30°C and then decreased. High-density treatments significantly reduced the locomotor activity per fly, except at 15°C. For both sexes, daytime activity also increased with temperature until reaching 30 and 35°C for males and females, respectively, and thereafter decreased. Furthermore, males showed a significantly higher and more predictable locomotor activity than females. During nighttime, locomotor activity was considerably lower for all treatments. Altogether the results of the current study show that there is a significant interaction of temperature and density on daytime locomotor activity of M. domestica and that houseflies are likely to show significant changes in locomotor activity with change in temperature.


The impact of systolic and diastolic blood pressure variability on mortality is age dependent: Data from the Dublin Outcome Study.
Twenty-four-hour blood pressure variability (BPV) is independently related to cardiovascular outcomes, but limited and conflicting evidence is available on the relative prognostic importance of systolic and diastolic BPV. The aim of this study was to verify the hypothesis that the association of systolic and diastolic blood pressure variability over 24 h with cardiovascular mortality in untreated subjects is affected by age. The study included 9154 untreated individuals assessed for hypertension between 1982 and 2002 in the frame of the Dublin Outcome Study, in which 24 h ambulatory blood pressure monitoring was obtained (age 54.1 ± 14.3 years, 47% males). The association of short-term systolic and diastolic blood pressure variability with cardiovascular and all-cause mortality in the entire sample and separately in younger and older age subgroups was assessed over a median follow-up period of 6.3 years. Diastolic BPV was directly and independently related to cardiovascular mortality (adjusted hazard ratio (adjHR) for daytime standard deviation 1.16 (95% confidence interval 1.08-1.26)) with no significant differences among age groups. Conversely, systolic BPV was independently associated with cardiovascular mortality only in younger (<50 years) subjects (adjHR for daytime standard deviation 1.72 (95% confidence interval 1.33-2.23)), superseding the predictive value of diastolic BPV in this group. Diastolic short-term BPV independently predicts cardiovascular mortality in hypertensive subjects at all ages, while systolic BPV seems a particularly strong predictor in young adults. If confirmed, these findings might improve the understanding of the prognostic value of BPV, with new perspectives for its possible clinical application.


[Attempted suicide: epidemiological changes between 1969-1996. A retrospective study of 1,150 cases].
Over the last 40 years, suicide attempts have become a health problem of epidemic proportions. In order to update preventive measures, we describe the variations observed in the epidemiologic pattern of patients who attempted suicide between 1969-96. A total of 1,150 suicide attempts seen in the Emergency Service of a General Hospital during this period was analyzed. The study protocol included: sociodemographic data, psychiatric antecedents and diagnosis, suicide behaviour and triggering life-events. Throughout the 27 years of the study the most relevant changes in the suicide-attempt population were: progressive levelling between males and females and an increase in antecedents and previous psychiatric treatments (11% vs 74%). The distribution of the psychiatric diagnoses changed in its relative frequency. A dramatic increase was observed in the number of patients who repeated the suicide attempt (22% vs 50%). Triggering life-events tended to vary in relation to sociological changes. Throughout the study period we observed a progressive increase of psychiatric diagnoses in suicidal patients. Therapeutic programs are needed to prevent repetition of suicide attempts, both during periods of psychopathologic exacerbation and during psychosocial adaptation crises triggered by life-events.


