Magnitude of A1C improvement in relation to baseline A1C and amount of weight loss in response to intensive lifestyle intervention in real-world diabetes practice: 13 years of observation.

BACKGROUND: Effect of intensive lifestyle intervention (ILI) on A1C in participants with diabetes is underestimated. A1C improvement is presumed to be dependent on the amount of weight loss. Here, we evaluate the magnitude of A1C change in relation to baseline A1C and the amount of weight loss in participants with diabetes who underwent ILI over 13 years in real-world clinical practice. METHODS: A total of 590 participants with diabetes were enrolled in the Weight Achievement and Intensive Treatment (Why WAIT) program, a 12-week multidisciplinary ILI program designed for real-world clinical practice between September 2005 and May 2018. We stratified participants based on baseline A1C into three groups: group A: A1C ≥ 9%, group B: A1C 8 to <9%, and group C: A1C ≥6.5% to <8%. RESULTS: After 12-weeks of intervention, body weight decreased in all groups, and pairwise comparisons of A1C changes showed that: group A had 1.3% greater A1C reduction than group B (p = 0.0001) and 2% greater than group C (p = 0.0001), while group B had 0.7% greater A1C reduction than group C (p = 0.0001). CONCLUSION: We conclude that ILI may decrease A1C by up to 2.5% in participants with diabetes. At similar magnitude of weight loss, A1C reduction was more prominent in participants with higher baseline A1C. This may be valuable for clinicians to set a realistic expectation of A1C change in response to ILI.

Multidisciplinary intensive lifestyle intervention improves markers of nonalcoholic fatty liver disease (NAFLD) in patients with type 1 diabetes and obesity: a retrospective matched-cohort study.

BACKGROUND: The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing among patients with type 1 diabetes (T1D) paralleling the increasing prevalence of obesity among this population. However, little is known about the impact of intensive lifestyle intervention (ILI) on NAFLD in patients with T1D. METHODS: Using Hepatic Steatosis Index (HSI), a noninvasive surrogate predictor of NAFLD, we retrospectively evaluated 88 adult patients with T1D and obesity after one year of participating in a 12-week ILI program in real-world clinical practice. Using the NAFLD guidelines of the American Association for the Study of Liver Diseases (AASLD), we excluded 11 participants. We matched the remaining ILI cohort (age 43 ± 12 years, females 65%, diabetes duration 22 ± 9 years, A1C 8.2 ± 0.9%, body weight 101 ± 17 kg, BMI 35.3 ± 4.9 kg/m2) in 1:1 ratio with a similar cohort of patients with T1D and obesity who received standard diabetes care (SC) at the same practice and during the same period. Matching criteria included: sex, age, BMI, A1C and duration of T1D. HSI [8 + ALT/AST + BMI (+ 2 if female, + 2 if T2D)] was calculated at baseline and after 12 months of intervention. RESULTS: At baseline, HSI was similar between the two cohorts (46.2 ± 6.1 in the ILI cohort and 44.9 ± 5.7 in the SC cohort). After 12 months, the ILI group lost an average of 5.6 ± 2.7 kg (5.8%, p < 0.05) while the SC group maintained their baseline body weight (p < 0.001 between groups). HSI decreased significantly from baseline in the ILI group (-2.7 ± 1.1, p = 0.01), but did not change in the SC group (0.6 ± 0.9, p = 0.53, p < 0.001 between groups). Percentage of patients with high likelihood of NAFLD diagnosis decreased from 100% at baseline to 88.3% in the ILI group, and was 10.4% less compared to SC (p < 0.01). Total daily insulin dose decreased in the ILI cohort compared to the SC cohort (-6.1 ± 4.2 versus 1.34 ± 4.3 units/day, p < 0.01). CONCLUSIONS: Twelve weeks of ILI improved HSI and decreased total daily insulin requirements in patients with T1D and obesity at one year. Short-term ILI should be implemented in the management of NAFLD for obese patients with type 1 diabetes.

Altered bed nucleus of the stria terminalis and amygdala responses to threat in combat veterans with posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) significantly impacts many veterans. Although PTSD has been linked to alterations in the fear brain network, the disorder likely involves alterations in both the fear and anxiety networks. Fear involves responses to imminent, predictable threat and is driven by the amygdala, whereas anxiety involves responses to potential, unpredictable threat and engages the bed nucleus of the stria terminalis (BNST). The BNST has been implicated in PTSD, but the role of the BNST in combat veterans with PTSD has yet to be examined. Identifying alterations in BNST responses to unpredictable threat could provide important new targets for treatment. The current study examined whether veterans with PTSD have altered BNST or amygdala responses (function and connectivity) to unpredictable and predictable threat. The fMRI task involved viewing predictable threat cues followed by threat images, predictable neutral cues followed by neutral images, and unpredictable threat cues followed by either a threat or neutral image. Participants included 32 combat-exposed veterans with PTSD and 13 combat-exposed controls without PTSD. Across all conditions, veterans with PTSD had heightened BNST activation and displayed stronger BNST and amygdala connectivity with multiple fear and anxiety regions (hypothalamus, hippocampus, insula, ventromedial prefrontal cortex) relative to controls. In contrast, combat controls showed a pattern of stronger connectivity during neutral conditions (e.g., BNST-vmPFC), which may suggest a neural signature of resilience to developing PTSD, ηp 2 = .087-.527, ps < .001. These findings have implications for understanding fear and anxiety networks that may contribute to the development and maintenance of PTSD.

