Polymer-Based Nanomaterials for Photothermal Therapy: From Light-Responsive to Multifunctional Nanoplatforms for Synergistically Combined Technologies.
Materials for the treatment of cancer have been studied comprehensively over the past few decades. Among the various kinds of biomaterials, polymer-based nanomaterials represent one of the most interesting research directions in nanomedicine because their controlled synthesis and tailored designs make it possible to obtain nanostructures with biomimetic features and outstanding biocompatibility. Understanding the chemical and physical mechanisms behind the cascading stimuli-responsiveness of smart polymers is fundamental for the design of multifunctional nanomaterials to be used as photothermal agents for targeted polytherapy. In this review, we offer an in-depth overview of the recent advances in polymer nanomaterials for photothermal therapy, describing the features of three different types of polymer-based nanomaterials. In each case, we systematically show the relevant benefits, highlighting the strategies for developing light-controlled multifunctional nanoplatforms that are responsive in a cascade manner and addressing the open issues by means of an inclusive state-of-the-art review. Moreover, we face further challenges and provide new perspectives for future strategies for developing novel polymeric nanomaterials for photothermally assisted therapies.


Stereotactic Ablative Body Radiation for Stage I Lung Cancer in Israel: A Retrospective Single-Center Report.
Stereotactic ablative radiation therapy (SABR) is the application of a very high radiation dose to a small treatment volume. It is the new standard of care in medically inoperable early-stage lung cancer. To report the outcomes of SABR in stage I lung cancer at Sheba Medical Center since its introduction in 2009. We conducted a retrospective chart review of patients with stage I lung cancer treated during the period 2009-2015. Survival status was retrieved from the electronic medical records and confirmed with the national registry. Local failure was defined as increased FDG uptake on PETCT scan within a 2 cm radius of the treated region. Toxicity was estimated from medical records and graded according to common toxicity criteria for adverse events (CTCAE) version 4.03. Overall survival and local control were estimated by the Kaplan-Meier method. During the study period 114 patients were treated for 122 stage I lung cancer lesions. Median follow-up time was 27 months (range 8.2-69.5 months), median age was 76 years. Eighty-two percent of the tumors were stage IA (size ≤ 3 cm). Median survival was 46 months; estimated 3 year overall survival was 59% (95%CI 47-69%) and local control was 88% (95%CI 78-94%). Toxicity included chest wall pain in 8.4% of patients, rib fracture in 0.9%, grade 1-2 pneumonitis in 12%, grade 3 in 12% and grade 5 (death) in 0.9%. SABR has been successfully implemented at Sheba Medical Center for the treatment of stage I lung cancer in inoperable patients. It is associated with excellent local control, minor toxicity and an acceptable overall survival.


Morphometric profile of tendocalcaneus of South Africans of European ancestry using a cadaveric approach.
Tendocalcaneus is a strong tendon that is vital for bipedalism in humans. Despite its tremendous strength, the tendocalcaneus is prone to damage and degeneration causing mobility problems and pain. Morphometric dimension of the tendocalcaneus is of benefit to the surgical repair and reconstruction of the damaged tendon. Cadaveric approach provides a realistic method for determining tendocalcaneus morphometry and as at present only two cadaveric studies on Indian population is available. Thus this study presents data on tendocalcaneus morphometry in South Africans of European ancestry using a cadaveric approach. A total of 66 lower limbs (32 left and 34 right legs) sourced from 49 male and female cadavers were used. After careful dissection of the posterior aspect of leg, the medial and lateral length, distal width, distal circumference and proximal width of the tendocalcaneus were measured. The data showed a high degree of reproducibility indicating that the measurements obtained using cadaveric approach were precise and accurate. There was no difference in measurements between the sides. Measurements in the males were generally higher than in the females. Strong associations were observed between the paired measurements of the medial and lateral tendon length and between the distal width and distal circumference. The data obtained will be useful in predicting tendocalcaneus size during the surgical reconstruction of the tendocalcaneus.


Proceedings from the Ice Hockey Summit III: Action on Concussion.
The Ice Hockey Summit III provided updated scientific evidence on concussions in hockey to inform these five objectives: 1) describe sport-related concussion (SRC) epidemiology, 2) classify prevention strategies, 3) define objective, diagnostic tests, 4) identify treatment, and 5) integrate science and clinical care into prioritized action plans and policy. Our action plan evolved from 40 scientific presentations. The 155 attendees (physicians, athletic trainers, physical therapists, nurses, neuropsychologists, scientists, engineers, coaches, and officials) voted to prioritize these action items in the final Summit session. 1) Establish a national and international hockey data base for SRC at all levels, 2) eliminate body checking in Bantam youth hockey games, 3) expand a behavior modification program (Fair Play) to all youth hockey levels, 4) enforce game ejection penalties for fighting in Junior A and professional hockey leagues, 5) establish objective tests to diagnose concussion at point of care (POC), and 6) mandate baseline testing to improve concussion diagnosis for all age groups. Expedient implementation of the Summit III prioritized action items is necessary to reduce the risk, severity, and consequences of concussion in the sport of ice hockey.


Renal Autotransplantation in Metachronous Solitary Contralateral Ureteral Metastasis from Renal Cell Carcinoma: A Case Report.
Ureteral metastasis of renal cell carcinoma (RCC) is rare and usually confined to the ipsilateral ureter. In literature, about 50 cases have been reported so far. Of these, only 14 metastasized metachronously to the contralateral ureter.A seventy-one-year-old man was hospitalized with recurrent painless severe haematuria. Seven years previously, he had undergone radical nephrectomy of the right kidney due to a clearcell renal cell carcinoma (cRCC), Fuhrman grad 2. Intravenous urography and a retrograde ureterogram revealed a filling defect (25 mm) in the left distal ureter, which we expected to be an urothelial carcinoma. Biopsy was not possible, due to ureteral stricture. Diagnostic workup revealed no other sites of metastasis. To preserve kidney function and quality of life we refrainedfrom performing nephroureterectomy and opted for an autotransplantation of the solitary left kidney with ureteral reimplantation in the bladder. We resected the ureter and histopathologicial examination showed a metastasis of cRCC, Fuhrman grade 2.Postoperatively, the patient developed an acute postrenal failure, hence a nephrostomy and a bladder catherization were performed. After this, the patient improved significantly and the drains could be removed. Currently the patient is free of complaints. The residual and contralateral ureter is a potential metastatic site after RCC. Autotransplantation is an option forsurgical treatment.


Chitinolytic activity of Pseudomonas fluorescens isolates from barley and sugar beet rhizosphere.
Twelve isolates of Pseudomonas fluorescens, isolated from barley and sugar beet rhizosphere as antagonists towards the plant pathogenic microfungi Rhizoctonia solani and Pythium ultimum, showed chitinolytic activity in batch cultures when grown in media without exogenous chitin. Enzyme tests in cultures demonstrated a complete array of chitinolytic enzymes. Endochitinase and chitobiosidase activities seemed to be tightly coupled in the isolates, while there was no relationship to N-acetyl-glucosaminidase activity. Endochitinase activity, showing hydrolysis of chitin polymers, was found to be extracellular in all isolates, although the most active isolates also retained a cell-bound fraction. Isoelectric focusing gel electrophoresis of supernatants containing extracellular enzyme activity showed that all isolates produced one native endochitinase in logarithmic phase. This enzyme was subsequently modified into several isozymes by extracellular processing as the cultures aged in stationary phase. The 12 isolates could be grouped into seven isozymic patterns. Detailed studies of three selected isolates showed that extracellular release of endochitinase activity also took place in stationary phase. The results, however, indicated that in stationary phase regulation of both the overall production of native enzyme and the subsequent formation of isozymes were different among the P. fluorescens isolates.


A Smartphone App for Supporting the Self-management of Daytime Urinary Incontinence in Adolescents: Development and Formative Evaluation Study of URApp.
Daytime urinary incontinence (UI) is common in childhood and often persists into adolescence. UI in adolescence is associated with a range of adverse outcomes, including depressive symptoms, peer victimization, poor self-image, and problems with peer relationships. The first-line conservative treatment for UI is bladder training (standard urotherapy) that aims to establish a regular fluid intake and a timed schedule for toilet visits. The success of bladder training is strongly dependent on good concordance, which can be challenging for young people. This paper aims to describe the development of a smartphone app (URApp) that aims to improve concordance with bladder training in young people aged 11 to 19 years. URApp was designed by using participatory co-design methods and was guided by the person-based approach to intervention design. The core app functions were based on clinical guidance and included setting a daily drinking goal that records fluid intake and toilet visits, setting reminders to drink fluids and go to the toilet, and recording progress toward drinking goals. The development of URApp comprised the following four stages: a review of current smartphone apps for UI, participatory co-design workshops with young people with UI for gathering user requirements and developing wireframes, the development of a URApp prototype, and the user testing of the prototype through qualitative interviews with 23 young people with UI or urgency aged 10 to 19 years and 8 clinicians. The app functions and additional functionalities for supporting concordance and behavior change were iteratively optimized throughout the app development process. Young people who tested URApp judged it to be a helpful way of supporting their concordance with a timed schedule for toilet visits and drinking. They reported high levels of acceptability and engagement. Preliminary findings indicated that some young people experienced improvements in their bladder symptoms, including a reduction in UI. Clinicians reported that URApp was clinically appropriate and aligned with the best practice guidelines for bladder training. URApp was deemed age appropriate, with all clinicians reporting that they would use it within their own clinics. Clinicians felt URApp would be of particular benefit to patients whose symptoms were not improving or those who were not engaging with their treatment plans. The next stage is to evaluate URApp in a range of settings, including pediatric continence clinics, primary care, and schools. This research is needed to test whether URApp is an effective (and cost-effective) solution for improving concordance with bladder training, reducing bladder symptoms, and improving the quality of life.


