Microemboli detection and classification by innovative ultrasound technology during simulated neonatal cardiopulmonary bypass at different flow rates, perfusion modes, and perfusate temperatures

The objective of this study was to detect and classify the number and size of gaseous microemboli in a simulated pediatric model of cardiopulmonary bypass. Tests were conducted at five different flow rates (400-1,200 ml/min in 200 ml/min increments), pulsatile versus nonpulsatile perfusion modes, and under normothermic, hypothermic, and deep hypothermic (35 degrees C, 25 degrees C, and 15 degrees C) conditions, yielding 180 total experiments. The circuit was primed with lactated Ringer's solution and filled with heparinized bovine blood. At the beginning of each experiment, 5 ml of air were injected into the venous line via the luer port of the oxygenator. Microemboli were quantified and classified by size for 5 minute segments at three transducer sites: postpump, postoxygenator, and postarterial filter. The purge line of the arterial filter was closed during all experiments. In all but one experiment, 90% of emboli at the postpump site were found to be smaller than 40 microm. At the postarterial filter site, nearly 99% of the emboli were smaller than 40 microm. Additionally, increasing microemboli counts were observed when the flow rate was increased and when the temperature was decreased. Lower temperatures, higher flow rates, and pulsatile perfusion were all associated with higher emboli counts. The majority of gaseous microemboli found in the simulated circuit was significantly below 40 microm; the smallest level detectable by traditional Doppler devices.     

Preventive and therapeutic potential of p38 alpha-selective mitogen-activated protein kinase inhibitor in nonobese diabetic mice with type 1 diabetes

Mitogen-activated protein kinases (MAPKs) and heat shock proteins (HSPs) are ubiquitous proteins that function within T cells in both normal and stress-related pathophysiological states, including type 1 diabetes. The nonobese diabetic (NOD) mouse spontaneously develops T cell-mediated autoimmune pancreatic beta cell destruction that is similar to type 1 diabetes in humans. Because p38 MAPKs have been shown to modulate T cell function, we studied the effects of a p38alpha MAPK-selective inhibitor, indole-5-carboxamide (SD-169), on the development and progression of type 1 diabetes in the NOD mouse. In preventive treatment studies, SD-169 significantly reduced p38 and HSP60 expression in T cells of the pancreatic beta islets. Following treatment, the incidence of diabetes as determined by blood glucose levels was significantly lower, and immuno-histochemistry of pancreatic beta islet tissue demonstrated significant reduction in CD5+ T cell infiltration in the SD-169 treatment group as compared with untreated NOD mice. In therapeutic studies using mildly and moderately hyperglycemic NOD mice, SD-169 treatment lowered blood glucose and improved glucose homeostasis. Furthermore, following cessation of SD-169 treatment, NOD mice showed significant arrest of diabetes. In conclusion, we report that this p38alpha-selective inhibitor prevents the development and progression of diabetes in NOD mice by inhibiting T cell infiltration and activation, thereby preserving beta cell mass via inhibition of the p38 MAPK signaling pathway. These results have bearing on current prophylactic and therapeutic protocols using p38alpha-selective inhibitors in the prediabetic period for children at high risk of type 1 diabetes, in the honeymoon period, and for adults with latent autoimmune diabetes.     

Investigation of an efficient source design for Cobalt-60-based tomotherapy using EGSnrc Monte Carlo simulations

Recent investigations demonstrate a strong potential for Cobalt-60 (Co-60)-based tomotherapy. Reported work suggests that Co-60-based tomotherapy offers a clinically and commercially viable alternative to megavoltage x-ray-based tomotherapy. Tomotherapy applications use a combination of intensity-modulated fan beams to deliver highly conformal radiotherapy. However, conventional Co-60 units are designed to give large uniform rectangular fields using an isotropic radioactive source in a cylindrical geometry. Such cylindrical source geometry likely provides a sub-optimal use of the radioactivity within the source volume for tomotherapy applications due to a significant loss of radiated energy outside the fan beam collimation system. To investigate a more efficient source geometry suitable for Co-60 tomotherapy applications, a computer code was written to model an isotropic source in a 6-faced polyhedron geometry such as cube, parallelepiped, prism and truncated pyramid. This code was integrated with the existing EGSnrc/BEAMnrc Monte Carlo (MC) code. The integrated source code was thoroughly tested, validated and used to investigate the energy spectra, radiation output and self-shielding properties of various rectangular-shaped (RS) Co-60 sources. Fan beam dose profiles were calculated for various cylindrical and RS Co-60 sources for a range of source-to-axis distances (SAD), multi-leaf collimator-to-isocentre distances (CID) and modified collimator systems. Fringe and penumbra distances were analysed for the simulated dose profiles. Our results demonstrate that clinically acceptable fringe and penumbra distances can be achieved by a careful selection of SAD, CID, source shape and dimensions and modified collimator system. Significant overall gain in radiation output of the 20 x 1 cm(2) fan beams can be achieved by an optimal selection of the source geometry for a given active volume of Co-60. The overall gain includes the effects of change in packing density (accounting for self-absorption) and change in source shape.     

