The hazards of surgery in the obese.
Obesity is an additional risk factor in surgical patients. The mortality rate in obese patients is high (3.6% in my series) and the morbidity is much higher. These patients may be prediabetic, diabetic, hypertensive or atherosclerotic and they are liable to develop postoperative coronary thromboses and chest complications such as acute massive collapse of the lung or bronchopneumonia. In upper abdominal operations, they are more liable to develop septic wounds and postoperative distension. Thrombo-embolic phenomena are more pronte to develop in the obese. Intraoperative bleeding is particularly frequent in obese patients with hypertension, atheroscleroses and fatty liver. Surgery in severe obesity should be limited to emergencies. Elective surgery is not recommended unless it is mandatory, e.g. to reduce weight in hard-core obesity which resists expert medical treatment. Many hard-core obesity cases have psychological problems and require special pre- and postoperative psychological care.


Comparison of uveal melanoma growth rates with mitotic index and mortality.
Between December 1962 and May 1979, growth of choroidal and ciliary body melanomas was documented in 34 patients prior to enucleation, and in one patient whose eye was obtained at autopsy. Melanoma growth rates in 33 of these 35 eyes were calculated and compared with mitotic index, tumor cytology, tumor size, and mortality. Each melanoma appeared to grow at a constant rate that varied widely in different melanomas. Growth rate correlated with mitotic index. Most large tumors and epithelioid and mixed cell melanomas demonstrated fast growth rates. Most melanomas causing death contained epithelioid cells and were growing rapidly. These findings do not support the conclusion of Zimmerman and colleagues that enucleation is responsible for most metastatic deaths. Rather, it argues against one of the fundamental assumptions on which their conclusion is based, namely, that all melanomas have a relatively uniform slow growth rate prior to enucleation.


Evaluation and standardisation of different matrices used for double-blind placebo-controlled food challenges to fish.
Fish allergens represent one of the most common causes of adverse reactions to food worldwide. Double-blind placebo-controlled food challenges (DBPCFC) are the gold standard for food allergy diagnosis. However, no standardised recipes are available for common food allergens such as fish, and a well trained dietitian is essential for creating and standardising them. The present study aimed to create and standardise recipes for use in DBPCFCs to fish. Three recipes were prepared. Employing a standardised procedure, a total of 35 panelists evaluated the different matrices using an evaluation form. A paired comparison test was used to estimate total evaluation's outcome. Fish allergic patients were challenged with different fish species blinded with the selected matrix and evaluated the recipe using the same form. From a base recipe and step-by-step modifications, a low fat recipe was selected among other recipes tested, which proved to be appropriate for fish blinding, in terms of taste, odour, appearance and blinding. Patients challenged with the final matrix found it acceptable, no matter which fish type was used. In this pilot study, a recipe with satisfactory organoleptic characteristics was developed and validated for DBPCFC to fish.


Distribution of angiotensin IV binding sites (AT4 receptor) in the human forebrain, midbrain and pons as visualised by in vitro receptor autoradiography.
Angiotensin IV and other AT4 receptor agonists, improve memory retention and retrieval in the passive avoidance and swim maze learning paradigms. Angiotensin IV binding sites (also known as the AT4 receptors) are widely distributed in guinea pig and monkey (Macaca fascicularis) brains where high densities of the binding sites have been detected in the hippocampus, neocortex and motor nuclei. However, the distribution of the binding sites in the human brain is not known. We have recently localised the angiotensin IV binding sites (AT4 receptors) in post-mortem human brain using iodinated Nle-angiotensin IV, a higher affinity and more stable analogue of angiotensin IV. This radioligand bound with relatively high affinity and specificity to angiotensin IV binding sites. In competition studies on consecutive sections through the prefrontal cortex and claustrum, angiotensin IV, Nle-angiotensin IV and LVV-hemorphin 7 competed for the binding of 125I[Nle]-angiotensin IV with nanomolar affinities. Angiotensin II and the AT1 and AT2 receptor antagonists were ineffective in competing for the binding at concentrations of up to 10 microM. We found high densities of 125I[Nle]-angiotensin IV binding sites throughout the cerebral cortex including the insular, entorhinal, prefrontal and cingulate cortices. Very high densities of the binding sites were observed in the claustrum, choroid plexus, hippocampus and pontine nucleus. Some thalamic nuclei displayed high densities of binding including the anteroprincipal, ventroanterior, anteromedial, medial dorsal and ventrolateral nuclei. The caudate nucleus, putamen, many amygdaloid nuclei and the red nucleus all displayed moderate densities of binding with a higher level detected in the substantia nigra pars compacta. In the hypothalamus, high densities binding sites were found in the ventromedial nucleus with lower levels in the dorsomedial and paraventricular nuclei. The distribution of 125I[Nle]-angiotensin IV binding sites in the human brain is similar to that found in other species and supports multiple roles for the binding sites in the central nervous system, including facilitation of memory retention and retrieval.


[Distribution of radioactivity in subcellular fractions of genital tract tissue and skeletal muscles of guinea pig embryos after administration of 1 alpha,2 alpha-3H(n) testosterone in vitro].
The dynamics of radioactivity in subcellular fractions of the reproductive system and muscle has been studied in the guinea pig embryos from the 21st day of development till birth after the preincubation in a medium containing 1 alpha,2 alpha-3H(n) testosterone (T-3H). The total uptake of T-3H per mg tissue is higher in the reproductive system than in the muscle and attains the highest values during the period of differentiation of target organs by the male type (30-33 days). The nucleocytoplasmic ratio of radioactivity is shifted towards its increase in the nucleus with maximum on the 41st-45th days and by the moment of birth. Radioactivity in the microsomal fraction is higher than in the cytosol (soluble proteins). From the 27th day of development on, when the hormone uptake becomes selective, the radioactivity in the cytosol from the reproductive organs is higher than in the muscle tissue. The data obtained suggest the importance of processes in microsomes for differentiation and organogenesis of reproductive system.


Late infra-renal aortic graft infection: a fearsome complication.
Since the 1950s, aortic graft infections (AGIs) constitute one of the most feared complications after reconstructive vascular surgery. This complication is not frequent, ranging from 1% to 2% in the recently reported series; however, the high rate of death and morbidity after therapeutic attempts justifies its dreadful fame. The majority of cases occur during the first month after surgery. Staphylococcus aureus is the cause of 70% of the early infection cases. Late infections, on the other hand, are even rarer, showing a strong relationship with low virulence microorganisms, where Staphylococcus epidermidis is the main cause. Gram-negative bacteria are also observed in late infections, mainly when an aortic or graft enteric fistula is present. Treatment modalities are plenty, but still debatable. The authors report a case of a woman who was operated on 6 years ago for a reconstructive aortic aneurysm with the implantation of an infrarenal Dacron graft in the aorto bifemoral position. She looked for medical assistance with a 2-month history of weight loss, abdominal/back pain, and fever. Her clinical status rapidly deteriorated. A computed tomography of the abdomen disclosed the diagnosis of an AGI. The patient was promptly treated with antibiotics. Surgery was undertaken to explant the infected graft and another graft was placed into the axillobifemoral position. Culture from the infections site was negative. After surgery the patient quickly developed refractory septic shock and died immediately post-operatively.


[Predictive factors for readmission in heart failure patients].
Heart failure (HF) is a prevalent and increasing disease and represents one of the main causes of hospital admission. It is associated with an important morbi-mortality and a high rate of readmission. The objective of this study was to know the clinical characteristics of admitted patients with HF and to detect any valuable prognosis factors. Prospective study of admitted HF patients between May'99 and May'00. Readmission rate was evaluated six months later. 204 patients were included with an average age of 78 (9.9) years. 66% were women. Diabetes mellitus (DM) (36.4%) and chronic obstructive pulmonary disease (COPD) (23.4%) were the most outstanding associated pathologies. Ischemic heart disease (IHD) was the most frequent etiology in 33.4% cases. Mean time of admission was 10 days. 34% patients had systolic dysfunction (SD). Men with IHD presented a higher rate of SD (p < 0.001). Mortality was 12.4%, especially in COPD patients (p < 0.011). IECAs were prescribed in 71.2% in the SD group. Readmission rate at 6 months was about 43%. Patients with renal failure (p < 0.04) and those with a more impaired functional class (p < 0.02) displayed a higher readmission rate. Several clinical factors determine the morbi-mortality and prognosis including an older age, associated comorbility, type of cardiopathy and presence of systolic dysfunction. All these factors are detected at the time of hospital admission.


Facile decoration of Au nanoparticles on CdS nanorods by polyoxometalate with enhanced photocatalytic activities toward hydrogen evolution.
The tri-component hybrid CdS nanorods (NRs)/Au nanoparticles (NPs)@polyoxometalate (POM) was successfully prepared by a facile, efficient and green method. The structural properties and component analysis were studied by Transmission electron microscopy (TEM), X-ray Diffraction (XRD) and UV-Vis spectra. The POMs sever as not only reductant and bridge molecules, but also as co-catalyst to play an important role in the photocatalytic process. The as-prepared nanohybrid shows obviously enhanced photocatalytic activity toward photocatalytic evolution of hydrogen.


Treatment of Endometrial Cancer in Association with Pelvic Organ Prolapse.
Background. Uterine malignancy coexistent with pelvic organ prolapse (POP) is uncommon and standardized treatment is not established. The objective of this case study was to highlight the management of endometrial cancer in association with pelvic organ prolapse. Case Report. An 87-year-old woman presented with POP Stage IV combined with endometrioid adenocarcinoma of the uterus: clinical Stage IV B. She had multiple medical conditions including stroke, deep vein thrombosis, and pulmonary embolism. She was treated with radiotherapy and pessary was placed. Conclusion. Genital prolapse with abnormal uterine bleeding requires proper evaluation and management. Concurrent adenocarcinoma and POP can be a difficult clinical situation to treat, and optimum management is controversial.


Killer Apps: Developing Novel Applications That Enhance Team Coordination, Communication, and Effectiveness.
As part of the Lorentz workshop, "Interdisciplinary Insights into Group and Team Dynamics," held in Leiden, Netherlands, this article describes how Geeks and Groupies (computer and social scientists) may benefit from interdisciplinary collaboration toward the development of killer apps in team contexts that are meaningful and challenging for both. First, we discuss interaction processes during team meetings as a research topic for both Groupies and Geeks. Second, we highlight teamwork in health care settings as an interdisciplinary research challenge. Third, we discuss how an automated solution for optimal team design could benefit team effectiveness and feed into team-based interventions. Fourth, we discuss team collaboration in massive open online courses as a challenge for both Geeks and Groupies. We argue for the necessary integration of social and computational research insights and approaches. In the hope of inspiring future interdisciplinary collaborations, we develop criteria for evaluating killer apps-including the four proposed here-and discuss future research challenges and opportunities that potentially derive from these developments.