Racial disparities in the use of voice preservation therapy for locally advanced laryngeal cancer.
To identify potential racial disparities in the use of larynx preservation. Retrospective database review. Academic medical center. The Surveillance Epidemiology and End Results (SEER) database was used to identify white, black, Hispanic, and Asian patients with stage III and IV laryngeal cancers that were diagnosed during 1991 through 2008. Patients with T4 disease or distant metastasis were intentionally excluded. Univariate and multivariate logistic regression analysis, with odds ratios and 95% confidence intervals, was used to investigate the relationship between race/ethnicity and the use of larynx preservation with radiation therapy as initial therapy. Among the 5385 cases of laryngeal cancers that met the selection criteria, the racial distribution was white (72.7%), black (16.8%), Hispanic (7.4%), and Asian (3.1%). On univariate analysis, blacks (odds ratio [OR], 0.72; 95% CI, 0.59-0.88) were significantly less likely to undergo larynx preservation. This racial disparity persisted on multivariate analysis for blacks (OR, 0.78; 95% CI, 0.63-0.96) and was still observed among patients treated more recently between 2001 and 2008 (OR, 0.74; 95% CI, 0.56-0.96). Pronounced racial disparities exist in the use of larynx preservation therapy for locally advanced laryngeal cancer. While acknowledging the potential biases of socioeconomic factors, further research to better elucidate the underlying reasons for these findings may be warranted.


Identifying and improving the "ground truth" of race in disparities research through improved EMR data reporting. A systematic review.
Studies about racial disparities in healthcare are increasing in quantity; however, they are subject to vast differences in definition, classification, and utilization of race/ethnicity data. Improved standardization of this information can strengthen conclusions drawn from studies using such data. The objective of this study is to examine how data related to race/ethnicity are recorded in research through examining articles on race/ethnicity health disparities and examine problems and solutions in data reporting that may impact overall data quality. In this systematic review, Business Source Complete, Embase.com, IEEE Xplore, PubMed, Scopus and Web of Science Core Collection were searched for relevant articles published from 2000 to 2020. Search terms related to the concepts of electronic medical records, race/ethnicity, and data entry related to race/ethnicity were used. Exclusion criteria included articles not in the English language and those describing pediatric populations. Data were extracted from published articles. This review was organized and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement for systematic reviews. In this systematic review, 109 full text articles were reviewed. Weaknesses and possible solutions have been discussed in current literature, with the predominant problem and solution as follows: the electronic medical record (EMR) is vulnerable to inaccuracies and incompleteness in the methods that research staff collect this data; however, improved standardization of the collection and use of race data in patient care may help alleviate these inaccuracies. Conclusions drawn from large datasets concerning peoples of certain race/ethnic groups should be made cautiously, and a careful review of the methodology of each publication should be considered prior to implementation in patient care.


Outcomes of Noninvasive and Invasive Ventilation in Patients Hospitalized with Asthma Exacerbation.
Little is known about the effectiveness of noninvasive ventilation for patients hospitalized with asthma exacerbation. To assess clinical outcomes of noninvasive (NIV) and invasive mechanical ventilation (IMV) and examine predictors for NIV use in patients hospitalized with asthma. This was a retrospective cohort study at 97 U.S. hospitals using an electronic medical record database. We developed a hierarchical regression model to identify factors associated with the choice of initial ventilation and used the Laboratory Acute Physiological Score to adjust for differences in the severity of illness. We assessed the outcomes of patients treated with initial NIV or IMV in a propensity-matched cohort. Among 13,930 subjects, 73% were women and 54% were white. The median age was 53 years. Overall, 1,254 patients (9%) required ventilatory support (NIV or IMV). NIV was the initial ventilation method for 556 patients (4.0%) and IMV for 668 (5.0%). Twenty-six patients (4.7% of patients treated with NIV) had to be intubated (NIV failure). The in-hospital mortality was 0.2, 2.3, 14.5, and 15.4%, and the median length of stay was 2.9, 4.1, 6.7, and 10.9 days among those not ventilated, ventilated with NIV, ventilated with IMV, and with NIV failure, respectively. Older patients were more likely to receive NIV (odds ratio, 1.06 per 5 yr; 95% confidence interval [CI], 1.01-1.11), whereas those with higher acuity (Laboratory Acute Physiological Score per 5 units: odds ratio, 0.85; 95% CI, 0.82-0.88) and those with concomitant pneumonia were less likely to receive NIV. In a propensity-matched sample, NIV was associated with a lower inpatient risk of dying (risk ratio, 0.12; 95% CI, 0.03-0.51) and shorter lengths of stay (4.3 d less; 95% CI, 2.9-5.8) than IMV. Among patients hospitalized with asthma exacerbation and requiring ventilatory support (NIV or IMV), more than 40% received NIV. Although patients successfully treated with NIV appear to have better outcomes than those treated with IMV, the low rate of NIV failure suggests that NIV was being used selectively in a lower risk group. The increased risk of mortality for patients who fail NIV highlights the need for careful monitoring to avoid possible delay in intubation.


Stabilization of oil-in-water emulsions by colloidal particles modified with short amphiphiles.
Emulsions stabilized through the adsorption of colloidal particles at the liquid-liquid interface have long been used and investigated in a number of different applications. The interfacial adsorption of particles can be induced by adjusting the particle wetting behavior in the liquid media. Here, we report a new approach to prepare stable oil-in-water emulsions by tailoring the wetting behavior of colloidal particles in water using short amphiphilic molecules. We illustrate the method using hydrophilic metal oxide particles initially dispersed in the aqueous phase. The wettability of such particles in water is reduced by an in situ surface hydrophobization that induces particle adsorption at oil-water interfaces. We evaluate the conditions required for particle adsorption at the liquid-liquid interface and discuss the effect of the emulsion initial composition on the final microstructure of oil-water mixtures containing high concentrations of alumina particles modified with short carboxylic acids. This new approach for emulsion preparation can be easily applied to a variety of other metal oxide particles.


A new promising treatment in systemic sclerosis: 5-fluorouracil.
Twelve patients with systemic sclerosis according to American Rheumatism Association criteria were treated with intravenous 5-fluorouracil. Significant subjective and objective improvement occurred initially in the skin and subsequently in the involved viscera and vasculature. These preliminary results suggest that 5-fluorouracil may be an effective treatment for systemic sclerosis.


Health Status and Chronic Disease Burden of the Homeless Population: An Analysis of Two Decades of Multi-Institutional Electronic Medical Records.
Using a multi-institutional EMR registry, we extracted housing status and evaluated the presence of several important comorbidities in order to describe the demographics and comorbidity burden of persons experiencing homelessness in northeast Ohio and compare this to non-homeless individuals of varying socioeconomic position. Of 1,974,766 patients in the EMR registry, we identified 15,920 (0.8%) as homeless, 351,279 (17.8%) as non-homeless and in the top quintile of area deprivation index (ADI), and 1,607,567 (81.4%) as non-homeless and in the lower four quintiles of area deprivation. The comorbidity burden was highest in the homeless population with depression (48.1%), anxiety (45.8%), hypertension (44.2%), cardiovascular disease (18.4%), and hepatitis (18.1%) among the most prevalent conditions. We conclude that it is possible to identify homeless individuals and document their comorbidity burden using a multi-institutional EMR registry, in order to guide future interventions to address the health of the homeless at the health-system and community level.


US air pollution is associated with increased incidence of non-syndromic cleft lip/palate.
Maternal cigarette use is associated with the fetal development of orofacial clefts. Air pollution should be investigated for similar causation. We hypothesize that the incidence of non-syndromic cleft lip with or without palate (NSCLP) and non-syndromic cleft palate (NSCP) would be positively correlated with air pollution concentration. The incidence of NSCLP and NSCP per 1000 live births from 2016 to 2020 was extracted from the Centers for Disease Control and Prevention Vital Statistics Database and merged with national reports on air pollution using the Environmental Protection Agency Air Quality Systems annual data. The most commonly reported pollutants were analyzed including benzene, sulfur dioxide (SO2), particulate matter (PM) 2.5, PM 10, ozone (O3), and carbon monoxide (CO). Multivariable negative binomial and Poisson log-linear regression models evaluated the incidence of NSCLP and NSCP as a function of the pollutants, adjusting for race. All p-values are reported with Bonferroni correction. The median NSCLP incidence was 0.22/1000 births, and isolated NSCP incidence was 0.18/1000 births. For NSCLP, SO2 had a coefficient estimate (CE) of 0.60 (95% CI [0.23, 0.98], p < 0.007) and PM 2.5 had a CE of 0.20 (95% CI [0.10, 0.31], p < 0.005). Among isolated NSCP, no pollutants were found to be significantly associated. SO2 and PM 2.5 were significantly correlated with increased incidence of NSCLP. The American people and perinatal practitioners should be aware of the connection to allow for risk reduction and in utero screening.


Work, life, and the gender effect: Perspectives of ACVIM Diplomates in 2017. Part 2-The intersection of personal life and professional career.
In the field of veterinary surgery, women neither marry nor have children at the same rate as men, and those who do may experience more career disruption as a result. The American College of Veterinary Internal Medicine (ACVIM) is 1 of the few areas of specialized medicine that is predominantly female; it is unknown if such a demographic shift would produce a different environment for individuals cultivating their personal life. To report data regarding subjective and objective aspects of the intersection of the personal and professional lives of Diplomates of the ACVIM. Eight hundred ninety-six surveys (781 completed) of ACVIM Diplomates, including cardiology, large and small animal internal medicine, neurology, and oncology. An 82-item online survey was distributed to ACVIM Diplomates via Diplomate college listservs. Participation was voluntary. Men were more likely to be married and have children than were women. Women had or adopted their first child at a later career stage compared with men, and agreed more strongly that career stage was an influential factor in family planning. Those with children worked fewer hours compared with those without, and this effect was greater among women. Women were more likely to require external childcare, but most men and women shared childcare responsibilities equally outside of working hours. The intersection of personal and professional life differs between men and women in the ACVIM, which may create different needs, preferences, or barriers to work-life balance in the workforce.