Overexpression of mouse follistatin causes reproductive defects in transgenic mice.
Follistatin is an activin-binding protein that can act as an activin antagonist in vitro. Follistatin also binds heparin sulfate proteoglycans and may function as a reservoir for activins in vivo. In the mouse, follistatin mRNA is first detected in the deciduum on embryonic day 5.5 and later in the developing hindbrain, somites, vibrissae, teeth, epidermis, and muscle. We have previously shown that follistatin-deficient mice have numerous embryonic defects including shiny, taut skin, growth retardation, and cleft palate leading to death within hours of birth. To further define the roles of follistatin during mammalian reproduction and development, we created gain-of-function mutant mice in which mouse follistatin is overexpressed. The mouse metallothionein (MT)-I promoter was placed upstream of the six-exon mouse follistatin (FS) gene. To distinguish wild-type and transgenic follistatin mRNA, the 3'-untranslated region of the mouse follistatin gene was replaced with the SV40 untranslated and polyA sequences. Three male and two female founder transgenic mice were produced, were fertile, and transmitted the transgene to offspring. Northern blot analysis demonstrated that the transgene mRNA was expressed at varying levels in the livers of offspring from four of five of the transgenic lines and was expressed in the testes in all five lines. In MT-FS line 4, which had the highest expression of the transgene mRNA in the liver, the transgene transcripts were also present in multiple other tissues. Phenotypically, the MT-FS transgenic lines had defects in the testis, ovary, and hair. Mice from MT-FS lines 7 and 10 had slightly decreased testis size, whereas mice from lines 4, 5, and 9 had much smaller testes and shiny, somewhat irregular, fur. Histological analysis of the adult testes from line 5 and 9 males showed variable degrees of Leydig cell hyperplasia, an arrest of spermatogenesis, and seminiferous tubular degeneration leading to infertility. Female transgenic mice from lines 4 and 9 had thin uteri and small ovaries due to a block in folliculogenesis at various stages. Many of the line 9 female mice eventually became infertile, and all of the line 4 female mice were infertile. Suppressed serum FSH levels were seen in only the line 4 transgenic male and female mice, the line with widespread expression of the transgene. Serum FSH levels were not significantly different in gonadectomized wild-type and line 5 transgenic male mice despite high levels of the follistatin transgene mRNA in the liver of these transgenic mice. These results suggest that follistatin exerts its effects at the levels of the gonads and pituitary as a local regulator of activin and possibly other transforming growth factor-beta family members.


Effect of misfit strain on the buckling of graphene/MoS2van der Waals heterostructures.
Van der Waals heterostructures inherit many novel electronic and optical properties from their constituent atomic layers. Mechanical stability is key for realizing high-performance nanodevices based on van der Waals heterostructures. However, buckling instability is a critical mechanical issue for heterostructures associated with its two-dimensional nature. Using molecular dynamics simulations of graphene/MoS2heterostructures, we demonstrate the relationship between buckling instability and the misfit strain that arises inevitably in such heterostructures. The impact of misfit strain on buckling depends on its magnitude: (1) A negative misfit strain causes a pre-compression of the graphene layer, which in turn initiates and accelerates buckling in this layer and reduces the buckling stability in the heterostructure as a whole. (2) A small positive misfit strain enhances the buckling stability of the graphene/MoS2heterostructure by pre-stretching and hence decelerating the buckling of the graphene layer (where heterostructure buckling is initiated). (3) In the case of a large positive misfit strain, the graphene layer is pre-stretched while the MoS2layer is significantly pre-compressed, so that heterostructure buckling is initiated by the MoS2layer. Consequently, the buckling stability of the graphene/MoS2heterostructure is reduced by increasing the large positive misfit strain. These findings are valuable for understanding the mechanical properties of van der Waals heterostructures.


Synergistic action of nikkomycin X/Z with azole antifungals on Candida albicans.
Fluconazole, ketoconazole and tioconazole were shown to act synergistically in vitro with the antibiotic nikkomycin X/Z on the pathogenic fungus Candida albicans. The phenomenon was demonstrated using a checkerboard technique and growth inhibition experiments. The azole antifungal agents, even at concentrations not affecting growth, decreased the incorporation of the 14C-label from [14C]glucose into chitin of the candidal cell wall. After 3 h incubation with tioconazole, 1 microgram ml-1, the incorporation of the radiolabelled glucose into chitin of intact cells and regenerating spheroplasts of C. albicans was inhibited by 43% and 30%, respectively. Moreover, the relative chitin content was approximately 45% lower than that of control cells. The chitin content increased after prolonged incubation with azoles, thus confirming the known phenomenon of azole-induced uncoordinated chitin synthesis and deposition. On the other hand, azole derivatives had very little effect on the rate of nikkomycin transport into C. albicans cells. A sequential blockade mechanism of synergism is proposed.