Ascl1 (Mash1) lineage cells contribute to discrete cell populations in CNS architecture.
Ascl1 (previously Mash1) is a bHLH transcription factor essential for neuronal differentiation and specification in the nervous system. Although it has been studied for its role in several neural lineages, the full complement of lineages arising from Ascl1 progenitor cells remains unknown. Using an inducible Cre-flox genetic fate-mapping strategy, Ascl1 lineages were determined throughout the brain. Ascl1 is present in proliferating progenitor cells but these cells are actively differentiating as evidenced by rapid migration out of germinal zones. Ascl1 lineage cells contribute to distinct cell types in each major brain division: the forebrain including the cerebral cortex, olfactory bulb, hippocampus, striatum, hypothalamus, and thalamic nuclei, the midbrain including superior and inferior colliculi, and the hindbrain including Purkinje and deep cerebellar nuclei cells and cells in the trigeminal sensory system. Ascl1 progenitor cells at early stages in each CNS region preferentially become neurons, and at late stages they become oligodendrocytes. In conclusion, Ascl1-expressing progenitor cells in the brain give rise to multiple, but not all, neuronal subtypes and oligodendrocytes depending on the temporal and spatial context, consistent with a broad role in neural differentiation with some subtype specification.


Differential protein expression between normal, early-stage, and late-stage myxomatous mitral valves from dogs.
Valvular heart disease accounts for over 20 000 deaths and 90 000 hospitalizations yearly in the United States. Myxomatous valve disease (MVD) is the most common disease of the mitral valve in humans and dogs. MVD is pathologically identical in these species and its pathogenesis is poorly understood. The objectives of this study were to (i) develop proteomic methodology suitable for analysis of extracellular matrix-rich heart valve tissues and (ii) survey over- and under-expressed proteins that could provide mechanistic clues into the pathogenesis of MVD. Normal, early-stage, and late-stage myxomatous mitral valves from dogs were studied. A shotgun proteomic analysis was used to quantify differential protein expression. Proteins were classified by function and clustered according to differential expression patterns. More than 300 proteins, with 117 of those being differentially expressed, were identified. Hierarchical sample clustering of differential protein profiles showed that early- and late-stage valves were closely related. This finding suggests that proteome changes occur in early degeneration stages and these persist in late stages, characterizing a diseased proteome that is distinct from normal. Shotgun proteome analysis of matrix-rich canine heart valves is feasible, and should be applicable to human heart valves. This study provides a basis for future investigations into the pathogenesis of MVD.


Preparation of artificial antigen and egg yolk-derived immunoglobulin (IgY) of florfenicol amine for ELISA assay.
To investigate the feasibility of IgY technology for the immune detection of haptens, a specific egg yolk antibody (IgY) has been developed in order to detect the florfenicol amine (FFA) residues. FFA was conjugated to bovine serum albumin (BSA) by glutaraldehyde (GA) and the conjugate was used to immunize laying chickens. Anti-FFA IgY antibody was purified by PEG-6000 precipitation and identified by SDS-PAGE. The titer of anti-FFA IgY antibody reached a peak of 1:128,000 after three booster injections. Checkerboard titration showed that a 1:800 dilution of anti-FFA IgY could give an optical density (OD) at around 1.0 at 10 μg/mL FFA-OVA coating concentration. An indirect competitive enzyme-linked immunosorbent assay (icELISA) using specific anti-FFA IgY showed that the IC50 value of anti-FFA IgY was 12.30 ng/mL and the regression curve equation was y = -13.71x + 64.95 (R (2) = 0.945). The strategy of developing anti-hapten IgY antibody is that it may be further used as a new reagent for an immunoassay of hapten residues.


Phenotype of arylsulfatase A-deficient mice: relationship to human metachromatic leukodystrophy.
Metachromatic leukodystrophy is a lysosomal sphingolipid storage disorder caused by the deficiency of arylsulfatase A. The disease is characterized by progressive demyelination, causing various neurologic symptoms. Since no naturally occurring animal model of the disease is available, we have generated arylsulfatase A-deficient mice. Deficient animals store the sphingolipid cerebroside-3-sulfate in various neuronal and nonneuronal tissues. The storage pattern is comparable to that of affected humans, but gross defects of white matter were not observed up to the age of 2 years. A reduction of axonal cross-sectional area and an astrogliosis were observed in 1-year-old mice; activation of microglia started at 1 year and was generalized at 2 years. Purkinje cell dendrites show an altered morphology. In the acoustic ganglion numbers of neurons and myelinated fibers are severely decreased, which is accompanied by a loss of brainstem auditory-evoked potentials. Neurologic examination reveals significant impairment of neuromotor coordination.


Infertility and Identity: A Closer Look Into Experiences of Emerging Young Adult Childhood Cancer Survivors.
Objective: While medical advances are enabling more children with cancer to live into adulthood, a large majority of them suffer from the late effects of treatment and about 30% experience infertility. Infertility impacts both male and female survivors complicating typical development for emerging young adults (EYAs) who typically spend this developmental period actively constructing their identities related to family and gender roles, attaining professional skills, and establishing social views. As literature is limited on identity formation and coping with infertility in young survivors, this study aimed to understand the experiences of childhood cancer survivors who are faced with infertility as a late treatment effect while reconstructing their identity. Method: A qualitative descriptive approach was used to explore the experiences and effects of childhood cancer complications on the identity development of six emerging adults (ages 18-29). Guided by the theoretical framework of identity development data were collected using semistructured interviews. Results: Four distinct themes emerged after the data analyses: restricted exploration and uncertain future, challenges to intimacy and communication, restructuring identity through redefining roles, and coping through familial support. Conclusions: Findings indicate that developmental processes of identity formation are complicated by the challenges stemming from infertility and require specific efforts to reconstruct core identity and redefine desired parental roles. Experimentation and self-discovery may be restricted for EYA cancer survivors as they reevaluate their views on intimate relationships, communication, potential professional roles, and family composition. Practical recommendations for multidisciplinary team members to support this growing population are discussed.


The mammographer's role in addressing special needs.
Many mammography patients have special needs related to their age, sex, surgical status or a physical or mental condition. This article describes some of the accommodations mammographers can make to ensure excellent imaging and quality care for their patients with special needs.


[Organic neuroses as psychosomatic problem].
To study a role of psychogenic and somatogenic factors in the development of organic neuroses, 302 patients were examined: 199 with cardioneurosis and 103 with irritable-bowel syndrome (IBS) with mental and subclinical somatic pathology or without it. Two types of organic neuroses were distinguished: a conversive one--somatized hysteria (psychogenically determined subsyndromal hysterohypochondriac phobic or affective reactions with clear difference of algesic and autonomic disorders from symptoms of the somatic pathology, with polymorphism of the involved organic systems); and autonomic neurosis that is a central link in the structure of psychosomatic correlations, which, on the one hand, was overdone by clinical manifestations of the somatic pathology (mitral prolapse--35%, ventricular extrasystoles--12%, etc. in cardioneurosis, lymphoid hyperplasia of colonic mucosa--100%, dysbiopsis--10%, etc. in IBS); on the other hand, autonomic neurosis is a somatopsychic component of psychopathologic disorders of anxious-phobic, affective and hypochondriac sphere (panic disorder--59%, generalized anxiety--15%, anxious depression--18% in cardioneurosis, melancholic or hypochondriac cyclothymic depressions--76%, hypochondriac development--24% in IBS). Psychosomatic correlations were considered in autonomic neurosis in the context of some continuum, where somatic disorders amplified by functional disorders are on the one pole and true mental pathology including somatoautonomic disorders--on the other pole. Recommendations have been formulated on therapy of organic neuroses with anxiolytics, antidepressants and atypical neuroleptics in combination with somatotropic drugs.


Mapping quantitative trait loci in a non-equilibrium population.
The genetic control of a complex trait can be studied by testing and mapping the genotypes of the underlying quantitative trait loci (QTLs) through their associations with observable marker genotypes. All existing statistical methods for QTL mapping assume an equilibrium population, allowing marker-QTL associations to be simply described at the gametic level. However, many mapping populations in practice may deviate from equilibrium; thus, gametic associations cannot reflect marker-QTL associations at the genotype level. We develop a robust model for mapping QTLs in a non-equilibrium natural population in which individuals are not necessarily randomly mating due to various evolutionary forces. Without use of Hardy-Weinberg equilibrium, the new model founds marker-QTL associations directly on the genotypes, specified by a group of disequilibrium parameters. Simulation studies were performed to test the statistical properties of the model, which suggests that the new model covers current mapping models and can be safely used for any data set.


Reference intervals for reticulocyte indices, immature reticulocyte fraction, and the percentage of hypochromic red blood cells in adult large breed dogs using the ADVIA 2120 hematology analyzer.
Reticulocyte indices are used to characterize anemia, including the identification of regeneration. In people, the immature reticulocyte fraction (IRF), percentage of hypochromic red blood cells (%HYPO-RBC), and other reticulocyte indices have been used as earlier indicators of erythropoiesis and as valuable monitoring tools in the assessment of various therapies. The reference intervals (RI) of the IRF and %HYPO-RBC have not been reported in dogs. The objective of this study was to establish RIs for novel variables (IRF, %HYPO-RBC, and CH-delta) and assess RIs for more commonly reported reticulocyte indices in healthy dogs. RIs were calculated from blood results retrospectively collected from 106 client-owned healthy dogs at the time of induction into a blood donor program using the ADVIA 2120 hematology analyzer (Siemens Healthcare Diagnostics). For the calculation of RIs, appropriate tests were applied for outlier detection and normality assessment. For variables normally distributed, RIs and their respective 90% confidence intervals (CIs) were calculated using parametric methods, while for variables not normally distributed, robust methods were used and bootstrapping for calculating the 90% CIs. The following RIs were established: reticulocyte hemoglobin content (CHr) 24.5-28 pg, mean reticulocyte volume (MCVr) 85.9-99.3 fL, mean corpuscular hemoglobin concentration of reticulocytes (CHCMr) 271.0-306.3 g/L, IRF 10.4%-43.5%, CH-delta 0.5-4.3 pg, and percentage of hypochromic red blood cells (%HYPO-RBC) 0.10%-0.80%. The results of this study provide RIs for novel reticulocyte variables. Further studies are required to determine the clinical utility of IRF, %HYPO-RBC, and CH delta as early indicators of erythropoietic activity in canine patients.