Multicenter Study of the Real-World Use of Ceftaroline versus Vancomycin for Acute Bacterial Skin and Skin Structure Infections.
The objective of this study was to determine if real-world ceftaroline treatment in adults hospitalized for acute bacterial skin and skin structure infections (ABSSSI) is associated with decreased infection-related length of stay (LOSinf) compared to that with vancomycin. This was a retrospective, multicenter, cohort study from 2012 to 2017. Cox proportional hazard regression, propensity score matching, and inverse probability of treatment weighting (IPTW) were used to determine the independent effect of treatment group on LOSinf The patients were adults hospitalized with ABSSSI and treated with ceftaroline or vancomycin for ≥72 h within 120 h of diagnosis at four academic medical centers and two community hospitals in Arizona, Florida, Michigan, and West Virginia. A total of 724 patients were included (325 ceftaroline treated and 399 vancomycin treated). In general, ceftaroline-treated patients had characteristics consistent with a higher risk of poor outcomes. The unadjusted median LOSinf values were 5 (interquartile range [IQR], 3 to 7) days and 6 (IQR, 4 to 8) days in the vancomycin and ceftaroline groups, respectively (hazard ratio [HR], 0.866; 95% confidence interval [CI], 0.747 to 1.002). The Cox proportional hazard model (adjusted HR [aHR], 0.891; 95% CI, 0.748 to 1.060), propensity score-matched (aHR, 0.955; 95% CI, 0.786 to 1.159), and IPTW (aHR, 0.918; 95% CI, 0.793 to 1.063) analyses demonstrated no significant difference in LOSinf between groups. Patients treated with ceftaroline were significantly more likely to meet criteria for discharge readiness at day 3 in unadjusted and adjusted analyses. Although discharge readiness at day 3 was higher in ceftaroline-treated patients, LOSinf values were similar between treatment groups. Clinical and nonclinical factors were associated with LOSinf.


Dietary manipulation of cardiac and aortic smooth muscle reactivity to isoproterenol.
The responsiveness to isoproterenol of isolated atria and aortic strips was examined in two groups of male Fischer 344 rats. Group A (control) was composed of 5-mo-old rats fed ad libitum; group R (experimental) was composed of rats whose food intake had been restricted for 2 mo to 60% of that consumed by group A. Aortic strips obtained from group R and preconstricted with 30 mM K+ relaxed by 18% when challenged by a maximal concentration of isoproterenol (1 microM). This relaxation was significantly less than the 28% relaxation observed with strips from group A. No effect on the inotropic response of the left atria or on the chronotropic response of the right atria to maximal concentrations of isoproterenol was observed. A slight but statistically significant increase in sensitivity to isoproterenol was observed in the inotropic response of the left atria. The 50% effective concentration (EC50) for the isoproterenol-stimulated increase in force development observed with group R was 0.87 +/- 0.16 X 10(-8) M, which was significantly less than the value of 1.56 +/- 0.28 X 10(-8) M obtained with atria from group A. Food restriction exerted no significant effect on the EC50 for the chronotropic response of right atria to isoproterenol. Both the body weight and the heart weight of group A were greater than those of group R. However, the ratio of heart weight to body weight was significantly greater in group R than in group A.(ABSTRACT TRUNCATED AT 250 WORDS)


A sensitive and high throughput bacterial luminescence assay for assessing aquatic toxicity--the BLT-Screen.
Bioassays using naturally luminescent bacteria are commonly used to assess the toxicity of environmental contaminants, detected by a decrease in luminescence. Typically, this has involved the use of commercial test kits such as Microtox and ToxScreen. These commercial assays, however, have limitations for routine environmental monitoring, including the need for specialized equipment, a low throughput and high on-going costs. There is therefore a need to develop a bacteria bioassay that is sensitive, high-throughput and cost effective. This study presents the development and application of the BLT-Screen (Bacterial Luminescence Toxicity Screen), a 96-well plate bioassay using Photobacterium leiognathi. During development of the method, the concentration of the phosphate buffer in the experimental medium was adjusted to maximize the sensitivity of the assay, and protocols for analyzing both solid-phase extracts and raw water samples were established. A range of organic compounds and metals were analyzed in the assay, as well as extracts of various water samples, including drinking water, wastewater effluent and river water. The IC50 values of the organic compounds and metals tested in the BLT-Screen were comparable to previously published ToxScreen and Microtox data. In addition, the assay was sensitive enough to detect toxicity in all water types tested, and performed equally well for both solid-phase extracts and raw water samples. The BLT-Screen therefore presents a cost-effective, sensitive and high throughput method for testing the toxicity of environmental contaminants in a range of water types that has widespread applications for research, as well as for routine monitoring and operation of wastewater and drinking water plants.


Processing of radical prostatectomy specimens for correlation of data from histopathological, molecular biological, and radiological studies: a new whole organ technique.
To develop a method of processing non-formalin fixed prostate specimens removed at radical prostatectomy to obtain fresh tissue for research and for correlating diagnostic and molecular results with preoperative imaging. The method involves a prostate slicing apparatus comprising a tissue slicer with a series of juxtaposed planar stainless steel blades linked to a support, and a cradle adapted to grip the tissue sample and receive the blades. The fresh prostate gland is held in the cradle and the blades are moved through the cradle slits to produce multiple 4 mm slices of the gland in a plane perpendicular to its posterior surface. One of the resulting slices is preserved in RNAlater. The areas comprising tumour and normal glands within this preserved slice can be identified by matching it to the haematoxylin and eosin stained sections of the adjacent slices that are formalin fixed and paraffin wax embedded. Intact RNA can be extracted from the identified tumour and normal glands within the RNAlater preserved slice. Preoperative imaging studies are acquired with the angulation of axial images chosen to be similar to the slicing axis, such that stained sections from the formalin fixed, paraffin wax embedded slices match their counterparts on imaging. A novel method of sampling fresh prostate removed at radical prostatectomy that allows tissue samples to be used both for diagnosis and molecular analysis is described. This method also allows the integration of preoperative imaging data with histopathological and molecular data obtained from the prostate tissue slices.


Staffing for Quality in Canadian Long-Term Care Homes.
A coherent workforce strategy and consensus on essential staffing requirements are needed to ensure quality in long-term care (LTC) homes. We have neither in Canada. No Canadian studies, investigator driven or commissioned, exist to guide us. We generally rely on 20-year-old US recommendations, although we have never actually implemented them. During, and in the wake of the COVID-19 pandemic, it is clear that an insufficient workforce was at the root of much of the failure in LTC to manage the pandemic. This commentary frames research on staffing and LTC homes and the impact of COVID-19. It then outlines key ingredients, such as knowledge of residents, the workforce and the care environment, that are needed in order to estimate staffing needs. Recommendations for decision makers are provided.


Analysis of factors contributing to postoperative spinal instability after lumbar decompression for spinal stenosis.
Decompressive laminectomy is one of the most commonly used surgical methods for the treatment of spinal stenosis. We retrospectively examined the risk factors that induce spinal instability, including slippage (spondylolisthesis) and/or segmental angulation after decompressive laminectomy on the lumbar spine. From January 1, 2006 to June 30, 2010, 94 consecutive patients underwent first-time single level decompressive laminectomy without fusion and discectomy. Of these 94 patients, 42 with a follow-up period of at least 2 years were selected. We measured the segmental angulation and slippage in flexion and extension dynamic lumbar radiographs. We analyzed the following contributing factors to spinal instability: age/sex, smoking history, disc space narrowing, body mass index (kg/m(2)), facet joint tropism, effect of the lordotic angle on lumbar spine, asymmetrical paraspinal muscle volume, and surgical method and level. Female patients, normal lordotic angle, and asymmetrical paraspinal muscle volume were factors more significantly associated with spondylolisthesis (p-value=0.026, 0.015, <0.01). Statistical results indicated that patients with facet tropism were more likely to have segmental angulation (p-value=0.046). Facet tropism and asymmetry of paraspinal muscle volume were predisposing factors to spinal instability (p-value=0.012, <0.01). Facet joint tropism and asymmetry of paraspinal muscle volume are the most important factors associated with spinal instability; therefore, careful follow-up after decompressive laminectomy in affected patients is necessary.


Metallurgical approach to enhance the electrochemical activity of magnesium anodes for magnesium rechargeable batteries.
A novel metallurgical approach was adopted to enhance the electrochemical activity of Mg anodes for magnesium rechargeable batteries. The primary electrochemical processes were considered to be grain boundary-mediated. Therefore, appropriate control of the grain size combined with Ca alloying of the Mg anode resulted in a remarkable electrochemical Mg2+/Mg0 cycling activity.


Synthetic studies towards congeners of phomactin A. Re-examination of the structure of Sch 49028.
The total syntheses of the epoxy cyclic hemiacetal structures 8 and 9, which are isomeric with the structure 6 proposed for the phomactin known as Sch 49028 isolated from the marine fungus Phoma sp. are described. Neither of these structures showed spectroscopic data consistent with those reported for the purported natural product, adding credibility to the proposal that the structure Sch 49028 does not exist in nature and that its NMR spectroscopic data should have been assigned as phomactin A (1).


User preferences and water use savings owing to washbasin taps retrofit: a case study of the DECivil building of the University of Aveiro.
During the last decades, achieving water efficiency in buildings has increasingly become an important challenge in the scope of sustainability. Water consumption is directly related to individual conduct. Despite the various technological improvements in fixtures and appliances, their performance will be influenced by human preferences and behavior. As a result, the potential for effective water consumption saving is influenced by behavior change as well as water-efficient fixtures and appliances. This work evaluates the impact of user preferences and behavior change on the water-efficient performance of tap aerators in a case study building: the Department of Civil Engineering building of the University of Aveiro, Portugal. Four aerators with different discharge reductions and types were installed in the toilet's washbasins and the user's preferences and behavior change measured through direct and online questionnaires. It was observed that the effective water consumption reduction (15 to 49%) was less than the discharge reduction (30 to 70%), confirming that user factors influence water savings. Water use reductions in the tested range (2.0 to 6.7 l/min) also varied according to gender, with male users using less water than their female counterparts. It was noted that an awareness of sustainability values prevailed amongst the users when confronted with the choice between comfort and water efficiency, although differences were observed in the user preferences regarding the various aerators. When confronted with the information that the lower discharge aerator would contribute to a reduction of about 70% on the water discharge, 25% of the users agreed with its use, even if it resulted in a certain degree of dissatisfaction. In comparison, only 8% of the users completely disagreed with its installation. On average, the water consumption reduction was 46% smaller than the discharge reduction achievable with the aerator alone. This further confirms the user factors inform the degree of water savings that is achievable from water-efficient fittings and fixtures.