Slow‐wave sleep and motor progression in Parkinson disease

Growing evidence from Alzheimer disease supports a potentially beneficial role of slow‐wave sleep in neurodegeneration. However, the importance of slow‐wave sleep in Parkinson disease is unknown. In 129 patients with Parkinson disease, we retrospectively tested whether sleep slow waves, objectively quantified with polysomnography, relate to longitudinal changes in Unified Parkinson's Disease Rating Scale motor scores. We found that higher accumulated power of sleep slow waves was associated with slower motor progression, particularly of axial motor symptoms, over a mean time of 4.6 ± 2.3 years. This preliminary finding suggests that deeper sleep relates to slower motor progression in Parkinson disease. Ann Neurol 2019;85:765–770     

Early-life Chronic Stressors,Rumination, and the Onset of Vulvodynia

IntroductionVulvodynia is a debilitating, chronic vulvar pain condition. Community-based case-control studies have consistently shown associations between early-life chronic stressors and vulvodynia onset.AimWe examined rumination as a specific stress response involved in the psychobiological mechanism of vulvodynia.MethodsA psychosocial survey with questions specific to early-life traumatic events and rumination were administered to 185 matched case-control pairs of women with and without vulvodynia. Conditional logistic regression was used to examine associations between rumination constructs (ie, total rumination, emotion-focused, instrumental, and searching for meaning) and vulvodynia onset. Conditional logistic regression was also used to determine whether these associations depended on early-life stressors (ie, severity of childhood abuse and of self-reported antecedent traumatic events). Age at interview, antecedent pain disorders, any childhood abuse, and antecedent psychiatric morbidity were included as covariates.Main Outcome MeasuresWe estimated the odds of rumination in relation to the onset of vulvodynia within a community-based and clinically confirmed sample of women with and without vulvodynia.ResultsVulvodynia was associated with the highest tertile of emotion-focused (odds ratio [OR] = 2.1; 95% CI = 1.2, 3.2) and instrumental (OR = 2.1; 95% CI = 1.1, 4.0) rumination. These associations were attenuated after additional adjustment for antecedent psychiatric morbidity. Among women who reported rumination about early-life stressors before vulvar pain in cases or matched reference age in control subjects, those with vulvodynia were >2 times more likely to report the highest tertile of total rumination (OR = 2.3; 95% CI = 1.1, 5.0) compared with those without vulvodynia.Clinical ImplicationsHealthcare providers may be able to identify subsets of women who could benefit from preventive measures before the development of vulvodynia.Strength & LimitationsThis is the first study to use a community-based and clinically confirmed sample of women with and without vulvodynia to examine the associations between rumination about early-life trauma and the onset of vulvodynia. However, as with all retrospective studies, the reporting of information (eg, traumatic events) was subject to recall bias and misclassification.ConclusionOur findings indicate that a prolonged cognitive stress response (ie, rumination) may be 1 important mechanism by which early-life chronic stressors contribute to the onset vulvodynia. Prospective studies are recommended to examine whether and how cognitive, affective, and physiological components of prolonged stress responses interact to influence the development of vulvodynia. Understanding both the psychobiological and behavioral mechanisms may help in addressing and treating individuals to potentially reverse the development of vulvodynia.Khandker M, Brady SS, Rydell SA, et al. Early-life Chronic Stressors, Rumination, and the Onset of Vulvodynia. J Sex Med 2019;16:880–890.     