Evaluating the ability of different characterization parameters to describe the surface of fried foods.
The objective of this work is to identify surface topography characterization parameters that are capable of discriminating the surfaces of different fried foods. Three fried food model systems with clearly different surfaces were formulated from vital wheat gluten, native wheat starch, and potato flakes. The surfaces were measured with a scanning laser microscope (SLM), and the ability of several parameters to discriminate between them was tested. Two conventional parameters, the root mean square roughness (Sq) and the surface Kurtosis (Sku), were calculated, along with parameters derived from area-scale fractal analysis: smooth-rough crossover (SRC), fractal dimension, and relative area as a function of scale. The coefficient of variation (COV) of Sq, Sku, and SRC and fractal dimension of different sizes of measurement regions were calculated for the surface of the roughest product in order to specify a measurement region that would be sufficiently large to be representative. The size of the representative region was found to be 25 mm². Among the parameters evaluated in this study, the most reliable parameter for discriminating the surfaces of fried foods is the relative area calculated from area-scale fractal analysis.


Antiresorptive Drugs and the Risk of Femoral Shaft Fracture in Men and Women With Osteoporosis: A Cohort Study Using the National Database of Health Insurance Claims of Japan.
This cohort study aimed to estimate incidence rates of femoral shaft fracture in patients who were treated with antiresorptive drugs. We used data from the National Database of Health Insurance Claims of Japan from April 2009 and October 2016. All patients with new use of an antiresorptive drug, prescription-free period of ≥3 months, and no prior femoral fractures were included. Femoral shaft fractures were identified using a validated definition based on International Classification of Diseases, 10th revision (ICD-10) codes. Incidence rate ratios were estimated using Poisson regression, with adjustment for sex, age, and the Charlson Comorbidity Index. We identified 7,958,655 patients (women: 88.4%; age ≥75 years: 51.2%). Femoral shaft fractures were identified in 22,604 patients. Incidence rates per 100,000 person-years were 74.8 for women, 30.1 for men, 30.1 for patients aged ≤64 years, 47.7 for patients aged 65-74 years, and 99.0 for patients aged ≥75 years. Adjusted incidence rate ratios in patients taking versus not taking each type of antiresorptive drug were 1.00 (95% confidence interval [CI], 0.98-1.03) for bisphosphonates, 0.46 (95% CI, 0.44-0.48) for selective estrogen receptor modulators, 0.24 (95% CI, 0.18-0.32) for estrogens, 0.75 (95% CI, 0.71-0.79) for calcitonins, and 0.93 (95% CI, 0.84-1.03) for denosumab. The adjusted incidence rate ratio for alendronate was 1.18 (95% CI, 1.14-1.22). The incidence rates of femoral shaft fracture varied across patients treated with different antiresorptive drugs. Further research on a specific antiresorptive drug can increase understanding of the risk of femoral shaft fracture.


Evidence of adaptability in metal coordination geometry and active-site loop conformation among B1 metallo-beta-lactamases .
Subclass B1 beta-lactamases are Zn(II)-dependent hydrolases that confer bacterial resistance to most clinically useful beta-lactam antibiotics. The enzyme BcII from Bacillus cereus is a prototypical enzyme that belongs to this group, the first Zn(II)-dependent beta-lactamase to be discovered. Crucial aspects of the BcII catalytic mechanism and metal binding mode have been assessed mostly on the Co(II)-substituted surrogate. Here we report a high-resolution structure of Co(II)-BcII, revealing a metal coordination geometry identical to that of the native zinc enzyme. In addition, a high-resolution structure of the apoenzyme, together with structures with different degrees of metal occupancy and oxidation levels of a conserved Cys ligand, discloses a considerable mobility of two loops containing four metal ligands (namely, regions His116-Arg121 and Gly219-Cys221). This flexibility is expected to assist in the structural rearrangement of the metal sites during catalytic turnover, which, along with the coordination geometry adaptability of Zn(II) ions, grants the interaction with a variety of substrates, a characteristic feature of B1 metallo-beta-lactamases.


Care-Partner Support and Hospitalization in Assisted Living During Transitional Home Health Care.
Care-partner support affects outcomes among assisted living (AL) residents. Yet, little is known about care-partner support and its effects on hospitalization during post-acute care transitions. This study examined the variation in care-partner support and its impact on hospitalizations among AL residents receiving Medicare home health (HH) services. Analysis of national data from the Outcome and Assessment Information Set, Medicare claims, Area Health Resources File, and the Social Deprivation Index File. AL facilities and Medicare HH agencies in the United States. 741,926 Medicare HH admissions of AL residents in 2017. Care-partner support during the HH admission was measured based on the type and frequency of assistance from AL staff in seven domains (i.e., activities of daily living (ADL), instrumental ADLs, medication administration, treatment, medical equipment, home safety, and transportation). Care-partner support in each domain was measured as "assistance not needed" (reference group), "Care-partner currently provides assistance," "care-partner need additional training/support to provide assistance" (i.e., inadequate care-partner support), and "care-partner unavailable/unlikely to provide assistance" (i.e., unavailable care-partner support). Outcome was time-to-hospitalization during the HH admission. Among the 741,926 Medicare HH admissions of AL residents, inadequate care-partner support was identified for all seven domains that ranged from 13.1% (for transportation) to 49.8% (for treatment), and care-partner support was unavailable from 0.9% (for transportation) to 11.0% (for treatment). In Cox proportional hazard models adjusted for patient covariates and geography, compared with "assistance not needed", having inadequate and unavailable care-partner support was related to increased risk of hospitalization by 8.9% (treatment (hazard ratio (HR) =1.089, P < .001)) to 41.3% (medication administration (HR =1.413, P < .001)). For AL residents receiving HH services, having less care-partner support was related to increased risk of hospitalization, particularly regarding medication administration, medical equipment, and transportation/advocacy.


Adolescent smokers seen in general practice: health, lifestyle, physical measurements, and response to antismoking advice.
To compare physical, lifestyle, and health characteristics of adolescent smokers and non-smokers and their initial response to anti-smoking counselling. Adolescents aged 13, 15, and 17 years were identified from age-sex registers and invited by letter for a general practice health check. Three general practices in the MRC general practice research framework. Blood pressure, body mass index, saliva cotinine concentration, peak flow rate, alcohol consumption, exercise, duration of sleep, and stated persistent health problems. 73% of the adolescents (491) attended for the health check. A total of 68 (14%) were regular smokers. By age 17 those who smoked regularly had a significantly lower systolic blood pressure than those who had never smoked regularly (by 6 mm Hg; p = 0.025) despite a significantly higher body mass index (by 1.5; p <0.001) [corrected]. Cotinine concentrations increased with smoking exposure, from 0.7 ng/ml when no family member smoked to 155 ng/ml in active smokers of six or more cigarettes a week. Significantly more regular smokers than never regular smokers drank greater than or equal to 8 g alcohol a day (chi 2 = 15.2 adjusted for age and sex p less than 0.001); regular smokers exercised less (1.0 hrs/week in boys and 0.8 hrs/week in girls v 3.4 hrs/week in boys and 2.2 hrs/week in girls; p less than 0.001) and slept less (8.0 hrs/night v 8.5 hrs/night at age 17; p less than 0.005). Persistent health problems, mostly asthma or allergic symptoms, were reported by 25% (17/68) of the smokers and 16% (60/381) of the non-smokers. Of the smokers given counselling, 60% (26/43) made an agreement with the practice doctor or nurse to give up smoking. General practice is an appropriate setting for adolescents to receive advice on healthy lifestyle, which should not focus solely on smoking.


High-intensity Interval Training in the Boundaries of the Severe Domain: Effects on Sprint and Endurance Performance.
In order to compare the effects of two 4-week interval training programs performed at the lower (Critical Power, CP) or at the higher (The highest intensity at which V˙O2max is attained, IHIGH) intensities of the severe exercise domain on sprint and endurance cycling performance, 21 recreationally trained cyclists performed the Wingate Anaerobic Test (WAnT) and a 250-kJ time trial. Accumulated oxygen deficit (AOD), surface electromyography (RMS), and blood lactate kinetics were measured during the WAnT. Subjects were assigned to 105% CP or IHIGH groups. During the WAnT, significantly greater improvements in peak (Mean ±95%CI) (5.7±2.3% vs. 0.2±2.2%), mean power output (MPO) (3.7±2.0% vs. 0.5±1.8%), and RMS (17.8±7.4% vs. -15.7±7.9%) were observed in the IHIGH group (P<0.05). Higher and lower AOD, respectively, at the start and during the second half of the WAnT were observed after IHIGH training. The changes in RMS and MPO induced by the training were significantly correlated (r=0.584). The 2 interventions induced improvements in the 250-kJ time trial. In conclusion, although the improvements in endurance performance were similar, training at IHIGH led to higher gains in WAnT performance than training at 105%CP.


Current trends of sentinel lymph node biopsy for breast cancer--a surgeon's perspective.
Sentinel lymph node biopsy (SLNB) is standard care for patients with early-stage breast cancer, and axillary lymph node dissection (ALND) is considered unnecessary when sentinel lymph nodes (SLNs) are tumor-free. Additional non-SLN metastasis in patients with positive SLNs can be estimated using several risk factors such as primary tumor size, metastatic tumor size in SLNs, lymphatic vessel invasion, and so on. All patients with positive SLNs may be treated with further ALND based on their own risk for non-SLN metastasis. Recent randomized clinical trials have already proved less surgical morbidity and better QOL for SLNB alone compared with ALND. However, trials concerning the efficacy of ALND in positive SLNB patients in preventing local regional recurrence and improving overall survival compared with no ALND, and also, concerning the effectiveness of ALND compared with axillary radiation therapy (RT), have not yielded clear results. The prognostic significance of micrometastasis in SLNs or bone marrow also remains to be determined. So far SLNB is not acceptable for patients with positive nodes in the axilla at initial diagnosis even if their axillary metastases are down-staged to negative by neoadjuvant chemotherapy. Although basically SLNB does not need to be performed for patients with pure ductal carcinoma in situ (DCIS), it is recommended for patients with an initial diagnosis of DCIS which is large, palpable, high grade, or found in younger patients. Because these types of DCIS have higher incidences of accompanying invasive lesions. In addition if patients will undergo mastectomy, SLNB is recommended because of the inability to perform SLNB after mastectomy. SLNB may be acceptable for patients with T3 or T4b tumors, even though SLN identification is lower yet SLN involvement is higher compared with T1 or T2 tumors, and systemic adjuvant therapy is more important for patients with T3 or T4b tumors. SLNB is a bridge to further axillary treatment such as ALND or axillary RT, and which strategy, including no further treatment, is best considered individually based on recurrence risk, treatment responsiveness and use or non-use of systemic therapy.