A single-amino acid substitution in the sixth leucine-rich repeat of barley MLA6 and MLA13 alleviates dependence on RAR1 for disease resistance signaling.
Interactions between barley and the powdery mildew pathogen, Blumeria graminis f. sp. hordei, (Bgh) are determined by unique combinations of host resistance genes, designated Mildew-resistance locus (Ml), and cognate pathogen avirulence genes. These interactions occur both dependent and independent of Rar1 (required for Mla12 resistance) and Sgt1 (Suppressor of G-two allele of skp1), which are differentially required for diverse plant disease-resistance pathways. We have isolated two new functional Mla alleles, Rar1-independent Mla7 and Rar1-dependent Mla10, as well as the Mla paralogs, Mla6-2 and Mla13-2. Utilizing the inherent diversity amongst Mla-encoded proteins, we identified the only two amino acids exclusively conserved in RAR1-dependent MLA6, MLA10, MLA12, and MLA13 that differ at the corresponding position in RAR1-independent MLA1 and MLA7. Two- and three-dimensional modeling places these residues on a predicted surface of the sixth leucine-rich repeat (LRR) domain at positions distinct from those within the beta-sheets hypothesized to determine resistance specificity. Site-directed mutagenesis of these residues indicates that RAR1 independence requires the presence of an aspartate at position 721, as mutation of this residue to a structurally similar, but uncharged, asparagine did not alter RAR1 dependence. These results demonstrate that a single-amino acid substitution in the sixth MLA LRR can alter host signaling but not resistance specificity to B. graminis.


Synthesis, characterization, and anticancer evaluation of 1,3-bistetrahydrofuran-2yl-5-FU as a potential agent for pancreatic cancer.
The failure of current chemotherapeutic agents for pancreatic cancer (PCa) makes it the most aggressive soft tissue tumor with a 5-year survival of slightly above 10% and is estimated to be the second leading cause of cancer death by 2030. The main aim was to synthesize, characterize and evaluate the anticancer activity of 1,3-bistetrahydrofuran-2yl-5FU (MFU). MFU was synthesized by using 5-fluorouracil (5-FU) and tetrahydrofuran acetate, and characterized by nuclear magnetic resonance (NMR), micro-elemental analysis, high-performance liquid chromatography (HPLC), and liquid chromatography with mass spectrophotometry (LC-MS). MFU and Gemcitabine hydrochloride (GemHCl) were tested for antiproliferative activity against MiaPaca-2 and Panc-1 cell lines. The half-minimum inhibitory concentration (IC50) of MFU was twice lower than that of GemHCl when used in both cell lines. MiaPaca-2 cells (MFU-IC50 = 4.5 ± 1.2 μM vs. GemHCl-IC50 = 10.3 ± 1.1 μM); meanwhile similar trend was observed in Panc-1 cells (MFU-IC50 = 3.0 ± 1 μM vs. GemHCl-IC50 = 6.1 ± 1.03 μM). The MFU and GemHCl effects on 3D spheroids showed a similar trend (IC50-GemHCl = 14.3 ± 1.1 μM vs. IC50-MFU = 7.2 ± 1.1 μM) for MiaPaca-2 cells, and (IC50-GemHCl = 16.3 ± 1.1 μM vs. IC50-MFU = 9.2 ± 1.1 μM) for Panc-1 cells. MFU significantly inhibited clonogenic cell growth, and induced cell death via apoptosis. Cell cycle data showed mean PI for GemHCl (48.5-55.7) twice higher than MFU (24.7 to 27.9) for MiaPaca-2 cells, and similarly to Panc-1 cells. The in-vivo model showed intensely stained EGFR (stained brown) in all control, GemHCl and MFU-treated mice bearing subcutaneous PDX tumors, however, HER2 expression was less stained in MFU-treated tumors compared to GemHCl-treated tumors and controls. Mean tumor volume of MFU-treated mice (361 ± 33.5 mm3) was three-fold lower than GemHCl-treated mice (1074 ± 181.2 mm3) bearing pancreatic PDX tumors. MFU was synthesized with high purity and may have potential anticancer activity against PCa.


The EHEC type III effector NleL is an E3 ubiquitin ligase that modulates pedestal formation.
Enterohemorrhagic Escherichia coli (EHEC) O157:H7 causes hemorrhagic colitis and may result in potentially fatal hemolytic uremia syndrome in humans. EHEC colonize the intestinal mucosa and promote the formation of actin-rich pedestals via translocated type III effectors. Two EHEC type III secreted effectors, Tir and EspFu/TccP, are key players for pedestal formation. We discovered that an EHEC effector protein called Non-LEE-encoded Ligase (NleL) is an E3 ubiquitin ligase. In vitro, we showed that the NleL C753 residue is critical for its E3 ligase activity. Functionally, we demonstrated that NleL E3 ubiquitin ligase activity is involved in modulating Tir-mediated pedestal formation. Surprisingly, EHEC mutant strain deficient in the E3 ligase activity induced more pedestals than the wild-type strain. The canonical EPEC strain E2348/69 normally lacks the nleL gene, and the ectopic expression of the wild-type EHEC nleL, but not the catalytically-deficient nleL(C753A) mutant, in this strain resulted in fewer actin-rich pedestals. Furthermore, we showed that the C. rodentium NleL homolog is a E3 ubiquitin ligase and is required for efficient infection of murine colonic epithelial cells in vivo. In summary, our study demonstrated that EHEC utilizes NleL E3 ubiquitin ligase activity to modulate Tir-mediated pedestal formation.


Emergence of long distance bird migrations: a new model integrating global climate changes.
During modern birds history, climatic and environmental conditions have evolved on wide scales. In a continuously changing world, landbirds annual migrations emerged and developed. However, models accounting for the origins of these avian migrations were formulated with static ecogeographic perspectives. Here I reviewed Cenozoic paleoclimatic and paleontological data relative to the palearctic-paleotropical long distance (LD) migration system. This led to propose a new model for the origin of LD migrations, the 'shifting home' model (SHM). It is based on a dynamic perspective of climate evolution and may apply to the origins of most modern migrations. Non-migrant tropical African bird taxa were present at European latitudes during most of the Cenozoic. Their distribution limits shifted progressively toward modern tropical latitudes during periods of global cooling and increasing seasonality. In parallel, decreasing winter temperatures in the western Palearctic drove shifts of population winter ranges toward the equator. I propose that this induced the emergence of most short distance migrations, and in turn LD migrations. This model reconciliates ecologically tropical ancestry of most LD migrants with predominant winter range shifts, in accordance with requirements for heritable homing. In addition, it is more parsimonious than other non-exclusive models. Greater intrinsic plasticity of winter ranges implied by the SHM is supported by recently observed impacts of the present global warming on migrating birds. This may induce particular threats to some LD migrants. The ancestral, breeding homes of LD migrants were not 'northern' or 'southern' but shifted across high and middle latitudes while migrations emerged through winter range shifts themselves.


The genetic architecture of selection response. Inferences from fine-scale mapping of bristle number quantitative trait loci in Drosophila melanogaster.
Quantitative trait loci (QTL) affecting responses and correlated responses to selection for abdominal and sternopleural bristle number have been mapped with high resolution to the X and third chromosomes. Advanced intercross recombinant isogenic chromosomes were constructed from high and low selection lines in an unselected inbred background, and QTL were detected using composite interval mapping and high density transposable element marker maps. We mapped a total of 26 bristle number QTL with large effects, which were in or immediately adjacent to intervals previously inferred to contain bristle number QTL on these chromosomes. The QTL contributing to response to selection for high bristle number were not the same as those contributing to response to selection for low bristle number, suggesting that distributions of allelic effects per locus may be asymmetrical. Correlated responses were more often attributable to loose linkage than pleiotropy or close linkage. Bristle number QTL mapping to the same locations have been inferred in studies with different parental strains. Of the 26 QTL, 20 mapped to locations consistent with candidate genes affecting peripheral nervous system development and/or bristle number. This facilitates determining the molecular basis of quantitative variation and allele frequencies by associating molecular variation at the candidate genes with phenotypic variation in bristle number in samples of alleles from nature.


Local Clays from China as Alternative Hemostatic Agents.
In recent years, the coagulation properties of inorganic minerals such as kaolin and zeolite have been demonstrated. This study aimed to assess the hemostatic properties of three local clays from China: natural kaolin from Hainan, natural halloysite from Yunnan, and zeolite synthesized by our group. The physical and chemical properties, blood coagulation performance, and cell biocompatibility of the three materials were tested. The studied materials were characterized by using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), X-ray fluorescence spectroscopy (XRF), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). All three clays showed different morphologies and particle size, and exhibited negative potentials between pH 6 and 8. The TGA and DSC curves for kaolin and halloysite were highly similar. Kaolin showed the highest water absorption capacity (approximately 93.8% ± 0.8%). All three clays were noncytotoxic toward L929 mouse fibroblasts. Kaolin and halloysite showed blood coagulation effects similar to that exhibited by zeolite, indicating that kaolin and halloysite are promising alternative hemostatic materials.


Quality indicators for the prevention of cardiovascular disease in primary care.
To determine the feasibility and usefulness of collecting 9 previously described quality indicators of cardiovascular disease (CVD) prevention in primary care. Retrospective chart audit. Family health team in Hamilton, Ont, comprising approximately 30 000 patients and 25 physicians over 2 sites. A random sample of community-dwelling men who were 40 to 80 years of age and women who were 50 to 80 years of age on January 1, 2003, and who had complete physical examinations in 2003. The frequency with which quality indicators were collected during the complete physical examination, whether the collection of these indicators predicted subsequent collection of the same indicators, and physician or patient behavioural changes to reduce the risk of CVD. Of the 237 patient charts reviewed, 142 were of men and 95 were of women. Collection of most of the quality indicators was high (> 50%). Results were adjusted for age, sex, and family health team site. Measurements to check for obesity were collected more frequently in women, while blood pressure measurements and follow-up when required were completed more frequently in men. The relationship between the collection of an indicator and the subsequent times the same indicator was collected was not significant for any of the variables except excess alcohol consumption, in that collection of the excess alcohol consumption indicator led to a significant increase in subsequent collection of that same indicator (P = .0091). Age significantly predicted the number of times cholesterol and blood pressure were repeatedly checked (P = .0074 and P = .0077, respectively). The collection of these indicators was significantly associated with behavioural changes related to CVD prevention on the part of the patient or physician, with collection of the alcohol consumption indicator being the most likely to encourage subsequent behavioural changes. The only indicator to not reach statistical significance for subsequent changes was the cholesterol indicator (P = .08). The collection of previously described quality indicators for the primary prevention of CVD in Canada is feasible. Collection of the indicators does not generally predict short-term outcomes; however, collection of most indicators increased the odds of patient or physician behavioural changes for the primary prevention of CVD.