Eating Behavior as a Prognostic Factor for Weight Loss after Gastric Bypass

BACKGROUND: Binge-eating disorder (BED) may be associated with unsatisfactory weight loss in obese patients submitted to bariatric procedures. This study aims to investigate whether the presence of binge eating before Roux-en-Y gastric bypass (RYGBP) influences weight outcomes. METHODS: In a prospective design, 216 obese patients (37 males, 178 females, BMI=45.9 +/- 6.0 kg/m2) were assessed for the lifetime prevalence of BED and classified at structured interview into 3 subgroups: no binge eating (NBE=43), sub-threshold binge eating (SBE=129), and binge-eating disorder (BED=44). All patients were encouraged to take part in a multidisciplinary program following surgery, and weight loss at follow-up was used as the outcome variable. RESULTS: At 1-year follow-up, NBE patients (n=41) showed percent excess BMI loss (%EBL) significantly higher than SBE patients (n=112) (P=0.027), although this effect was not significantly different between NBE and BED patients (n=44). At 2-year follow-up, NBE patients (n=33) showed %EBL higher than SBE (n=64) (P=-0.003) and BED patients (n=34) (P<0.001). Nevertheless, we found no significant weight loss differences between SBE (subclinical) and BED (full criteria) patients at any period of follow-up. Preliminary results at 3-year follow-up suggest that such an effect may be enduring. CONCLUSION: The presence of a history of binge eating prior to treatment is associated with poorer weight loss in obese patients submitted to RYGBP. Because BED is highly prevalent in obese patients seeking bariatric surgery, its early recognition and treatment may be of important clinical value.     

Improving the osteointegration and bone–implant interface by incorporation of bioactive particles in sol–gel coatings of stainless steel implants

In this study, we report a hybrid organic–inorganic TEOS–MTES (tetraethylorthosilicate–methyltriethoxysilane) sol–gel-made coating as a potential solution to improve the in vivo performance of AISI 316L stainless steel, which is used as permanent bone implant material. These coatings act as barriers for ion migration, promoting the bioactivity of the implant surface. The addition of SiO₂ colloidal particles to the TEOS–MTES sol (10 or 30 mol.%) leads to thicker films and also acts as a film reinforcement. Also, the addition of bioactive glass–ceramic particles is considered responsible for enhancing osseointegration. In vitro assays for bioactivity in simulated body fluid showed the presence of crystalline hydroxyapatite (HA) crystals on the surface of the double coating with 10 mol.% SiO₂ samples on stainless steel after 30 days of immersion. The HA crystal lattice parameters are slightly different from stoichiometric HA. In vivo implantation experiments were carried out in a rat model to observe the osteointegration of the coated implants. The coatings promote the development of newly formed bone in the periphery of the implant, in both the remodellation zone and the marrow zone. The quality of the newly formed bone was assessed for mechanical and structural integrity by nanoindentation and small-angle X-ray scattering experiments. The different amount of colloidal silica present in the inner layer of the coating slightly affects the material quality of the newly formed bone but the nanoindentation results reveal that the lower amount of silica in the coating leads to mechanical properties similar to cortical bone.     

Older women with diabetes have a higher risk of falls: a prospective study

OBJECTIVE: To determine whether older women with diabetes have an increased risk of falls and whether known risk factors for falls account for any increased risk. RESEARCH DESIGN AND METHODS: This prospective cohort study included 9,249 women > or =67 years of age enrolled in the Study of Osteoporotic Fractures. Diabetes was determined by questionnaire at baseline. Physical performance was measured at the second examination. Subsequently, falls were ascertained every 4 months by postcard. RESULTS: A total of 629 (6.8%) women had diabetes, including 99 who used insulin. During an average of 7.2 years, 1,640 women (18%) fell more than once a year. Diabetes, stratified by insulin use, was associated with an increased risk of falling more than once a year (age-adjusted odds ratio [OR] 1.68 [95% CI 1.37-2.07] for non-insulin-treated diabetes; age-adjusted OR 2.78 [1.82-4.24] for insulin-treated diabetes). In the first 2 years of follow-up, women with diabetes were not more likely to fall than women without diabetes (44 vs. 42%; P = 0.26), but they had more falls (3.1 vs. 2.4; P < 0.01). Women with diabetes were more likely to have other risk factors for falls, which appeared to account for the increased risk of falls associated with non-insulin-treated diabetes (adjusted OR 1.18 [0.87-1.60]) but not insulin-treated diabetes (adjusted OR 2.76 [1.52-5.01]). CONCLUSIONS: Older women with diabetes have an increased risk of falling, partly because of the increased rates of known fall risk factors, and may benefit from interventions to prevent falls. Further research is needed to determine whether diabetes treatment reduces fall risk.