Social determinants of health and the double burden of disease in Nepal: a secondary analysis.

BACKGROUND: As the global burden of disease evolves, lower-resource countries like Nepal face a double burden of non-communicable and infectious disease. Rapid adaptation is required for Nepal's health system to provide life-long, person-centred care while simultaneously improving quality of infectious disease services. Social determinants of health be key in addressing health disparities and could direct policy decisions to promote health and manage the disease burden. Thus, we explore the association of social determinants with the double burden of disease in Nepal. METHODS: This is a retrospective, ecological, cross-sectional analysis of infectious and non-communicable disease outcome data (2017 to 2019) and data on social determinants of health (2011 to 2013) for 753 municipalities in Nepal. Multinomial logistic regression was conducted to evaluate the associations between social determinants and disease burden. RESULTS: The 'high-burden' combined double burden (non-communicable and infectious disease) outcome was associated with more accessible municipalities, (adjOR3.94[95%CI2.94-5.28]), municipalities with higher proportions of vaccine coverage (adjOR12.49[95%CI3.05-51.09]) and malnutrition (adjOR9.19E103[95%CI19.68E42-8.72E164]), lower average number of people per household (adjOR0.32[95%CI0.22-0.47]) and lower indigenous population (adjOR0.20[95%CI0.06-0.65]) compared to the 'low-burden' category on multivariable analysis. 'High-burden' of non-communicable disease was associated with more accessible municipalities (adjOR1.93[95%CI1.45-2.57]), higher female proportion within the municipality (adjOR1.69E8[95%CI3227.74-8.82E12]), nutritional deficiency (adjOR1.39E17[95%CI11799.83-1.64E30]) and malnutrition (adjOR2.17E131[95%CI4.41E79-1.07E183]) and lower proportions of population under five years (adjOR1.05E-10[95%CI9.95E-18-0.001]), indigenous population (adjOR0.32[95%CI0.11-0.91]), average people per household (adjOR0.44[95%CI0.26-0.73]) and households with no piped water (adjOR0.21[95%CI0.09-0.49]), compared to the 'low-burden' category on adjusted analysis. 'High burden' of infectious disease was also associated with more accessible municipalities (adjOR4.29[95%CI3.05-6.05]), higher proportions of population under five years (adjOR3.78E9[95%CI9418.25-1.51E15]), vaccine coverage (adjOR25.42[95%CI7.85-82.29]) and malnutrition (adjOR4.29E41[95%CI12408.29-1.48E79]) and lower proportions of households using firewood as fuel (adjOR0.39[95%CI0.20-0.79]) ('moderate-burden' category only) compared to 'low-burden'. CONCLUSIONS: While this study produced imprecise estimates and cannot be interpreted for individual risk, more accessible municipalities were consistently associated with higher disease burden than remote areas. Female sex, lower average number per household, non-indigenous population and poor nutrition were also associated with higher burden of disease and offer targets to direct interventions to reduce the burden of infectious and non-communicable disease and manage the double burden of disease in Nepal.

The Development of Videoconference-Based Support for People Living With Rare Dementias and Their Carers: Protocol for a 3-Phase Support Group Evaluation.

BACKGROUND: People living with rarer dementias face considerable difficulty accessing tailored information, advice, and peer and professional support. Web-based meeting platforms offer a critical opportunity to connect with others through shared lived experiences, even if they are geographically dispersed, particularly during the COVID-19 pandemic. OBJECTIVE: We aim to develop facilitated videoconferencing support groups (VSGs) tailored to people living with or caring for someone with familial or sporadic frontotemporal dementia or young-onset Alzheimer disease, primary progressive aphasia, posterior cortical atrophy, or Lewy body dementia. This paper describes the development, coproduction, field testing, and evaluation plan for these groups. METHODS: We describe a 3-phase approach to development. First, information and knowledge were gathered as part of a coproduction process with members of the Rare Dementia Support service. This information, together with literature searches and consultation with experts by experience, clinicians, and academics, shaped the design of the VSGs and session themes. Second, field testing involved 154 Rare Dementia Support members (people living with dementia and carers) participating in 2 rounds of facilitated sessions across 7 themes (health and social care professionals, advance care planning, independence and identity, grief and loss, empowering your identity, couples, and hope and dementia). Third, a detailed evaluation plan for future rounds of VSGs was developed. RESULTS: The development of the small groups program yielded content and structure for 9 themed VSGs (the 7 piloted themes plus a later stages program and creativity club for implementation in rounds 3 and beyond) to be delivered over 4 to 8 sessions. The evaluation plan incorporated a range of quantitative (attendance, demographics, and geography; pre-post well-being ratings and surveys; psycholinguistic analysis of conversation; facial emotion recognition; facilitator ratings; and economic analysis of program delivery) and qualitative (content and thematic analysis) approaches. Pilot data from round 2 groups on the pre-post 3-word surveys indicated an increase in the emotional valence of words selected after the sessions. CONCLUSIONS: The involvement of people with lived experience of a rare dementia was critical to the design, development, and delivery of the small virtual support group program, and evaluation of this program will yield convergent data about the impact of tailored support delivered to geographically dispersed communities. This is the first study to design and plan an evaluation of VSGs specifically for people affected by rare dementias, including both people living with a rare dementia and their carers, and the outcome of the evaluation will be hugely beneficial in shaping specific and targeted support, which is often lacking in this population. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/35376.