Pd-Catalyzed C-H arylation of pyridazine-based fused 1,2,4-triazoles: overriding selectivity at the usual position by undermining of preferred chelate formation.
The applicability of C-H functionalization to medicinally important 2-pyridyl-based N-heterocycles suffers from severe challenges owing to the high Lewis basicity of the N-atom. This arrests catalytic activity and yields undesirable positional selectivity due to preferential chelate formation. In this regard, we report a novel palladium(ii)-catalyzed arylation strategy on multiple-N-containing pyridazines by over-riding the functionalization due to a chelated palladacycle. We report a regioselective mono-arylation at the 8-position of diphenyl azolopyridazines without any ortho-C-H activation on the proximal phenyl groups. This methodology presents a broad arylation scope with uncompromised yield and positional selectivity, including the heteroarylation of N-heterocycles, which is an unprecedented feat for these types of molecules.


Effectiveness of magnetized water and 0.2% chlorhexidine as a mouth rinse in children aged 12-15 years for plaque and gingivitis inhibition during 3 weeks of supervised use: A randomized control study.
Chlorhexidine mouth rinse, a 'Gold Standard'effective in reducing plaque and gingivitis, has some drawbacks like bitter taste, light brown staining of teeth etc. limiting its long-term use. Magnetized water is alkaline and inhibits the bonding process between plaque and teeth by "magnetohydrodynamic". Aim: To compare and evaluate effectiveness of magnetized water and 0.2% chlorhexidine as a mouth rinse in children aged 12-15 years for plaque and gingivitis inhibition during 3 weeks of supervised use. Settings and Design: This was a double blinded randomized control clinical study, carried out at a non-government high school. Methods:A total of 20 children aged 12-15 years were randomized into two groups, magnetized water and 0.2% chlorhexidine, each comprising of 10 children who were asked to rinse with the respective mouthwash. Plaque index (PI) scoresand gingival (GI) scoreswere evaluated at baseline, 2 weeks and at 3 weeksfor each child. Statistical analysis: Independent sample t test and paired sample t test were used to check the mean differences. Result: A statistically significant difference was found in reduction of mean PI and GI scores of magnetized water (p=0.0001) and Chlorhexidine groups(p=0.0001) both at 14 days (2 weeks) and at 21 days (3 weeks) with no adverse effects. Conclusion: Daily use of magnetized water as a mouth rinse was safe andeffective alternative to chlorhexidinein plaque and gingivitis reduction, which supplemented the benefits of daily toothbrushing in children.


Headache in the Diagnosis-Related Groups (DRG) era: management and appropriateness of admission.
Headache is an extremely common disorder which has a marked impact on the utilisation of healthcare resources and constitutes a considerable socio-economic burden. The related costs, both direct and indirect, are especially high in developed countries, since headache predominantly affects an economically-active section of the population. The Diagnosis-Related Groups (DRG) system, a method for reimbursing healthcare structures for patient admissions, was introduced in Italy in 1995. The aim of the system was to control public health expenditure and to promote better distribution of financial resources. Here, we report the results of the application of the DRG system to headache patients admitted to the Department of Neurology of the University of Pavia in 1996 and 1998. The financial analysis revealed high fixed costs (hospital running costs per days of hospitalisation); by contrast, the impact of the variable costs (those relating to the direct management of the individual patient, i.e. examinations, therapeutic interventions etc.) was low. It was found that reducing the number of days of hospitalisation increases the hospital's income and reduces the mean loss incurred in each DRG. It is therefore suggested that a complete approach to the management of headache must include educational programmes for patients and general practitioners, and that access to headache centres and to hospital care should be restricted to cases of acute, severe headache, or recurrent, chronic headache with/without drug abuse or dependence.


The experimental research of nerve fibers compensation amplification innervation of ulnar nerve and musculocutaneous nerve in rhesus monkeys.
This experiment intended to authenticate the compensation and amplification effect of regenerated nerve fibers after nerve injury in primate. The Rhesus Monkeys right ulnar nerves and musculocutaneous nerves were chosed. The proximal impaired ulnar nerve as the proximal end and the distal impaired ulnar nerve musculocutaneous nerve as the distal ends. The ulnar nerve proximal stump fibers can grow into both the ulnar nerve distal stump and the musculocutaneus nerve at the same time and established two different electrophysiological conduction passageway. There exist nerve fibers compensation amplification effect after peripheral nerve injury on Rhesus Monkeys.


Cell adaptation of the extremophilic red microalga Galdieria sulphuraria to the availability of carbon sources.
Global energy demand and fossil fuels impact on climate can be partially managed by an increase in the use of biofuels for transports and industries. Biodiesel production is generally preceded by a transesterification process of the green biomass triacylglycerols that generates large amounts of glycerol as a by-product. In this study, the extremophilic red microalga Galdieria sulphuraria 074W was cultivated in heterotrophy. The microalgal growth parameters and biomass composition were compared when grown on an equivalent molar concentration of carbon of either glucose or glycerol as unique carbon source. The maximal biomass reached in these two conditions was not significantly different (∼2.5 g.L-1). Fatty acid profile, protein and storage carbohydrate contents were also statistically similar, irrespectively of the metabolized carbon source. We also observed that the pigment content of G. sulphuraria cells decreased during heterotrophic growth compared to photoautotrophic cultivated cells, and that this diminution was more important in the presence of glucose than glycerol: cells were yellowish in the presence of glucose and green in the presence of glycerol. The pigmentation was restored when glucose was totally consumed in the medium, suggesting that the presence of glucose repressed pigment synthesis. Based on this observation, a transcriptome analysis was performed in order to better understand the mechanisms involved in the loss of color mediated by darkness and by glucose in G. sulphuraria. Three conditions were analyzed: heterotrophy with glycerol or glucose and phototrophy. This allowed us to understand the transcriptional response of cells to light and dark environments both at the nuclear and chloroplast levels, and to show that transcription of gene families, acquired by horizontal gene transfer, such as sugar, amino acid, or acetate transporters, were involved in the response to the availability of different (in)organic sources.


Role of ankle taping and bracing in the athlete.
Adhesive tape is often used to help athletes recover from ligament sprains of the ankle or to prevent further injury. The choice of taping technique or material is often decided by personal preference, superstition, or anecdote. More recently, the use of ankle braces has become more prevalent, but reasons for their use are similarly variable. As ankle sprains are a major cause of an athlete's disability and time off sport, the choice of the method of support should be more scientifically reasoned. This paper attempts to review the literature concerning the effects of various methods of ankle support on swelling, stability, range of movement, proprioception, muscle function, gait, and performance tests. There is still some contradiction in the literature about the effects of taping and braces in both the acute and chronic phases of ligament sprains of the ankle.


Preference of RIG-I for short viral RNA molecules in infected cells revealed by next-generation sequencing.
Intracellular detection of virus infections is a critical component of innate immunity carried out by molecules known as pathogen recognition receptors (PRRs). Activation of PRRs by their respective pathogen-associated molecular patterns (PAMPs) leads to production of proinflamatory cytokines, including type I IFN, and the establishment of an antiviral state in the host. Out of all PRRs found to date, retinoic acid inducible gene I (RIG-I) has been shown to play a key role in recognition of RNA viruses. On the basis of in vitro and transfection studies, 5'ppp RNA produced during virus replication is thought to bind and activate this important sensor. However, the nature of RNA molecules that interact with endogenous RIG-I during the course of viral infection has not been determined. In this work we use next-generation RNA sequencing to show that RIG-I preferentially associates with shorter, 5'ppp containing viral RNA molecules in infected cells. We found that during Sendai infection RIG-I specifically bound the genome of the defective interfering (DI) particle and did not bind the full-length virus genome or any other viral RNAs. In influenza-infected cells RIG-I preferentially associated with shorter genomic segments as well as subgenomic DI particles. Our analysis for the first time identifies RIG-I PAMPs under natural infection conditions and implies that full-length genomes of single segmented RNA virus families are not bound by RIG-I during infection.


Different treatment modalities for refractory vaginismus in western Saudi Arabia.
Although vaginismus is a common sexual dysfunction in Saudi Arabia, there are limited data concerning the treatment modalities associated with patients with symptoms of vaginismus. This study is aimed to evaluate the presentation and different modalities of management in patients with severe refractory vaginismus in western Saudi Arabia. Successful penetrative sexual intercourse suggesting that common elements of the therapies used were successful. A retrospective study of patients presenting with severe refractory vaginismus treated in Jeddah, Saudi Arabia. The subjects were 15 women with third to fourth degree vaginismus who presented to King Abdulazziz University Hospital between January 1, 2008 and January 1, 2009. The mean age of the participants was 23 years. The mean duration of marriage before seeking medical advice was 12 months. Six patients had undergone conventional therapy successfully. The other six cases, four of which had a previous history of treatment failure, and two who were unresponsive to 4 months of conventional therapy were offered botulinum toxin type A. Five patients who received the Botox therapy had satisfactory intercourse on the same day of the treatment. One patient required a repeat injection after 2 months for recurrent vaginismus. Three of the 15 patients refused the treatment as they were already divorced and had only come in to exclude organic causes for their condition. Vaginismus is an overlooked topic in conservative societies such as Saudi Arabia. For most patients, not knowing who to confide in or where to turn to plays a major role in the under diagnosis of vaginismus. Conventional therapy proved effective in mild and moderate cases, while botulinum toxin has a more rapid effect and was thus more effective in severe cases.


Practical Entropy Accumulation for Random Number Generators with Image Sensor-Based Quantum Noise Sources.
The efficient generation of high-quality random numbers is essential in the operation of cryptographic modules. The quality of a random number generator is evaluated by the min-entropy of its entropy source. The typical method used to achieve high min-entropy of the output sequence is an entropy accumulation based on a hash function. This is grounded in the famous Leftover Hash Lemma, which guarantees a lower bound on the min-entropy of the output sequence. However, the hash function-based entropy accumulation has slow speed in general. For a practical perspective, we need a new efficient entropy accumulation with the theoretical background for the min-entropy of the output sequence. In this work, we obtain the theoretical bound for the min-entropy of the output random sequence through the very efficient entropy accumulation using only bitwise XOR operations, where the input sequences from the entropy source are independent. Moreover, we examine our theoretical results by applying them to the quantum random number generator that uses dark shot noise arising from image sensor pixels as its entropy source.