Hepatic insensitivity to glucagon in ob/ob mice.
Hepatic cAMP concentration of normal mice increased 40 fold within 10 min after a single dose of glucagon (2 mg/kg, IP). In contrast, hepatic cAMP increased only 2 fold in ob/ob mice. Glucagon induced hepatic L-phenylalanine:pyruvate aminotransferase and stimulated glycogenolysis in normal mice but failed to elicit these cAMP-mediated responses in ob/ob mice. The insensitivity of ob/ob mice to glucagon was not ameliorated by fasting or by theophylline.


Global nutrition research: nutrition and breast cancer prevention as a model.
The gene-environment interaction is paramount in light of the worldwide rise in incidence of chronic diseases, with cancers in the pole position. Diet is an environmental factor with potential to influence cancer onset by shaping the epigenome (i.e., the genome organization that controls the differential expression of genes). Yet, there is no consensus regarding how diet might help prevent breast cancer, the second most frequent malignancy globally. The complexity of breast cancers requires working on a global and multidisciplinary scale to further understand the relationship between breast cancer type, diet, and the epigenome. This article describes the International Breast Cancer & Nutrition collaboration as one such approach. A global endeavor brings the diversity necessary to pinpoint important diet-gene relationships. Being developed are models, detection and assessment tools, and funding and public policy frameworks necessary to advance primary prevention research for the benefit of all populations affected by breast cancer. This paradigm can be adapted to understanding diet-gene relationships for other chronic diseases.


A missense variant in NCF1 is associated with susceptibility to multiple autoimmune diseases.
Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with a strong genetic component characterized by autoantibody production and a type I interferon signature. Here we report a missense variant (g.74779296G>A; p.Arg90His) in NCF1, encoding the p47phox subunit of the phagocyte NADPH oxidase (NOX2), as the putative underlying causal variant that drives a strong SLE-associated signal detected by the Immunochip in the GTF2IRD1-GTF2I region at 7q11.23 with a complex genomic structure. We show that the p.Arg90His substitution, which is reported to cause reduced reactive oxygen species (ROS) production, predisposes to SLE (odds ratio (OR) = 3.47 in Asians (Pmeta = 3.1 × 10-104), OR = 2.61 in European Americans, OR = 2.02 in African Americans) and other autoimmune diseases, including primary Sjögren's syndrome (OR = 2.45 in Chinese, OR = 2.35 in European Americans) and rheumatoid arthritis (OR = 1.65 in Koreans). Additionally, decreased and increased copy numbers of NCF1 predispose to and protect against SLE, respectively. Our data highlight the pathogenic role of reduced NOX2-derived ROS levels in autoimmune diseases.


Measuring scatter radiation in diagnostic X rays for radiation protection purposes.
During the last decades, radiation protection and dosimetry in medical X-ray imaging practice has been extensively studied. The purpose of this study was to measure secondary radiation in a conventional radiographic room, in terms of ambient dose rate equivalent H*(10) and its dependence on the radiographic exposure parameters such as X-ray tube voltage, tube current and distance. With some exceptions, the results indicated that the scattered radiation was uniform in the space around the water cylindrical phantom. The results also showed that the tube voltage and filtration affect the dose rate due to the scatter radiation. Finally, the scattered X-ray energy distribution was experimentally calculated.


Rapid Detection of SARS-CoV-2 RNA in Human Nasopharyngeal Specimens Using Surface-Enhanced Raman Spectroscopy and Deep Learning Algorithms.
A rapid and cost-effective method to detect the infection of SARS-CoV-2 is fundamental to mitigating the current COVID-19 pandemic. Herein, a surface-enhanced Raman spectroscopy (SERS) sensor with a deep learning algorithm has been developed for the rapid detection of SARS-CoV-2 RNA in human nasopharyngeal swab (HNS) specimens. The SERS sensor was prepared using a silver nanorod array (AgNR) substrate by assembling DNA probes to capture SARS-CoV-2 RNA. The SERS spectra of HNS specimens were collected after RNA hybridization, and the corresponding SERS peaks were identified. The RNA detection range was determined to be 103-109 copies/mL in saline sodium citrate buffer. A recurrent neural network (RNN)-based deep learning model was developed to classify 40 positive and 120 negative specimens with an overall accuracy of 98.9%. For the blind test of 72 specimens, the RNN model gave a 97.2% accuracy prediction for positive specimens and a 100% accuracy for negative specimens. All the detections were performed in 25 min. These results suggest that the DNA-functionalized AgNR array SERS sensor combined with a deep learning algorithm could serve as a potential rapid point-of-care COVID-19 diagnostic platform.


The Herpes Simplex Virus Protein pUL31 Escorts Nucleocapsids to Sites of Nuclear Egress, a Process Coordinated by Its N-Terminal Domain.
Progeny capsids of herpesviruses leave the nucleus by budding through the nuclear envelope. Two viral proteins, the membrane protein pUL34 and the nucleo-phosphoprotein pUL31 form the nuclear egress complex that is required for capsid egress out of the nucleus. All pUL31 orthologs are composed of a diverse N-terminal domain with 1 to 3 basic patches and a conserved C-terminal domain. To decipher the functions of the N-terminal domain, we have generated several Herpes simplex virus mutants and show here that the N-terminal domain of pUL31 is essential with basic patches being critical for viral propagation. pUL31 and pUL34 entered the nucleus independently of each other via separate routes and the N-terminal domain of pUL31 was required to prevent their premature interaction in the cytoplasm. Unexpectedly, a classical bipartite nuclear localization signal embedded in this domain was not required for nuclear import of pUL31. In the nucleus, pUL31 associated with the nuclear envelope and newly formed capsids. Viral mutants lacking the N-terminal domain or with its basic patches neutralized still associated with nucleocapsids but were unable to translocate them to the nuclear envelope. Replacing the authentic basic patches with a novel artificial one resulted in HSV1(17+)Lox-UL31-hbpmp1mp2, that was viable but delayed in nuclear egress and compromised in viral production. Thus, while the C-terminal domain of pUL31 is sufficient for the interaction with nucleocapsids, the N-terminal domain was essential for capsid translocation to sites of nuclear egress and a coordinated interaction with pUL34. Our data indicate an orchestrated sequence of events with pUL31 binding to nucleocapsids and escorting them to the inner nuclear envelope. We propose a common mechanism for herpesviral nuclear egress: pUL31 is required for intranuclear translocation of nucleocapsids and subsequent interaction with pUL34 thereby coupling capsid maturation with primary envelopment.


Primary visual cortical thickness in correlation with visual field defects in patients with pituitary macroadenomas: a structural 7-Tesla retinotopic analysis.
Vision loss remains a debilitating complication of pituitary adenomas, although there is considerable variability in visual impairment before and after decompression surgery. Growing evidence suggests secondary damage to remote visual structures may contribute to vision loss in patients with chiasmatic compression. The present study leverages ultrahigh field 7-T MRI to study the retinotopic organization of the primary visual cortex (V1), and correlates visual defects with cortical thinning in V1 to characterize consequences of pituitary adenomas on the posterior visual system. Eight patients (4 males and 4 females, mean age 44.3 years) with pituitary adenomas who exhibited chiasmatic compression and visual field defects, as well as 8 matched healthy controls (4 males and 4 females, mean age 43.3 years), were scanned at 7-T MRI for this prospective study. Whole-brain cortical thickness was calculated using an automated algorithm. A previously published surface-based algorithm was applied to associate the eccentricity and polar angle with each position in V1. Cortical thickness was calculated at each point in the retinotopic organization, and a cortical thickness ratio was generated against matched controls for each point in the visual fields. Patients with adenoma additionally underwent neuroophthalmological examination including 24-2 Humphrey automated visual field perimetry. Pattern deviation (PD) of each point in the visual field, i.e., the deviation in point detection compared with neurologically healthy controls, was correlated with cortical thickness at corresponding polar and eccentricity angles in V1. Whole-brain cortical thickness was successfully derived for all patients and controls. The mean tumor volume was 19.4 cm3. The median global thickness of V1 did not differ between patients (mean ± SD 2.21 ± 0.12 cm), compared with controls (2.06 ± 0.13 cm, p > 0.05). Surface morphometry-based retinotopic maps revealed that all 8 patients with adenoma showed a significant positive correlation between PD and V1 thickness ratios (r values ranged from 0.31 to 0.53, p < 0.05). Mixed-procedure analysis revealed that PD = -8.0719 + 5.5873*[Median V1 Thickness Ratio]. All 8 patients showed significant positive correlations between V1 thickness and visual defect. These findings provide retinotopic maps of localized V1 cortical neurodegeneration spatially corresponding to impairments in the visual field. These results further characterize changes in the posterior visual pathway associated with chiasmatic compression, and may prove useful in the neuroophthalmological workup for patients with pituitary macroadenoma.


Neovascularization is influenced by androgenic hormones in the tissue implant response.
The objective of this investigation was to demonstrate the effect of androgens on the neovascularization of the fibrous tissue surrounding tricalcium phosphate (TCP) implants. Sixteen animals in four experimental groups (n = 4/group) were implanted with one TCP implant each. Group I animals were implanted with the sham TCP ceramic (Control). Group II animals received a testosterone-loaded ceramic. Group III animals were implanted with a dihydrotestosterone containing bioceramic. Group IV animals received the androstenedione filled bioceramic. At 90 days post-implantation, the fibrous tissue surrounding the implants were evaluated microscopically following staining with routine hematoxylin and eosin (H&E), Masson's trichrome, and Papanicolaou stains. Using Image Pro (Media Cybernetics, Silver Spring, MD) digital analysis software, data were collected to compare the hormonal effects on the number (per high power field) and size of blood vessels (micrometers, µm) within the fibrous tissue surrounding all four groups. The presence of androgens greatly affected the angiogenic response within the fibrous tissue. All three hormones exhibited less neovascularization compared to the control. Though not as dramatic as androstenedione (3±0), both testosterone (12±1) and dihydrotestosterone (10±1) suppressed the number of blood vessels present in the fibrous tissue capsule compared to control (13±1). However, the circumference of the vessels was much larger for the testosterone (236µm ±8µm) and dihydrotestosterone (256µm±4µm) treated groups compared to the androstenedione (146µm ±7µm) or control (163µm±3µm) groups. The results of this study demonstrate androgens strongly vary in their effect on neovascularization by limiting the number of new vessels developed while contributing to the presence of larger vessels within the fibrous tissue surrounding TCP implants loaded with testosterone and dihydrotestosterone.