Assessment of Online Resources for Returning to School During and After Treatment of Childhood Cancer.
To evaluate current online parent education resources for children returning to school after a cancer diagnosis. Online search was conducted using 3 search engines and terms recommended by affected families. Sites were evaluated by 3 reviewers for understandability and actionability (scored 0-100%) using the Patient Education Materials Assessment Tool (PEMAT). Readability was assessed using Flesch-Kincaid (grade K-12) and content comprehensiveness by a clinical expert review for 5 late effect domains (scored 0-100%). A total of 56 unique online resources were evaluated. Mean understandability and actionability scores were 54% (range 17-83) and 36% (range 0-83) respectively. The mean Flesch-Kincaid grade level was 10th grade (mode 12th). Comprehensiveness of domain coverage was 34% (mode 20%). Some high-quality materials for this topic are available, but generally low scores on the PEMAT scales and high reading level estimates on Flesch-Kincaid indicate parents may have difficulty understanding and using the information. The low scores for comprehensiveness of information indicate parents will likely need to access multiple sources for complete information. A table provides the names, website (URL), and scoring for the 24 top-rated sites and can be used to make recommendations to parents with improved confidence in quality.


[The 3D printed drilling template for bilateral sagittal osteotomy].
The bilateral sagittal osteotomy (BSSO) is a widely used surgical technique within orthognatic surgery. The specific osteotomy design may vary from clinic to clinic. The best position of the bone cuts in a BSSO continues to be a point of discussion and probably differs from patient to patient. In addition, standardisation in, for example, research may be desirable. Pre-operative planning using a drilling template in order to position the planned individual saw cuts during BSSO can be of value. To achieve this goal, a pre-operative 3D printed biocompatible drilling template was manufactured for 1 patient on the basis of pre-operative planning. The difference between the pre-operatively determined bone cuts with the assistance of the drilling template and the actual bone cuts was still large.


Clinical significance of serum transforming growth factor-beta 1 (TGF-β1) levels in patients with epithelial ovarian cancer.
Transforming growth factor-beta 1 (TGF-β1) plays an important role in the pathogenesis of multiple malignancies, and its expression also strongly affects the outcomes of cancer patients. The objective of this study was to determine the clinical significance of the serum levels of TGF-β1 in epithelial ovarian cancer (EOC) patients. A total of 50 patients with a pathologically confirmed diagnosis of EOC were enrolled into this study. Serum TGF-β1 concentrations were determined by the solid-phase sandwich ELISA method. Thirty age- and sex-matched healthy controls were included in the analysis. Median age of patients was 56.5 years old (range 22 to 83 years). Majority of the patients had advanced disease (FIGO stage III-IV; 90%). There was no significant difference in baseline serum TGF-β1 levels between EOC patients and the controls (p = 0.39). A trend to significant relationship was found between the serum levels of TGF-β1 and stage of disease (p = 0.06). The elevated serum TGF-β1 level was associated with metastatic disease. The other known clinical variables including histology, grade of histology, debulking surgery, and serum CA 125 levels were not found to be correlated with serum TGF-β1 concentrations (p > 0.05). Only the chemotherapy-unresponsive patients had higher serum TGF-β1 levels compared with responsive ones (p = 0.02). Serum TGF-β1 concentration was found to have no prognostic role for both progression-free and overall survivals (p = 0.42 and p = 0.09, respectively). In conclusion, although the serum level of TGF-β1 has no diagnostic and prognostic role, it is associated with sensitivity to standard chemotherapy in EOC patients.