CYFRA 21-1 as a tumor marker for squamous cell carcinoma of the esophagus.
This study assessed the clinical value of CYFRA 21-1 in comparison with squamous cell carcinoma antigen (SCC-Ag), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) in patients with esophageal squamous cell carcinoma. In 112 primary cancer patients, the diagnostic sensitivity of CYFRA 21-1 (33.9%) was superior to SCC-Ag (28.6%), CEA (12.5%), and CA19-9 (6.3%). Levels of CYFRA 21-1 were closely correlated with TNM stage and were below the cutoff value in all 21 patients with stage I disease. All 38 patients with a CYFRA 21-1 level over the cutoff value among the 80 patients who underwent esophagectomy had lymph node metastases (pNl). A correlation was found between CYFRA 21-1 levels and clinical response in serial measurements of 21 patients who received chemotherapy or chemo radiotherapy. Our findings suggest that CYFRA 21-1 is not useful for diagnosis, but that it is valuable for monitoring the efficacy of therapy.


Neonatal testicular torsion.
Rotation of the testis around the axis of the spermatic cord results in tissue ischaemia and testicular torsion (TT). TT in the newborn infant in the 1st month of life is referred to as neonatal TT (NTT) or perinatal TT and occurs in 6.1/100, 000 live births. The true incidence could be higher as some of these occur prenatally and can be asymptomatic. TT can be extravaginal, intravaginal and mesorchial and NTT is usually extravaginal. Physical examination can be adequate for the diagnosis, and utility of ultrasound (US) is mainly to exclude other conditions. If the timing of the torsion is prenatal, the testicle may not be salvageable. But, in certain situations, these could be asymptomatic bilateral TT. When the timing of torsion is not simultaneous (asynchronous torsion) early contralateral orchiopexy done at the time of exploration would prevent the occurence of asynchronous torsion. Non.operative maneuvres to detorse in NTT are not successful and not recommended. This review focuses on the diagnostic approach and management.


Peer review and journal impact factor: the two pillars of contemporary medical publishing.
The appraisal of scientific quality is a particularly difficult problem. Editorial boards resort to secondary criteria including crude publication counts, journal prestige, the reputation of authors and institutions, and estimated importance and relevance of the research field, making peer review a controversial rather than a rigorous process. On this background different methods for evaluating research may become required, including citation rates and journal impact factors (IF), which are thought to be more quantitative and objective indicators, directly related to published science. The aim of this review is to go into the two pillars of contemporary medical publishing, that is the peer review process and the IF. Qualified experts' reviewing the publications appears to be the only way for the evaluation of medical publication quality. To improve and standardise the principles, procedures and criteria used in peer review evaluation is of great importance. Standardizing and improving training techniques for peer reviewers, would allow for the magnification of a journal's impact factor. This may be a very important reason that impact factor and peer review need to be analyzed simultaneously. Improving a journal's IF would be difficult without improving peer-review efficiency. Peer-reviewers need to understand the fundamental principles of contemporary medical publishing, that is peer-review and impact factors. The current supplement of the Hippokratia for supporting its seminar for reviewers will help to fulfil some of these scopes.


Comparative study on the acceptability of two modern monophasic oral contraceptive preparations: 30 microgram ethinyl estradiol combined with 150 microgram desogestrel or 75 microgram gestodene.
Cycle control and tolerability of two monophasic oral contraceptive pills containing 30 microg ethinyl estradiol (EE) with either 150 microg desogestrel (DSG) or 75 microg gestodene (GSD) were compared in women starting oral contraception. A minimum of 200 healthy women at risk for pregnancy were to be treated for a total of 6 cycles per patient in a prospective, randomized open parallel-group multicenter trial. Two hundred and forty-one subjects were randomized, 115 to DSG/EE and 126 to GSD/EE. Compliance to the study preparation was high (around 95%) in both groups and no pregnancies occurred during the study. Cycle control was excellent; there were no differences between the two groups with regard to incidence of spotting and breakthrough bleeding or duration and intensity of withdrawal bleeding. Side-effects were mild and in general comparable in the two groups. Both at baseline and during treatment, a higher proportion of women taking GSD/EE complained about breast tenderness. This resulted in more early withdrawals because of breast tenderness in the GSD/EE group. It was concluded that monophasic DSG/EE and GSD/EE are equally effective, have similar cycle control and both are generally well tolerated.


Alterations in gene expression during radiation-induced mitotic catastrophe in HeLa Hep2 cells.
To explore kinetic changes in the gene expression profile during radiation-induced mitotic catastrophes. Gene expression changes were measured in HPV-infected HeLa Hep2 tumor cells following exposure to 5 Gy of ionizing radiation ((60)Co). Signaling pathways were explored and correlated to the biological responses linked to mitotic catastrophe. Following irradiation a transient G2-arrest was induced. Anaphase bridge formation and centrosome hyperamplification was observed. These phenotypical changes correlated well with the observed gene expression changes. Genes with altered expression were found to be involved in mitotic processes as well as G2- and spindle assembly checkpoints. Also centrosome-associated genes displayed an increased expression. This study elucidates specific characteristics in the altered gene expression pattern induced by irradiation, which can be correlated to the events of mitotic catastrophe in HeLa Hep2 cells. Therapeutic strategies modulating these alterations might potentiate future therapy and enhance tumor cell killing.


[Outcomes of transcutaneous posterior tibial nerve stimulation for overactive bladder in diabetic patients].
Treatment with transcutaneous posterior tibial neurostimulation (NTPT) has been shown to be effective in the treatment of overactive bladder (OAB), but its outcomes in diabetic patients have never been assessed. The aim of this study was to compare the efficacy of NTPT in diabetic OAB patients and in OAB patients without diabetes. A single-center prospective study included all patients treated with NTPT for lower urinary tract storage symptoms between 2012 and 2016. The primary endpoint was symptoms improvement≥50% assessed using a Visual Analog Scale (VAS) two months after starting NTPT. Treatment consisted in a daily 20-minute NTPT single-session. The secondary endpoints were lower urinary tract symptoms reported by bladder diary, the Urinary Symptom Profile, the impact on mood and on daily activities. Seventy-one patients were included, 10 of whom were diabetic. The efficacy rate (EVA>50%) was not significantly different in the diabetic group (70% vs. 44.1%, P=0.17), like the mean EVA efficacy was similar in both groups (4/10 vs. 4/10, P=0.98). OAB USP sub-score diminished significantly in both groups at 2 months (-3 points in the diabetic group; -1.9 points in the non-diabetic group; P=0.03 and P<0.0001, respectively). There was no significant difference between the groups, except for the rate of patients who stopped treatment at 6 months, higher in diabetic patients (100% vs. 63.5%, P=0.04). The functional outcomes of NTPT appear to be similar in the treatment of OAB in diabetic patients and in non-diabetic patients. 4.


Protection against hypoxic injury in isolated-perfused rat heart by ruthenium red.
Changes in intracellular calcium content and energy production during the period of hypoxia appear to be necessary for the development of cellular injury. Ruthenium red, a hexavalent dye which inhibits the active uptake of calcium by mitochondria, might improve a cell's energy status thereby minimizing hypoxic injury. Rat heart tissue was perfused retrogradely with Krebs-Henseleit medium containing 2.5 mM calcium and 10 mM glucose. The infusion of 0.1, 1.0 or 1.24, but not 0.01 microM, ruthenium red throughout 60 min of hypoxia and 30 min of reoxygenation decreased, in a dose-dependent manner, the release of lactate dehydrogenase normally seen at reoxygenation. When the infusion of 1.24 microM ruthenium red was begun after 45 min of hypoxia, lactate dehydrogenase release at reoxygenation after 60 min of hypoxia was decreased, but to a lesser extent than when this agent was present throughout hypoxia. Ruthenium red, 1.24 microM, had no significant effects on coronary flow or function in oxygenated heart tissue. When present throughout hypoxia and reoxygenation, 1.24 microM ruthenium red prevented the decrease in coronary flow normally seen and allowed recovery of heart rate, +dP/dT, -dP/dT and work (defined as the product of developed pressure and heart rate) to normal levels. Significant functional protection was not evident at reoxygenation when ruthenium red was infused after 45 min of hypoxia or in the absence of glucose. Cardiac ATP, creatine phosphate and energy charge were decreased after 60 min of hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)


Combined pirfenidone, azithromycin and prednisolone in post-H1N1 ARDS pulmonary fibrosis.
There are no specific data on the management of pulmonary fibrosis post-H1N1 ARDS. We present the cases of three patients who responded positively to treatment with pirfenidone, azithromycin and prednisolone. Three males, aged 40, 45 and 59 years, had H1N1 ARDS requiring mechanical ventilation for two weeks or longer. After weaning off ventilation, they had persistent symptoms and hypoxemia at rest despite receiving prednisolone and home oxygen for at least three weeks following discharge. Computed tomography (CT) of the chest showed fibrosis and traction bronchiectasis. At presentation, they could not perform spirometry. Investigations ruled out infection. Pirfenidone (600 mg daily escalated to maximum tolerable dose of 2.4 gm daily) and azithromycin (500 mg thrice weekly) were added off-label to prednisolone. In one patient pirfenidone was discontinued after three months due to an adverse reaction and azithromycin was continued for nine months. At one year follow-up, all patients had symptomatic improvement, better effort tolerance, regression of opacities and no progression of fibrosis on CT, and improvement in spirometry and six minute walk tests. Pirfenidone and azithromycin added to prednisolone may have led to clinical and radiological improvement. The current experience suggests that this treatment approach to pulmonary fibrosis post-H1N1 ARDS be studied further. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 85-90).