Developing clinical prediction models for nonrecovery in older patients seeking care for back pain: the back complaints in the elders prospective cohort study.
Back pain is a leading cause of disability worldwide and is common in older adults. No clinical prediction models for poor long-term outcomes have been developed in older patients with back pain. This study aimed to develop and internally validate 3 clinical prediction models for nonrecovery in this population. A prospective cohort study in general practice was conducted (Back Complaints in the Elders, Netherlands), including 675 patients >55 years with a new episode of care for back pain. Three definitions of nonrecovery were used combining 6-month and 12-month follow-up data: (1) persistent back pain, (2) persistent disability, and (3) perceived nonrecovery. Sample size calculation resulted in a maximum of 14 candidate predictors that were selected from back pain prognostic literature and clinical experience. Multivariable logistic regression was used to develop the models (backward selection procedure). Models' performance was evaluated with explained variance (Nagelkerke's R2), calibration (Hosmer-Lemeshow test), and discrimination (area under the curve [AUC]) measures. The models were internally validated in 250 bootstrapped samples to correct for overoptimism. All 3 models displayed good overall performance during development and internal validation (ie, R2 > 30%; AUC > 0.77). The model predicting persistent disability performed best, showing good calibration, discrimination (AUC 0.86, 95% confidence interval 0.83-0.89; optimism-adjusted AUC 0.85), and explained variance (R2 49%, optimism-adjusted R2 46%). Common predictors in all models were: age, chronic duration, disability, a recent back pain episode, and patients' recovery expectations. Spinal morning stiffness and pain during spinal rotation were included in 2 of 3 models. These models should be externally validated before being used in a clinical primary care setting.


11,12 -Epoxyeicosatrienoic acid (11,12 EET) reduces excitability and excitatory transmission in the hippocampus.
Recent studies suggest a role for the arachidonic acid-derived epoxyeicosatrienoic acids (EETs) in attenuating epileptic seizures. However, their effect on neurotransmission has never been investigated in detail. Here, we studied how 11,12- and 14,15 EET affect excitability and excitatory neurotransmission in mouse hippocampus. 11,12 EET (2 μM), but not 14,15 EET (2 μM), induced the opening of a hyperpolarizing K+ conductance in CA1 pyramidal cells. This action could be blocked by BaCl2, the G protein blocker GDPβ-S and the GIRK1/4 blocker tertiapin Q and the channel was thus identified as a GIRK channel. The 11,12 EET-mediated opening of this channel significantly reduced excitability of CA1 pyramidal cells, which could not be blocked by the functional antagonist EEZE (10 μM). Furthermore, both 11,12 EET and 14,15 EET reduced glutamate release on CA1 pyramidal cells with 14,15 EET being the less potent regioisomer. In CA1 pyramidal cells, 11,12 EET reduced the amplitude of excitatory postsynaptic currents (EPSCs) by 20% and the slope of field excitatory postsynaptic potentials (fEPSPs) by 50%, presumably via a presynaptic mechanism. EEZE increased both EPSC amplitude and fEPSP slope by 40%, also via a presynaptic mechanism, but failed to block 11,12 EET-mediated reduction of EPSCs and fEPSPs. This strongly suggests the existence of distinct targets for 11,12 EET and EEZE in neurons. In summary, 11,12 EET substantially reduced excitation in CA1 pyramidal cells by inhibiting the release of glutamate and opening a GIRK channel. These findings might explain the therapeutic potential of EETs in reducing epileptiform activity.


Implementation of Patient-Reported Outcomes (PROMs) from specialist pain clinics in England and Wales: Experience from a nationwide study.
Evaluating outcomes in routine clinical practice is a significant challenge for specialist pain clinics due to the complexity of interventions provided and the subjective nature of pain. This study reports findings from implementation of Patient Reported Outcomes (PROMs) in pain clinics in England and Wales between 2011 and 2013. A paper-based questionnaire was administered at a first appointment in participating centres. This assessed quality of life, experience of health care and health care usage with postal follow-up at 6 and 12 months by the research team. Feasibility was assessed in terms of response rates, completion rates and outcomes. Ninety-one (56%) clinics participated, entering 9,588 patients (19% of those eligible). For responders, there was a 92% item completion rate. The dropout rate was high, 46% and 19% returned questions at 6 and 12 months, respectively. Quality of life at baseline was low, with a mean EQ5D-3L Time Trade Off value of 0.32. Amongst responders at 12 months, 92% continued to experience significant pain. For those with planned discharges 30% achieved the Minimal Important Change for quality of life. Nonetheless, 70% reported positive experiences of care. Patients attending UK pain clinics report an extraordinarily poor quality of life and difficulty with understanding their condition. Problems with PROMs implementation included initial recruitment, follow-up response rates, classification systems and benchmarking. Successful implementation should include use of electronic data capture, feedback and focus on gradual improvement. To achieve this would require extended periods of funding. No nationwide evaluation of the effectiveness of specialist pain clinics had previously been attempted. Comparison of patient outcomes from services enables improvement. This work provides a platform to improve methods of routine PROMs capture in pain clinics, measure clinical effectiveness and identify areas for potential research.


Catalytic and chemical competence of regulation of cdc25 phosphatase by oxidation/reduction.
Cdc25 phosphatases belong to the family of protein tyrosine phosphatases (PTPs) that contain an active-site cysteine and form a phosphocysteine intermediate. Recently, oxidation/reduction of active-site cysteines of PTPs, including Cdc25, has been proposed to serve as a form of reversible regulation for this class of enzymes. Here we provide in vitro evidence that supports the chemical and kinetic competence for oxidation/reduction of the active-site cysteines of Cdc25B and Cdc25C as a mechanism of regulation. Using kinetic measurements and mass spectrometry, we have found that the active-site cysteines of the Cdc25's are highly susceptible to oxidation. The rate of thiolate conversion to the sulfenic acid by hydrogen peroxide for Cdc25B is 15-fold and 400-fold faster than that for the protein tyrosine phosphatase PTP1B and the cellular reductant glutathione, respectively. If not for the presence of an adjacent (back-door) cysteine in proximity to the active-site cysteine in the Cdc25's, the sulfenic acid would rapidly oxidize further to the irreversibly inactivated sulfinic acid, as determined by using kinetic partitioning and mass spectrometry with mutants of these back-door cysteines. Thus, the active-site cysteine is protected by rapid intramolecular disulfide formation with the back-door cysteines in the wild-type enzymes. These intramolecular disulfides can then be rapidly and effectively rereduced by thioredoxin/thioredoxin reductase but not glutathione. Thus, the chemistry and kinetics of the active-site cysteines of the Cdc25's support a physiological role for reversible redox-mediated regulation of the Cdc25's, important regulators of the eukaryotic cell cycle.


Improvement of accuracy in digital holography by use of multiple holograms.
Speckle pattern decorrelation reduces the accuracy of interferometric shape and deformation measurements. We introduce a technique for the reduction of speckle noise in digital holography. The method is not based on classical filtering techniques such as median filters. Instead it utilizes the shift theorem of the Fourier transform. For this method several holograms of the same object under test are recorded. The reconstruction leads to a set of object wave fields with different speckle patterns. A proper averaging procedure, taking into account the properties of the wrapped phases, leads to an improvement of the accuracy in the resulting phase difference. The theory of the applied method is described and our first results for technical components with an improvement of accuracy up to 1/57 of the wavelength are presented.


X-ray microanalysis of the mid-gut epithelium of the fruitfly Drosophila melanogaster.
The cells in the mid-gut epithelium of Drosophila melanogaster which accumulate copper were examined by X-ray microanalysis. Both wavelength dispersive and energy dispersive analyses were used. The copper was located in granules o-3-1-o mum in diameter which were bounded by membranes and similar, morphologically, to secondary lysosomes. The copper was associated with high concentrations of sulphur but no other elements with an atomic number greater than 9 (the lower limit of the analysis equipment) were present in appreciable concentrations.


Comparison of personal exposure meter placement for the determination of office worker ELF magnetic field exposures.
This article compares extremely low frequency (ELF) magnetic field exposures measured by placing EMDEX Lite personal exposure meters (PEMs) at the head, chest, and waist level for a group of office workers. Twenty-three volunteers were solicited to wear three PEMs simultaneously; one was attached to a baseball cap worn on the head, one was attached to a band and worn around the neck (positioned on the chest), and one was worn in a belted pouch around the waist (positioned on the right side of the hip). The effect of PEM placement was evaluated by comparing full-shift average exposures and daily maximum or peak exposure. The results of this investigation indicate that time-weighted average magnetic field exposures determined at the hip provide the highest mean exposure estimates. Averages of the full-shift mean magnetic field measurements taken at hip and head levels were statistically greater than measurements taken at the chest level by 33 and 22%, respectively. Comparisons of the maximum or peak magnetic field exposures by body position indicate that the hip position produced an average exposure estimate that was 136% greater than the average head-level measurement. Results suggest that for office workers PEM meter placement on the body does not produce large differences in full-shift average ELF magnetic flux density exposures. However, the hip position produced the largest daily maximum or peak exposures. It is recommended that PEMs be placed on the hip for exposure assessments in office environments, because this placement is the most commonly used, the most convenient, and resulted in the highest magnetic field exposures.