Intranasal oxytocin as an adjunct treatment among patients with severe major depression with and without comorbid borderline personality disorder.
Results of studies concerning a possible beneficial effect of Intranasal-Oxytocin (IN-OT) as an add-on treatment for patients with major depression (MDD) have been inconsistent. One possible explanation to account for the difference in the effect of IN-OT is comorbid borderline personality disorder (BPD). This randomized controlled study was aimed to explore the differential effect of IN-OT administration among depressive patients with or without comorbid borderline personality disorder. A secondary analysis was conducted on a specific subset of patients who participated in an RCT evaluating the impact of IN-OT as add-on treatment for patients with severe mental illness. Patients treated in inpatient settings (N = 58) were randomized and double-blindly allocated to receive twice daily IN-OT (32 IU) or placebo for a period of four weeks. The effect of IN-OT on therapy process and outcome was examined among patients with (n = 35) and without (n = 23) comorbid BPD. An interaction effect between diagnosis and group was observed on the Outcome Questionnaire-45 (B = 8.93, p = .007). Further analysis revealed that patients without BPD demonstrated significantly greater improvements following OT administration (B = -8.32, p = .001), whereas patients with BPD did not show significant improvement (B = 0.61, p = .76). The interactive pattern was also observed in the Hopkins Symptom Checklist (B = 0.25, p = .02), where patients without BPD demonstrated significantly larger improvements following OT administration (B = -0.29, p = .0009) as compared to placebo, while patients with BPD demonstrated no significant improvement (B = -0.04, p = .55). We did not find a harmful effect of IN-OT administration among patients with MDD and comorbid BPD. Patients with MDD and comorbid BPD benefit less from IN-OT administration as compared to depressed patients without BPD. Future studies should aim to identify patients who are more likely to benefit from IN-OT administration.


Seabed gallery intakes: Investigation of the water pretreatment effectiveness of the active layer using a long-term column experiment.
Seabed gallery intake systems used for seawater reverse osmosis facilities employ the same principle of water treatment as slow sand filtration in freshwater systems. An investigation concerning the effectiveness of the active layer (top layer) in improving raw water quality was conducted by using a long-term bench-scale columns experiment. Two different media types, silica and carbonate sand, were tested in 1 m columns to evaluate the effectiveness of media type in terms of algae, bacteria, Natural Organic Matter (NOM) and Transparent Exopolymer Particles (TEP) removal over a period of 620 days. Nearly all algae in the silica sand column, 87% (σ = 0.04) of the bacteria, 59% (σ = 0.11) of the biopolymer fraction of NOM, 59% (σ = 0.16) of particulate and 32% (σ = 0.25) of colloidal TEP were removed during the last 330 days of the experiment. Total removal was observed in the carbonate sand column for algal concentration, while the bacterial removal was lower at 74% (σ = 0.08). Removal of biopolymers, particulate and colloidal TEP were higher in the carbonate column during the last 330 days with 72% (σ = 0.15), 66% (σ = 0.08) and 36% (σ = 0.12) removed for these organics respectively. Removal of these key organics through the 1 m thick column, representing the active layer, will likely reduce the rate of biofouling, reduce chemical usage and minimize operating cost in SWRO systems. The data show that the media will require several months at the beginning of operation to reach equilibrium so that high organic removal rates can be achieved. No development of a "schmutzdecke" layer occurred. The experimental results suggest that unlike freshwater slow sand filtration wherein most water treatment occurs in the upper 10 cm, in seawater systems treatment occurs throughout the full active layer depth of 1 m. The results of this study will help in designing and operating seabed gallery intake systems in varied geological conditions.


Aquatic Exercises in the Treatment of Low Back Pain: A Systematic Review of the Literature and Meta-Analysis of Eight Studies.
Low back pain is the most common musculoskeletal condition with a high prevalence. There was no sufficient evidence to recommend that aquatic exercise was potentially beneficial to patients with low back pain. The aim of this study was to systematically analyze all evidence available in the literature about effectiveness of the aquatic exercise. A comprehensive search of PubMed, the Cochrane Library, Embase, and Cumulative Index to Nursing and Allied Health was conducted from their inceptions to November 2016 for randomized controlled trials, which concerned the therapeutic aquatic exercise for low back pain. The results were expressed in terms of standardized mean difference and the corresponding 95% confidence interval. Eight trials involving 331 patients were included in the meta-analysis, and the results showed a relief of pain (standardized mean difference = -0.65, 95% confidence interval = -1.16 to -0.14) and physical function (standardized mean difference = 0.63, 95% confidence interval = 0.17 to 1.09) after aquatic exercise. However, there was no significant effectiveness with regard to general mental health in aquatic group (standardized mean difference = 0.46; 95% confidence interval = -0.22 to 1.15). Aquatic exercise can statistically significantly reduce pain and increase physical function in patients with low back pain. Further high-quality investigations on a larger scale are required to confirm the results.