Cellular immune responses to human papillomavirus (HPV)-16 L1 in healthy volunteers immunized with recombinant HPV-16 L1 virus-like particles.
The causal association between papillomavirus (HPV) infection and cervical cancer has been demonstrated; the development of a prophylactic vaccine to protect against HPV infection may therefore reduce the incidence of this cancer worldwide. Noninfectious HPV-like particles (VLPs), composed of the L1 major capsid protein, are current candidate vaccines for prevention of HPV infection and cervical neoplasia. Although neutralizing antibodies have a pivotal role in the prevention of initial infection, cellular immune responses to HPV antigens may have an important role in viral clearance. A phase II trial was conducted to further evaluate the immunogenicity of a recombinant HPV-16 L1 VLP vaccine administered intramuscularly, without adjuvant, at 0, 1, and 6 months. Cell-mediated immune responses (lymphoproliferation and cytokine production) to HPV-16 L1 VLPs were evaluated in peripheral blood mononuclear cells (PBMCs) from 43 individuals receiving the L1 VLP vaccine and from 10 individuals receiving placebo. Vaccination resulted, at months 2 and 7 (i.e., 1 month after the second immunization and 1 month after third immunization, respectively), in increases in T cell-proliferative response to HPV-16 L1 VLPs (P<.001). In addition, significant increases in cytokine (interferon-gamma, interleukin [IL]-5 and IL-10) responses to L1 VLPs were observed after vaccination (P<.001). The strongest cytokine responses at month 7 were observed in individuals with high antibody titers at month 2, suggesting that neutralizing antibodies generated by initial vaccination may augment T cell responses to subsequent booster vaccinations. No significant increases in lymphoproliferative or cytokine responses to L1 VLPs were observed in individuals receiving placebo. In summary, the HPV-16 L1 vaccine induces not only robust B cell responses but also L1-specific T cell responses detectable by proliferation of both CD4+ and CD8+ T cells and in vitro production of both Th1- and Th2-type cytokines. Future efficacy studies are needed to evaluate whether and/or how VLP vaccines confer protection against genital HPV infection and associated disease.


The weeping behavior in anorexic and bulimic females.
The aim of the study was to examine the proneness, the functions and triggering situations of weeping in anorexic and bulimic women. Participants were 36 anorexic and 31 bulimic female patients and 56 age-matched female controls. All women completed the Questionnaire on Adult Crying. We limited our study to results on 'crying proneness', 'functions of crying' and 'determining factors of crying'. Bulimic patients reported to have cried significantly more often in the last 4 weeks, to be more likely to cry in situations of distress and to have used weeping significantly more often as a manipulative behavior than control women. Anorexic patients rated their tendency to cry significantly lower and experienced weeping as significantly more negative than controls. Compared to control women, anorexic patients associated weeping with negative feelings as opposed to bulimic patients who appeared to use weeping on an intentional basis. These deviations from control women seem to mirror the introvert character of anorexic patients and the extrovert impulsive personality of patients with bulimia nervosa, respectively.


[Effect of type of starch and quantity in rations on apparent and true digestibility of nitrogen and nitrogen balance in sheep].
In a digestibility trial 5 semisynthetic rations were fed in 3 periods to 10 male sheep to examine the effects on N balance, components of faecal nitrogen and N digestibility. The rations contained constant amounts of nitrogen but different contents of cellulose and two different types of starch (untreated and steamflaked). Content and type of starch did not show any noticeable effect neither on excretion of undigested dietary nitrogen nor on true digestibility. There could not be noticed any effects on the apparent N digestibility by changing contents of cellulose or untreated starch. If the rations contained steamflaked corn starch, the animals excreted more faecal nitrogen and therefore showed a lower apparent N digestibility. Especially the water soluble N fraction of the faecal nitrogen was clearly higher. Compensation took place through a lower N excretion with the urine. The reason for increased faecal N excretion may be higher microbial protein synthesis in the rumen. This was accented by the allantoin excretion with the urine.


Stable to improved cardiac and pulmonary function in children with high-risk sickle cell disease following haploidentical stem cell transplantation.
Children with sickle cell disease (SCD) are at high-risk of progressive, chronic pulmonary and cardiac dysfunction. In this prospective multicenter Phase II trial of myeloimmunoablative conditioning followed by haploidentical stem cell transplantation in children with high-risk SCD, 19 patients, 2.0-21.0 years of age, were enrolled with one or more of the following: history of (1) overt stroke; (2) silent stroke; (3) elevated transcranial Doppler velocity; (4) multiple vaso-occlusive crises; and/or (5) two or more acute chest syndromes and received haploidentical transplants from 18 parental donors. Cardiac and pulmonary centralized cores were established. Pulmonary function results were expressed as percent of the median of healthy reference cohorts, matched for age, sex, height and race. At 2 years, pulmonary functions including forced expiratory volume (FEV), FEV1/ forced vital capacity (FVC), total lung capacity (TLC), diffusing capacity of lung for carbon monoxide (DLCO) were stable to improved compared to baseline values. Importantly, specific airway conductance was significantly improved at 2 years (p < 0.004). Left ventricular systolic function (fractional shortening) and tricuspid regurgitant velocity were stable at 2 years. These results demonstrate that haploidentical stem cell transplantation can stabilize or improve cardiopulmonary function in patients with SCD.


Formal thought disorder in non-clinical individuals with auditory verbal hallucinations.
Auditory verbal hallucinations (AVH) and formal thought disorder (FTD) may originate from the same aberration in the language system. The hypothesis of a shared neurobiological basis would be strengthened by the presence of FTD in individuals who frequently experience AVH, but do not meet DSM-IV criteria for a psychotic disorder. In this study, FTD was quantified in 40 non-clinical subjects with AVH, in 50 healthy subjects without AVH and in 40 schizophrenia patients with AVH. Recorded speech samples were analysed by one rater who was blind to the presence/absence of AVH and to diagnosis, using the Thought and Language Index. Negative FTD was barely present in non-clinical subjects with AVH and in healthy controls without AVH. Positive FTD, however, was significantly higher in both groups experiencing AVH than in controls without AVH. Severity of positive FTD did not differ significantly between non-clinical subjects with AVH and schizophrenia patients with AVH. Negative FTD (alogia) appears not to be associated with AVH. However, the fact that positive FTD (disorganised speech) in schizophrenia patients with AVH is equally high in non-clinical subjects with AVH indicates that these two symptoms tend to co-occur, which may be suggestive of a shared neurobiological substrate.


Oral health and treatment needs in institutionalized psychiatric patients in India.
The caries prevalence, oral hygiene status, periodontal health and treatment needs were evaluated in a group of institutionalized psychiatric patients in Goa, India. Of the total 153 inmates, males constituted 59 percent, the mean age was 25 years, 96 percent were self sufficient and the response rate was 84 percent. 63 percent were diagnosed with schizophrenia. They did not receive any assistance in daily self-care activities including oral hygiene maintenance. None of the 5 edentulous patients had dentures, 5% had been referred for emergency dental care during the period of institutionalization. 15 subjects (12%) were caries-free, the stepwise linear regression analysis showed that the mean DMFT index significantly increased with age (t = 2-819, PL 0.05). Two third of the study population (88%) were in need of conservative dental treatment. The stepwise linear regression analysis showed that the mean OHI-S index significantly increased with age (t = 2.412, P < 0.01). Only 5.4% reported a healthy periodontium whereas 16.27% required complex periodontal therapy. Soft tissue lesions included dorsal lingual depapillation/heavily coated areas and angular cheilitis in addition to incidental observations such as mucosal hyperpigmentation, gingival hyperplasia, and leucoedema. Bruxism and factitious injuries were also noted. The onus of meeting the oral health needs of this marginalized patient population therefore depends on the effectiveness of community dentistry programs vis a vis the efforts of the staff of the institution to provide such services on a regular basis.


The prevalence of joint contractures, pressure sores, painful shoulder, other pain, falls, and depression in the year after a severely disabling stroke.
Complications after stroke have been shown to impede rehabilitation, lead to poor functional outcome, and increase cost of care. This inception cohort study sought to investigate the prevalence of immobility-related complications during the first year after severely disabling stroke in relation to functional independence and place of residence. Over a 7-month period, 600 stroke survivors were identified in the hospital through the Nottingham Stroke Register. Those who had a Barthel Index score <or=10 3 months poststroke and did not have a primary diagnosis of dementia were eligible to participate in the study. Assessments of complications were carried out at 3, 6, and 12 months poststroke. Complications were recorded for 122 stroke survivors (mean age, 76 years; 57% male). Sixty-three (52%) had significant language impairment and of the remaining 59 who were able to complete an assessment of cognitive function, 10 (8%) were cognitively impaired. The numbers of reported complications over 12 months, in rank order, were falls, 89 (73%); contracture, 73 (60%); pain, 67 (55%); shoulder pain, 64 (52%); depression, 61 (50%); and pressure sores, 26 (22%). A negative correlation was found between Barthel Index score and the number of complications experienced (low scores on the Barthel Index correlate with a high number of complications). The highest relative percentages of complications were experienced by patients who were living in a nursing home at the time of their last completed assessment. Immobility-related complications are very common in the first year after a severely disabling stroke. Patients who are more functionally dependent in self-care are likely to experience a greater number of complications than those who are less dependent. Trials of techniques to limit and prevent complication are required.


Cross-talk between notch and the estrogen receptor in breast cancer suggests novel therapeutic approaches.
High expression of Notch-1 and Jagged-1 mRNA correlates with poor prognosis in breast cancer. Elucidating the cross-talk between Notch and other major breast cancer pathways is necessary to determine which patients may benefit from Notch inhibitors, which agents should be combined with them, and which biomarkers indicate Notch activity in vivo. We explored expression of Notch receptors and ligands in clinical specimens, as well as activity, regulation, and effectors of Notch signaling using cell lines and xenografts. Ductal and lobular carcinomas commonly expressed Notch-1, Notch-4, and Jagged-1 at variable levels. However, in breast cancer cell lines, Notch-induced transcriptional activity did not correlate with Notch receptor levels and was highest in estrogen receptor alpha-negative (ERalpha(-)), Her2/Neu nonoverexpressing cells. In ERalpha(+) cells, estradiol inhibited Notch activity and Notch-1(IC) nuclear levels and affected Notch-1 cellular distribution. Tamoxifen and raloxifene blocked this effect, reactivating Notch. Notch-1 induced Notch-4. Notch-4 expression in clinical specimens correlated with proliferation (Ki67). In MDA-MB231 (ERalpha(-)) cells, Notch-1 knockdown or gamma-secretase inhibition decreased cyclins A and B1, causing G(2) arrest, p53-independent induction of NOXA, and death. In T47D:A18 (ERalpha(+)) cells, the same targets were affected, and Notch inhibition potentiated the effects of tamoxifen. In vivo, gamma-secretase inhibitor treatment arrested the growth of MDA-MB231 tumors and, in combination with tamoxifen, caused regression of T47D:A18 tumors. Our data indicate that combinations of antiestrogens and Notch inhibitors may be effective in ERalpha(+) breast cancers and that Notch signaling is a potential therapeutic target in ERalpha(-) breast cancers.