Long-term Outcomes After Proton Beam Irradiation in Patients With Large Choroidal Melanomas.
Although radiotherapy has been used more frequently in past decades for the management of large melanomas, long-term efficacy of proton beam irradiation (PBI) of large choroidal melanomas has not been reported. To evaluate long-term outcomes in patients who underwent PBI for the treatment of large choroidal melanomas. Data were obtained at a single Boston, Massachusetts, academic tertiary referral practice for this retrospective cohort study. In total, 336 patients with large tumors treated over a 13-year period from January 1, 1985, to December 31, 1997, and followed up until the end points were reached or until December 31, 2008, were included. Data analyses were initially completed in February 2017 and finalized in July 2017. Large tumors were those with a height 10 mm or greater or a longest linear diameter greater than 16 mm or a height greater than 8 mm when the optic nerve was involved. Proton beam irradiation (total 70 Gy) delivered in 5 equal fractions. The primary outcomes of rates of visual acuity retention, eye retention, tumor recurrence, and melanoma-related mortality were calculated using Kaplan-Meier estimates, and Cox proportional hazards regression analyses were completed to evaluate risk factors for tumor recurrence and melanoma-related mortality. In this cohort of 336 patients with large tumors, 150 were women and 329 were white; mean (SD) age was 60.0 (14.0) years. Of 178 patients without optic nerve involvement (tumor >1 disc diameter from optic nerve), the mean (SD) largest basal diameter was 18.1 (1.9) mm and mean height was 8.2 (2.7) mm. Optic nerve involvement and tumors greater than 8 mm were observed in 109 patients (32.4% of the cohort). Baseline visual acuity of 20/200 or better was observed in 244 patients (72.6%), and worse than 20/800 in 52 (15.5%). Ten-year rates of visual acuity retention were 8.7% (95% CI, 4.1%-15.6%) for at least 20/200 and 22.4% (95% CI, 15.4%-30.4%) for at least counting fingers. Ten years after PBI therapy, the eye was retained (70.4%; 95% CI, 61.5%-77.6%) and tumor controlled (87.5%; 95% CI, 76.8%-93.5%) in most patients. The 10-year all-cause mortality rate was 60.7% (95% CI, 55.5%-65.9%). Approximately half of the patients died of metastatic uveal melanoma (10-year rate, 48.5%; 95% CI, 43.0%-54.4%). This study demonstrates that eye conservation is possible in most cases, with ambulatory vision retained in a small proportion of patients 10 years after PBI. Tumor recurrence rates were low and mortality rates were comparable to those observed after enucleation.


Classification and Grading of Central Nervous System Tumors According to the World Health Organization 5th Edition.
The World Health Organization (WHO) released the 5th edition of its classification of central nervous system (CNS) tumors in 2021. Advances in the landscape of molecular tumor pathophysiology prompted major revisions to the previous edition released in 2016, some of which were first introduced by the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy-Not Official WHO (cIMPACT-NOW). The 2021 classification system integrates newly gained molecular insights to guide changes in tumor taxonomy and nomenclature, introduces several new types of tumors, and expands the use of molecular testing for diagnosis and grading, with a particular impact on adult-type and pediatric-type gliomas, ependymomas, and embryonal tumors. These updates aim to promote clear and accurate diagnoses, yield more reliable prognostic information, and enable the selection of optimal therapies. Familiarity with these changes will be of great importance for clinicians involved in the management of CNS tumor patients.


Comparisons of the pestivirus bovine viral diarrhoea virus with members of the flaviviridae.
The molecular features of bovine viral diarrhoea virus (BVDV), a member of the Pestivirus genus currently classified in the Togaviridae, were examined for characteristics resembling those of the Flaviviridae family. Like flaviviruses, BVDV possesses a single-stranded RNA genome (approx. 4.3 x 10(6) Mr) deficient in a 3' poly(A) tract. This RNA has a single open reading frame spanning the length of the genome in the viral RNA sense (positive polarity), implying an expression strategy involving the processing of a precursor polyprotein. With the exception of several short but significant stretches of identical amino acids within two non-structural proteins, no extended regions of nucleotide or amino acid sequence homology between BVDV and representatives of three serological subgroups of mosquito-borne flaviviruses were noted. However, comparison of the organization of protein-coding domains along the genomes and the hydropathic profiles of amino acid sequences revealed pronounced similarities. It is proposed that Pestivirus, of which BVDV is the prototype member, should no longer be grouped in the Togaviridae family, but rather be considered a genus of non-arthropod-borne viruses within the Flaviviridae.


In Vitro Evaluation of Antioxidant and Antimicrobial Activities of Melaleuca alternifolia Essential Oil.
The in vitro antioxidant and antimicrobial activity of the essential oil from Melaleuca alternifolia (M. alternifolia) was evaluated in this report. The antioxidant potential of the essential oil from M. alternifolia was evaluated by the DPPH (2,2-diphenyl-1-picrylhydrazyl) method, thiobarbituric acid reactive species (TBARS) assay, and the hydroxyl radical scavenging activity method. The essential oil from M. alternifolia was able to reduce DPPH with an EC50 (concentration for 50% of maximal effect) of 48.35 μg/ml, inhibit the lipid peroxidation with an IC50 (50% inhibitory concentration) of 135.9 μg/ml, and eliminate hydroxyl radicals with an EC50 of 43.71 μg/ml. Antimicrobial screening, minimum inhibitory concentration, and minimum bactericidal concentration assays showed that the essential oil from M. alternifolia inhibited strongly the growth of different types of microorganisms, including Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Penicillium italicum Wehmer, and Penicillium digitatum Sacc. Thus, the essential oil of M. alternifolia possesses antioxidant and antimicrobial activity and could be suitable for use as a natural preservative ingredient in food, agriculture, and pharmaceutical industries.


Does ethanol activate G-protein coupled inwardly rectifying K+ channels?
G-protein coupled inwardly rectifying K+ (GIRK) channels have been reported to be targets of ethanol actions. We investigated if ethanol affects native GIRK channels in rat brain tissues at clinically relevant concentrations using brain slices containing the ventrolateral periaqueductal gray (PAG), an area related to pain regulation. Ethanol did not affect the membrane current elicited by hyperpolarization ramps at concentrations up to 150 mM. However, at 200-300 mM, which is above the lethal level, it activated a barium-sensitive GIRK current in 30-57% of neurons. In neurons unresponsive to ethanol, baclofen, the mu-opioid or nociceptin successfully activated GIRK channels. It is suggested that GIRK channels of the ventrolateral PAG are unlikely to be targets of the analgesic action of ethanol.


Yellow Perch (Perca flavescens) Mercury Unaffected by Wildland Fires in Northern Minnesota.
Wildland fire can alter mercury (Hg) cycling on land and in adjacent aquatic environments. In addition to enhancing local atmospheric Hg redeposition, fire can influence terrestrial movement of Hg and other elements into lakes via runoff from burned upland soil. However, the impact of fire on water quality and the accumulation of Hg in fish remain equivocal. We investigated the effects of fire-specifically, a low-severity prescribed fire and moderate-severity wildfire-on young-of-the-year yellow perch () and lake chemistry in a small remote watershed in the Boundary Waters Canoe Area Wilderness in northeastern Minnesota. We used a paired watershed approach: the fire-affected watershed was compared with an adjacent, unimpacted (reference) watershed. Prior to fire, upland organic horizons in the two study watersheds contained 1549 μg Hg m on average. Despite a 19% decrease in upland organic horizon Hg stocks due to the moderate severity wildfire fire, fish Hg accumulation and lake productivity were not affected by fire in subsequent years. Instead, climate and lake water levels were the strongest predictors of lake chemistry and fish responses in our study lakes over 9 yr. Our results suggest that low- to moderate-severity wildland fire does not alter lake productivity or Hg accumulation in young-of-the-year yellow perch in these small, shallow lakes in the northern deciduous and boreal forest region.


Comparative study between biofeedback retraining and botulinum neurotoxin in the treatment of anismus patients.
Anismus is a significant cause of chronic constipation. This study came to revive the results of BFB training and BTX-A injection in the treatment of anismus patients. Forty-eight patients with anismus (33 women; mean age 39.6 +/- 15.9) were included in this study. All patients fulfilled Rome II criteria for functional constipation. All patients underwent anorectal manometry, balloon expulsion test, defecography, and electromyography (EMG) activity of the EAS. All patients had non-relaxing puborectalis muscle. The patients were randomized into two groups. Group I patients received biofeedback therapy, two times per week for about 1 month. Group II patients were injected with BTX-A. Follow-up was conducted weekly in the first month then monthly for about 1 year. In the BFB training group, three patients quit before the end of sessions with no improvement; initial improvement was recorded in 12 patients (50%) while long-term success was recorded in six patients (25%). In the BTX-A group, clinical improvement was recorded in 17 patients (70.83%), but the improvement persisted only in eight patients (33.3%). There is a significant difference between BTX-A group and BFB group regarding the initial success, but this significant difference disappeared at the end of follow-up. Manometric relaxation was achieved significantly post-BFB and post-BTX-A injection with no significant difference between the two groups. Biofeedback training has a limited therapeutic effect on patients suffering from anismus. BTX-A injection seems to be successful for temporary treatment of anismus.


Argonaute2 regulates the pancreatic β-cell secretome.
Argonaute2 (Ago2) is an established component of the microRNA-induced silencing complex. Similar to miR-375 loss-of-function studies, inhibition of Ago2 in the pancreatic β-cell resulted in enhanced insulin release underlining the relationship between these two genes. Moreover, as the most abundant microRNA in pancreatic endocrine cells, miR-375 was also observed to be enriched in Ago2-associated complexes. Both Ago2 and miR-375 regulate the pancreatic β-cell secretome, and by using quantitative mass spectrometry, we identified the enhanced release of a set of proteins or secretion "signatures " in response to a glucose stimulus using the murine β-cell line MIN6. In addition, the loss of Ago2 resulted in the increased expression of miR-375 target genes, including gephyrin and ywhaz. These targets positively contribute to exocytosis indicating they may mediate the functional role of both miR-375 and Ago proteins in the pancreatic β-cell by influencing the secretory pathway. This study specifically addresses the role of Ago2 in the systemic release of proteins from β-cells and highlights the contribution of the microRNA pathway to the function of this cell type.