[Improvement of clinical parameters in a patient with metabolic syndrome through intervention in nutrition education and improvement of lifestyle].
The main objective is the reduction of early morbidity and mortality associated with metabolic syndrome (MS). 24h intakes count for 3 days and clinical-nutritional history. Follow-up of 19 visits to monitor the evolution. Following weight loss, the measurement of capillary blood glucose was 59 mg/dl, discontinuing then treatment with metformin; after 7 days without metformin treatment the value was 64 mg/dl. Intervention in nutritional education and lifestyle contributed to almost a 10% reduction of body weight; the patient moved from the obesity BMI range to overweight. Peripheral insulin resistance was also enhanced and the GP in charge decided to discontinue the dosing of metformin as a result.


Spectrum of steroid-resistant and congenital nephrotic syndrome in children: the PodoNet registry cohort.
Steroid-resistant nephrotic syndrome is a rare kidney disease involving either immune-mediated or genetic alterations of podocyte structure and function. The rare nature, heterogeneity, and slow evolution of the disorder are major obstacles to systematic genotype-phenotype, intervention, and outcome studies, hampering the development of evidence-based diagnostic and therapeutic concepts. To overcome these limitations, the PodoNet Consortium has created an international registry for congenital nephrotic syndrome and childhood-onset steroid-resistant nephrotic syndrome. Since August of 2009, clinical, biochemical, genetic, and histopathologic information was collected both retrospectively and prospectively from 1655 patients with childhood-onset steroid-resistant nephrotic syndrome, congenital nephrotic syndrome, or persistent subnephrotic proteinuria of likely genetic origin at 67 centers in 21 countries through an online portal. Steroid-resistant nephrotic syndrome manifested in the first 5 years of life in 64% of the patients. Congenital nephrotic syndrome accounted for 6% of all patients. Extrarenal abnormalities were reported in 17% of patients. The most common histopathologic diagnoses were FSGS (56%), minimal change nephropathy (21%), and mesangioproliferative GN (12%). Mutation screening was performed in 1174 patients, and a genetic disease cause was identified in 23.6% of the screened patients. Among 14 genes with reported mutations, abnormalities in NPHS2 (n=138), WT1 (n=48), and NPHS1 (n=41) were most commonly identified. The proportion of patients with a genetic disease cause decreased with increasing manifestation age: from 66% in congenital nephrotic syndrome to 15%-16% in schoolchildren and adolescents. Among various intensified immunosuppressive therapy protocols, calcineurin inhibitors and rituximab yielded consistently high response rates, with 40%-45% of patients achieving complete remission. Confirmation of a genetic diagnosis but not the histopathologic disease type was strongly predictive of intensified immunosuppressive therapy responsiveness. Post-transplant disease recurrence was noted in 25.8% of patients without compared with 4.5% (n=4) of patients with a genetic diagnosis. The PodoNet cohort may serve as a source of reference for future clinical and genetic research in this rare but significant kidney disease.


Comprehensive computerized diabetes registry. Serving the Cree of Eeyou Istchee (eastern James Bay).
Diabetes is rapidly evolving as a major health concern in the Cree population of eastern James Bay (Eeyou Istchee). The Cree Board of Health and Social Services of James Bay (CBHSSJB) diabetes registry was the initial phase in the development of a comprehensive program for diabetes in this region. The CBHSSJB diabetes registry was developed to provide a framework to track the prevalence of diabetes and the progression of diabetic complications. The database will also identify patients not receiving appropriate clinical and laboratory screening for diabetic complications, and will provide standardized clinical flow sheets for routine patient management. The CBHSSJB diabetes registry uses a system of paper registration forms and clinical flow sheets kept in the nine community clinics. Information from these sheets is entered into a computer database annually. The flow sheets serve as a guideline for appropriate management of patients with diabetes, and provide a one-page summary of relevant clinical and laboratory information. A diabetes registry is vital to follow the progression of diabetes and diabetic complications in the region served by the CBHSSJB. The registry system incorporates both a means for regional epidemiologic monitoring of diabetes mellitus and clinical tools for managing patients with the disease.


Predictors of extubation in the operating room after pediatric cardiac surgery: A single-center retrospective study.
In this study, we aimed to evaluate the outcomes of our on-table extubation strategy in patients with congenital heart disease. Between April 2021 and November 2022, a total of 114 pediatric patients (58 males, 56 females; median age: 25.3 months; range, 57.5 to 4.4 months) who were operated for congenital heart diseases were retrospectively analyzed. The patients were evaluated according to the Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STS-EACTS) scoring system. Perioperative patient data were analyzed and correlated with the extubation status. Overall, 56% of the patients were extubated in the operating room. There was an association between fluid balance per unit body surface area, longer cardiopulmonary bypass and cross-clamp times and on-table extubation. Lactate value prior to extubation, STS-EACTS mortality category, estimated mortality, and estimated morbidity were statistically significant with regards to the achievability of extubation. Multivariate analysis revealed lactate value prior to extubation and estimated postoperative length of hospital stay to be significant factors affecting on-table extubation. There was a significant correlation between decreased length of intensive care unit and hospital stay and on-table extubation. The outcomes of our on-table extubation strategy for patients with congenital heart disease reveal the feasibility of this approach. Higher lactate and fluid balance/body surface area levels, longer cross-clamp and cardiopulmonary bypass durations, increased surgical complexity are indicators of a failure to perform on-table extubation. This strategy is also associated with shorter intensive care unit and hospital length of stays as an additional clinical benefit.


Biomarkers--a pot of gold or a can of worms?: Meeting report from the 2nd World Congress on Biomarkers & Clinical Research, 2011, Baltimore, USA.
Biomarkers are biological agents used as indicators of biological states. In clinical applications, biomarkers reflect the presence, severity, or progression of disease states. They may also predict risk or responsiveness of a disease to a given treatment. There has been increasingly intense research interest in biomarkers, yet their translation into routine clinical use is lagging. To stimulate communication and cross-fertilization, the 2nd World Congress on Biomarkers & Clinical Research was held in Baltimore, MD, USA in 2011. The symposium covered a broad range of basic and applied biomarker research with the intent to facilitate bench-to-bedside developments. Sessions discussed DNA-based, proteomic, and blood-borne markers. The presentations covered biomarkers for cancer, other various diseases, and toxicological agents. Other topics included biomarker data assimilation, validation, standardization and quality control, as well as molecular imaging and informatics. New high-throughput assays, model systems and emerging technologies give reasons to hope for further rapid progress in the field.


Attempting to Define Clinical Productivity Metrics among Pediatric Palliative Care Services at Academic Children's Hospitals.
Introduction: Pediatric palliative care (PPC) programs have grown in size and number at academic children's hospitals in the United States for the past 20 years. Little is known about the relationships between program workforce staffing, billing and coding practices, clinical service requirements for billing providers, and sustainability of program models for billing providers. Methods: The authors contacted a convenience sample of 10 PPC program leaders at academic children's hospitals in the United States. Program leaders were asked to provide information about billing provider full-time equivalent (FTE) staffing, billing and coding practices, and productivity metrics for a three-month period, from January 1 to March 31, 2017. Results: Ten programs participated in the convenience sample survey, and seven provided information about billing and coding practices. For the seven programs that provided evaluation and management data, calculated estimate of mean work Relative Value Unit (wRVU) production per 1.0 FTE per year was 1626. Calculated estimate of consultations per 1.0 FTE per month was 15. Calculated estimate of total clinical encounters per 1.0 FTE per month was 70. Conclusions: The relationships between PPC billing provider productivity and clinical workload are complex and vary widely among a convenience sample of academic PPC programs. Given the high burnout rates in the field, efforts should be made to more clearly define these relationships to promote sustainability of both billing and nonbilling PPC providers.


Neutralizing antibodies to human rhinovirus produced in laboratory animals and humans that recognize a linear sequence from VP2.
Synthetic peptides representing amino acids 156 to 170 of virus capsid protein VP2 from human rhinovirus (HRV) type 2 have previously been used to elicit a neutralizing antibody response; polyclonal antisera against this peptide have been compared with a virus-neutralizing monoclonal antibody (8F5) which recognizes the same linear sequence. The neutralizing activity of both antibodies against virus is abolished by an amino acid substitution in VP2 at position 163 but only the peptide antiserum neutralizing activity is affected by a change in VP2 at position 158. The minimal binding site of 8F5 has been mapped, using overlapping peptides, to a sequence TRLNPD covering VP2 residues 160 to 165. Using affinity purification it has been shown that 8 to 10% of total neutralizing activity of polyclonal rabbit or guinea-pig antivirus antiserum is due to recognition of this linear VP2 156 to 170 determinant. Furthermore, a similar population of neutralizing antibodies appears to be associated with an immune response to recent HRV infection in humans. These results confirm the existence of linear determinants on the surface of HRV which may be mimicked by suitable synthetic peptides.


Does children's screen time predict requests for advertised products? Cross-sectional and prospective analyses.
To examine children's screen media exposure and requests for advertised toys and food/drinks. Prospective cohort study. Twelve elementary schools in northern California. Eight hundred twenty-seven third grade children participated at baseline; 386 students in 6 schools were followed up for 20 months. None. Child self-reported requests for advertised toys and foods/drinks. At baseline, children's screen media time was significantly associated with concurrent requests for advertised toys (Spearman r = 0.15 [TV viewing] and r = 0.20 [total screen time]; both P<.001) and foods/drinks (Spearman r = 0.16 [TV viewing] and r = 0.18 [total screen time]; both P<.001). In prospective analysis, children's screen media time at baseline was significantly associated with their mean number of toy requests 7 to 20 months later (Spearman r = 0.21 [TV viewing] and r = 0.24 [total screen time]; both P<.001) and foods/drinks requests (Spearman r = 0.14 [TV viewing] and r = 0.16 [total screen time]; both P<.01). After adjusting for baseline requests and sociodemographic variables, the relationship between screen media exposure and future requests for advertised foods/drinks remained significant for total TV viewing and total screen media exposure. The relationship with future requests for toys remained significant for total screen media exposure. Screen media exposure is a prospective risk factor for children's requests for advertised products. Future experimental studies on children's health- and consumer-related outcomes are warranted.