Brachytherapy for tongue cancer in the very elderly is an alternative to external beam radiation.
The result of curative treatment for very elderly patients with tongue carcinoma has not been reported to date. We retrospectively reviewed the results of brachytherapy in 125 the patients aged over 75 years. The results of brachytherapy in 125 patients, 75 years old or older, with Stage I or II squamous cell carcinoma of the oral tongue were reviewed. The 125 cases consisted of 31 Stage I and 94 Stage II cases; 67 patients were under 80 years old and 58 were over 80 years old. All patients were treated using low-dose-rate brachytherapy ((198)Au/(222)Rn: 59 cases; (192)Ir: 38 cases; (226)Ra/(137)Cs: 28 cases). None of the patients stopped treatment during the course of brachytherapy. The 3 year and 5 year control rates of the primary lesions were both 86%. Post-brachytherapy neck node metastasis was diagnosed in 43 cases and radical neck dissection was performed for 24 cases (21 of the 24 cases were under 80 years old). As a result, the 7 year disease-specific survival (DSS) rate for patients aged under 80 years old was 70% and 41% for those over 80 years old (p = 0.03). The brachytherapy for elderly patients with tongue cancer was safe, and the control of the primary lesion was almost the same as in younger patients. However, modalities available to treat neck node metastasis are limited. More conservative surgical approaches combined with post-operative irradiation may be advocated for neck node metastasis for elderly patients with tongue cancer.


Analgesia in hip fractures. Do fascia-iliac blocks make any difference?
Despite recent national advances in the care for the hip fracture patient, significant morbidity and mortality persists. Some of this morbidity is attributable to the analgesia provided in the hospital setting. The National Institute of Health and Care Excellence and the Association of Anaesthetists of Great Britain and Ireland recommend the use of simple oral analgesia including opioids, with fascia-iliac blocks (FIB) used as an adjunct. Literature review reveals a paucity of evidence on this. The aim of this project was to evaluate the proportion of patients receiving a fascia-iliac block prior to operative intervention. A secondary aim was to evaluate the efficacy of these blocks through analysis of pre and post-operative opioid usage, post-operative delirium, time to bowel opening, and naloxone use. Patients who received a fascia-iliac block received significantly less post-operative and total analgesia (p=0.04, p=0.03), had lower rates of delirium (p=0.03) and those patients which were discharged directly home had a shorter inpatient stay (p=0.03). No patients who received a fascia-iliac block (FIB) needed naloxone to reverse opioid toxicity, whilst two without fascia-iliac block did. The results of the project eventually led to the introduction of a hip fracture care pathway which incorporates a single shot fascia-iliac block for all patients who are eligible. Within a two year study period, compliance with fascia-iliac blocks improved from 54% to 90%. Our experience shows a great improvement in compliance with fascia-iliac blocks in the pre-operative period. This work has also underpinned the introduction of a new hip fracture care pathway ultimately to better patient care and outcomes.


Sex Matters in Aging. The Canagliflozin Story.
A promising and novel approach for identifying anti-aging therapeutics has been the repurposing of clinically approved and readily available drugs in mice. Canagliflozin, a clinically approved safe, and effective drug for type 2 diabetic patients, was recently shown to robustly retard age-related lesions in male mice but less so in female mice. While this type of sex disparity is often seen in the field of aging, it does represent a dilemma of not knowing the cause or how translationally relevant the sex differences would be in older humans treated with Canagliflozin. Thoughtful and mechanistic investigations are needed to understand why these differences are present and whether they can be eliminated by new drugs or drug combinations. Success in using repurposed drugs for aging intervention studies in humans will depend on preclinical research to uncover pathways that can be targeted for the benefit of both sexes.


Intracranial haemorrhage in patients on antithrombotics: clinical presentation and determinants of outcome in a prospective multicentric study in Italian emergency departments.
Intracranial haemorrhage (ICH) is the type of stroke associated with the highest death rate, and about 30% of ICH occurs in patients on antithrombotic treatment. This study relates clinical presentations and outcome of ICH patients on oral anticoagulant (OA) or antiplatelet (AP) therapy admitted to 33 Italian emergency departments (ED). Consecutive patients were enrolled after cranial computed tomography (CT). Primary outcome was the Modified Rankin Scale (MRS) score at 3 months of follow-up. Common descriptive statistics were computed after stratification for traumatic or spontaneous ICH and identification of the anatomical location of bleeding. Multivariate logistic regression was used to assess predictors of death. We recruited 434 patients on AP therapy and 232 on OA. There were 432 spontaneous and 234 traumatic ICH patients. The proportions of AP and OA patients undergoing neurosurgery were 21.8 and 19.4%, respectively, while < 30% underwent procoagulant medical treatment. At the 3-month follow-up, the case fatality rate was 42.0%, while disability or death (MRS 3-6) was 68.1%. The odds ratio for death in OA versus AP patients was 2.63 (95% CI 1.73-4.00) in the whole population and 2.80 (95% CI 1.77-4.41) in intraparenchymal event patients. Glasgow Coma Scale, age, spontaneous event and anticoagulant use were found to be predictors of death both in traumatic and spontaneous events. This study confirms the high prevalence of death or disability in OA and AP patients with ICH. As far as the determinants of mortality and disability are concerned, the results of this study might be useful in the clinical management and allocation of resources in the ED setting. The observed low use of procoagulant therapy highlights the need for ED educational programmes to heighten the awareness of available and effective haemostatic treatments.


Assessment of personality functioning in ICD-11 posttraumatic stress disorder and complex posttraumatic stress disorder.
The newly added diagnosis complex posttraumatic stress disorder (CPTSD) in the 11th edition of the International Classification of Diseases (ICD-11) includes a domain of disturbances in self-organization (DSO), in addition to PTSD. The DSO construct appears to have definitional overlap with the dimensional personality pathology severity measure, personality functioning. This study investigated the association between personality functioning and ICD-11 CPTSD, and the associations between DSO clusters and personality functioning domains. The sample comprised 83 outpatients with ICD-11 PTSD or CPTSD. Personality functioning was operationalized with the Level of Personality Functioning Scale (LPFS) and assessed with the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Alternative Model for Personality Disorders, Module I. Results showed an average level of moderate impairment in personality functioning (i.e., Identity, Self-Direction, Empathy, and Intimacy) for the whole sample. However, the levels of impairment in personality functioning were significantly more severe in patients with ICD-11 CPTSD, compared with patients with PTSD. Furthermore, the results revealed strong significant positive associations between the personality functioning domains and the DSO symptom clusters, except for the LPFS Identity domain and the DSO Affective Dysregulation cluster. Contrary to expectations, we found a significant positive association between the PTSD symptom cluster Avoidance and the LPFS domains Identity, Self-Direction, and Intimacy. Furthermore, higher levels of impairment in the Identity and Intimacy domain were associated with an increase in DSO symptom severity. New development in assessment of personality functioning may assist clinicians in differential diagnosis of PTSD and CPTSD. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Helix-coil kinetics of individual polyadenylic acid molecules in a protein channel.
Helix-coil transition kinetics of polyadenylic acid [poly(A)] inside a small protein channel is investigated for the first time, at the single molecule level. The confinement of a RNA molecule inside the channel slows its kinetics by nearly 3 orders of magnitude as compared to bulk measurements of free poly(A). These findings are related to the interaction energy of the RNA structure with the interior of the pore, explained by a simple two-state model. These results shed light on the way intermolecular interactions alter nucleic acid kinetics.


The valley of death: why Australia failed to develop clinically effective drugs in COVID-19.
There is a paucity of public discussion of costs spent on drug trials during coronavirus disease 2019 (COVID-19) and their value, and of large public outlay on research funding for vaccine and drug development that did not deliver medicines nor vaccines for Australians. This oversight left us at the behest of global supply chains, politics and commercial cost-plus pricing for vaccines. It is possible that these outcomes were the result of some major cognitive biases and the failure of a clinical pharmacologist's voice in the leadership teams. Biases included unawareness of the complexities of taking interesting chemicals in vitro to development into therapeutic use that can be tolerated, show efficacy and have appropriate disposition in humans; lack of a systems approach to therapeutic development; and an understanding of the relevance and translatability of pharmacology, physiology and clinical drug development. We believe that reflecting on and addressing these biases will help Australia reposition itself better with a therapeutics and clinical trial strategy for future pandemics, built into the strategy of a Centre for Disease Control.


Genome-wide survey of tandem repeats by nanopore sequencing shows that disease-associated repeats are more polymorphic in the general population.
Tandem repeats are highly mutable and contribute to the development of human disease by a variety of mechanisms. It is difficult to predict which tandem repeats may cause a disease. One hypothesis is that changeable tandem repeats are the source of genetic diseases, because disease-causing repeats are polymorphic in healthy individuals. However, it is not clear whether disease-causing repeats are more polymorphic than other repeats. We performed a genome-wide survey of the millions of human tandem repeats using publicly available long read genome sequencing data from 21 humans. We measured tandem repeat copy number changes using tandem-genotypes. Length variation of known disease-associated repeats was compared to other repeat loci. We found that known Mendelian disease-causing or disease-associated repeats, especially CAG and 5'UTR GGC repeats, are relatively long and polymorphic in the general population. We also show that repeat lengths of two disease-causing tandem repeats, in ATXN3 and GLS, are correlated with near-by GWAS SNP genotypes. We provide a catalog of polymorphic tandem repeats across a variety of repeat unit lengths and sequences, from long read sequencing data. This method especially if used in genome wide association study, may indicate possible new candidates of pathogenic or biologically important tandem repeats in human genomes.


Validation of a global quantitative analysis methodology of tryptophan metabolites in mice using LC-MS.
In this study, we validated a method for quantifying 20 tryptophan (Trp) catabolites by liquid chromatography coupled with high resolution mass spectrometry (LC-HRMS) in 4 different matrices (urine, serum, intestinal contents and liver). The detection limit for all metabolites ranged between 0.015 and 11.25 nmol/L and the dynamic range of the calibration curves were adjusted to allow quantification of metabolites at endogenous levels. Matrix effects were evaluated using isotope labeled internal standards. Reproducibility in the 4 matrices was characterized by CV = 6.2% with an accuracy of 6.6%. Our method has been applied to the determination and quantification of 20 metabolites concentrations in 5 different mouse compartments (plus cecal contents). Our results show that our approach allows for a global exploration of the Trp metabolism by quantifying a large number of Trp metabolites, at the individual level by multi-matrix approach.


Detection and Outcome of Endocervical Atypia in Cytology in Primary HPV Screening Programme.
Most endocervical adenocarcinomas (EAC) are associated with high-risk HPV (hrHPV) infection, with HPV genotypes 16, 18 and 45 accounting for >90% of the cases. Among endocervical glandular lesions, screening with hrHPV test has previously shown to predict the outcome better than cytology, although around one-fifth of the EAC remain negative both in hrHPV testing and cytology. The study consists of two consecutive HPV-primary screening rounds, conducted in 2012-2015 and 2017-2020. Of the 87 women aged 35 to 60 years of age diagnosed with Atypical endocervical cells, NOS or Atypical endocervical cells, favor neoplastic cytology during the first screening round, 63 (72.4%) were hrHPV positive and 24 (27.6%) were hrHPV negative. Among hrHPV positive patients, three EAC, two adenocarcinomas in situ (AIS), one AIS + high-grade intraepithelial lesion (HSIL) and 13 HSIL were found. Of the histologically verified lesions, 68.4% (13/19) were purely of squamous origin. All the EAC and AIS were HPV16 or HPV 18 positive. No high-grade histological lesions were found among the hrHPV negative patients with cytological glandular atypia. A later database search revealed one HPV-negative, gastric-type mucinous EAC that was missed by the HPV primary screening.


Pagetoid reticulosis and solitary mycosis fungoides. Distinct clinicopathological entities.
The two cases reported in this paper allow the differentiation of pagetoid reticulosis from solitary lesions of mycosis on the basis of clinical, histological ultrastructural, immunohistochemical and enzyme histochemical studies. The first patient presented with a slowly growing asymptomatic scaly plaque of 30 years duration. Histology of the lesion was typical of pagetoid reticulosis. Immunohistochemical studies showed that the abnormal cells present in the cutaneous infiltrate were not T lymphocytes and ultrastructural studies suggested these were of histocytic origin. The second patient presented with a poikilodermatous lesion present for 14 years with histology of plaque stage mycosis fungoides. Enzyme and immunohistochemistry showed the predominant T cell nature of the cutaneous infiltrate and electron microscopy showed numerous mycosis fungoides cells. In contrast to generalized forms of mycosis fungoides, no peripheral blood monocyte chemotactic defect was found in either case. Both lesions responded to radiotherapy.


Re-Envisioning an Early Years System of Care towards Equity in Canada: A Critical, Rapid Review.
Background: Many children in high-income countries, including Canada, experience unjust and preventable health inequities as a result of social and structural forces that are beyond their families' immediate environment and control. In this context, early years programs, as a key population health initiative, have the potential to play a critical role in fostering family and child wellbeing. Methods: Informed by intersectionality, this rapid literature review captured a broad range of international, transdisciplinary literature in order to identify promising approaches for orienting early years systems of care towards equity in Canada. Results: Findings point to the need for a comprehensive, integrated and socially responsive early years system that has top-down political vision, leadership and accountability and bottom-up community-driven tailoring with an explicit focus on health promotion and maternal, family and community wellness using relational approaches. Conclusions: Advancing child health equity in wealthy countries requires structural government-level changes that support cross-ministerial and intersectoral alliances. Employing intersectionality in this rapid review promotes contextualized and nuanced understandings of what is needed in order to advance a responsive, comprehensive and quality early years system of equity-oriented care. Further research is needed to prevent child health inequities that are disproportionally experienced by Indigenous and racialized children in wealthy countries such as Canada. olicy and research recommendations that have relevance for high-income countries in diverse global contexts are discussed.


The effect of support surface and footwear condition on postural sway and lower limb muscle action of the older women.
Diminished somatosensory function is a critical age-related change which is related to postural instability in the older population. Footwear is a cost-effective way to modulate the postural stability by altering sensorimotor inputs via mechanoreceptors on the plantar surface of the feet. Compared to insoles with indentions in the entire surface, we innovatively developed a textured insole with site-specific nodulous protrudous. This study thus aimed to investigate the immediate effect of the nodulous insole and supporting surface condition on static postural stability and lower limb muscle activation for healthy older women. This is a single-session study with repeated measurements. Twenty-three healthy older women stood on the firm (i.e., concrete floor) and foam surfaces with their eyes open in the three footwear conditions, namely barefoot, plain shoes and shoes with an innovative textured insole, for 30 seconds. Static postural sway and muscle activation of biceps femoris (BF), vastus lateralis (VL), tibialis anterior (TA), and lateral gastrocnemius (LG) of the dominant leg were measured during each testing condition. Compared to a firm surface, standing on the foam could significantly increase the body sway and lower limb muscle activation (p<0.05). When standing on the foam, compared to barefoot, wearing footwear significantly decreased the VL and TA muscle activation and minimize the postural sway in medial-lateral and anterior-posterior direction, while the influence is larger for the shoes with nodulous insloe compared to the plain shoes. No significant differences between the footwear conditions for static stability and muscle activation were observed on firm surface condition. For older women, footwear could improve the postural stability in the unstable surface, particularly the footwear with nodulous insole, with the underlying mechanism as enhancing the mechanoreceptors on the plantar surface of the feet.


Oxidized Low-Density Lipoprotein and the Incidence of Proliferative Diabetic Retinopathy and Clinically Significant Macular Edema Determined From Fundus Photographs.
Studies have shown oxidized low-density lipoprotein to be associated with the incidence of proliferative retinopathy and other complications of type 1 diabetes mellitus. Because low-risk interventions are available to modify oxidized low-density lipoprotein, it is important to examine the relationships between this factor and the incidence of proliferative retinopathy and of macular edema, 2 important causes of visual impairment in people with type 1 diabetes. To determine the association of oxidized low-density lipoprotein with the worsening of diabetic retinopathy and the incidence of proliferative retinopathy and of macular edema. Of 996 participants with type 1 diabetes in the Wisconsin Epidemiologic Study of Diabetic Retinopathy, 730 were examined up to 4 times (1990-1992, 1994-1996, 2005-2007, and 2012-2014) over 24 years and had assays of oxidized low-density lipoprotein and fundus photographs gradable for diabetic retinopathy and macular edema. Analyses started July 2014 and ended February 2015. Worsening of diabetic retinopathy, incidence of proliferative diabetic retinopathy, and incidence of macular edema as assessed via grading of color stereo film fundus photographs. The levels of oxidized low-density lipoprotein collected from serum samples at the time of each examination were measured in 2013 and 2014 from frozen serum. The cohort at baseline had a mean (SD) level of oxidized low-density lipoprotein of 30.0 (8.5) U/L. While adjusting for duration of diabetes, glycated hemoglobin A1c level, and other factors, we found that neither the level of oxidized low-density lipoprotein at the beginning of a period nor the change in it over a certain period was associated with the incidence of proliferative diabetic retinopathy (hazard ratio [HR], 1.11 [95% CI, 0.91-1.35], P = .30; odds ratio [OR], 1.77 [95% CI, 0.99-3.17], P = .06), the incidence of macular edema (HR, 1.04 [95% CI, 0.83-1.29], P = .74; OR, 1.08 [95% CI, 0.44-2.61], P = .87), or the worsening of diabetic retinopathy (HR, 0.94 [95% CI, 0.83-1.07], P = .34; OR, 1.32 [95% CI, 0.83-2.09], P = .24). Our findings do not provide evidence for a relationship between increasing levels of serum oxidized low-density lipoprotein and the incidence of macular edema or the worsening of diabetic retinopathy in persons with type 1 diabetes. The potential increase in the HR for incident proliferative retinopathy, with an increase in oxidized low-density lipoprotein level over the preceding period, warrants further investigation of this relationship.


Tracking the use and impact of a community social report: where does the information go?
The purpose of this paper is to report on a study evaluating the extent to which a social report (entitled "Hamilton-Wentworth Profile on Children and Youth") was read and used by recipients. Subjects were divided into two groups: an Active Group which had worked on producing the Profile and/or requested copies of it once it had been released, and a Passive Group which had received copies of the Profile through a general mailing list used for other research reports. Approximately one year later, 90% of the Active Group recalled the Profile compared to 21% of the Passive Group. Similarly, 83% of Active Group respondents had read the Profile compared to 8% of Passive Group subjects. 80% of Active Group respondents and 5% of Passive Group respondents used the Profile. The results suggest that if social reports are read by local community agencies and individuals, they will be used to help improve conditions for children and youth. Social reports at the local level are more likely to be read if potential users are engaged in the process of report production and if the reports are disseminated to the appropriate target audience.


The β4 subunit of Cav1.2 channels is required for an optimal interferon response in cardiac muscle cells.
The auxiliary β4 subunit of the cardiac Cav1.2 channel plays a poorly understood role in gene transcription. Here, we characterized the regulatory effects of the β4 subunit in H9c2 rat cardiac cells on the abundances of Ifnb mRNA [which encodes interferon-β (IFN-β)] and of the IFN-β-related genes Ddx58, Ifitm3, Irf7, Stat2, Ifih1, and Mx1, as well as on the abundances of the antiviral proteins DDX58, IRF7, STAT2, and IFITM3. Knocking down the β4 subunit in H9c2 cells reduced the expression of IFN-β-stimulated genes. In response to inhibition of the kinase JAK1, the abundances of β4 subunit mRNA and protein were decreased. β4 subunit abundance was increased, and it translocated to the nucleus, in cells treated with IFN-β, infected with dengue virus (DENV), or transfected with poly(I:C), a synthetic analog of double-stranded RNA. Cells that surrounded the virus-infected cells showed translocation of β4 subunit proteins to nuclei in response to spreading infection. We showed that the β4 subunit interacted with the transcriptional regulator IRF7 and that the activity of an Irf7 promoter-driven reporter was increased in cells overexpressing the β4 subunit. Last, overexpressing β4 in undifferentiated and differentiated H9c2 cells reduced DENV infection and decreased the abundance of the viral proteins NS1, NS3, and E-protein. DENV infection and poly(I:C) also increased the concentration of intracellular Ca2+ in these cells. These findings suggest that the β4 subunit plays a role in promoting the expression of IFN-related genes, thereby reducing viral infection.


Exosomes and pancreatic diseases: status, challenges, and hopes.
Pancreatic disease, including pathologies such as acute pancreatitis (AP), chronic pancreatitis (CP), and pancreatic cancer (PC), is a complicated and dangerous clinical condition involving the disruption of exocrine or endocrine function. PC has one of the highest mortality rates among cancers due to insufficient diagnosis in early stages. Furthermore, efficient treatment options for the disease etiologies of AP and CP are lacking. Thus, the identification of new therapeutic targets and reliable biomarkers is required. As essential couriers in intercellular communication, exosomes have recently been confirmed to play an important role in pancreatic disease, but the specific underlying mechanisms are unknown. Herein, we summarize the current knowledge of exosomes in pancreatic disease with respect to diagnosis, molecular mechanisms, and treatment, proposing new ideas for the study of pancreatic disease.