On-farm evaluation of a predictive model for Australian beef and sheep producers' vulnerability to an outbreak of foot and mouth disease.

To explore Australian sheep and beef producer vulnerability to an emergency animal disease outbreak, Bayesian Network models have been developed, with the ultimate goal of creating risk management tool for outbreak preparedness. These models were developed using multiple stakeholder elicitation including modelling experts, epidemiologists and on-farm stakeholders, including on-farm/survey data. An evaluation of the model's predictive capacity was conducted, using independent, blinded on-farm vulnerability assessments. Nine properties were visited, four each with sheep and beef enterprises, and one mixed enterprise. There were some discrepancies between the model predictions and on-farm assessment in the beef enterprises, with greater disparity with the sheep properties. Discrepancies between the model predictions and on-farm assessments have created opportunities for examination of the data collection process for the model development, the model itself and the on-farm assessment process. Bayesian Network approaches that allow for the inclusion of both continuous and discrete variables may improve the usefulness of these models, avoiding the loss of nuanced data by the need for discretisation of continuous variables, as will the inclusion of input from on-farm stakeholders in model development. Future work includes more data collection to improve the sensitivity of the model predictions, and a deeper, systemic exploration of the factors that may impact Australian producers' vulnerability to an emergency animal disease outbreak.

In-person and virtual multidisciplinary intensive lifestyle interventions are equally effective in patients with type 2 diabetes and obesity.

Background: Intensive lifestyle intervention (ILI) is essential for diabetes management. The Weight Achievement and Intensive Treatment (Why WAIT) program is a 12-week multidisciplinary weight management program that has been implemented in real-world clinical practice since 2005 and has shown long-term maintenance of weight reduction for 5 and 10 years. During the COVID-19 pandemic, the program went virtual using telemedicine and mobile health applications. Aims: This retrospective pilot study aims to evaluate the effectiveness of a virtual model of an already established and successful in-person program for diabetes and weight management since 2005. Methods: We evaluated 38 patients with diabetes and obesity enrolled in the Why WAIT program between February 2019 and December 2020. Sixteen participants were enrolled in virtual program (VP) and were compared with 22 participants who completed the latest two physical programs (PPs) before COVID-19. We evaluated changes in body weight, A1C, blood pressure (BP), and lipid profile after 12 weeks of ILI. Results: Body weight decreased by -7.4 ± 3.6 kg from baseline in VP compared with -6.8 ± 3.5 kg in PP (p = 0.6 between groups). A1C decreased by -1.03% ± 1.1% from baseline in VP, and by -1.0% ± 1.2% in PP (p = 0.9 between groups). BP, lipid profile, and all other parameters improved in both groups with no significant difference between them. Conclusion: Virtual multidisciplinary ILI is as effective as the in-person intervention program in improving body weight, A1C, BP, and lipid profile, and in reducing the number of anti-hyperglycemic medications. Results from our study suggest that scaling the Why WAIT program in a virtual format to a larger population of patients with diabetes and obesity is feasible and is potentially as successful as the in-person program.

De-escalation of High-flow Respiratory Support for Children Admitted with Bronchiolitis: A Quality Improvement Initiative.

Bronchiolitis is the most common cause for hospitalization in the first year of life, with hypoxemia and acute respiratory failure as major determinants leading to hospitalization. In addition, the lack of existing guidelines for weaning and discontinuing supplemental oxygen, including high-flow nasal cannula, may contribute to prolonged hospitalization and increased resource utilization. Methods: This single-center quality improvement initiative assessed the effect of implementing a standardized care process for weaning and discontinuing high-flow oxygen for patients hospitalized with bronchiolitis. Patients aged 1-24 months with bronchiolitis admitted to the general wards or ICU step-down unit from February 1, 2018, and January 31, 2020 were included in the study. Primary outcomes included length of stay and time on supplemental oxygen, with time on high-flow oxygen and length of time in ICU step-down unit as secondary outcomes. Balancing measures included transfer rate to Pediatric Intensive Care Unit, intubation rate, 7- and 30-day readmission rates, and 7- and 30-day ED visits after discharge. Results: Following the standardized care process implementation, the mean length of stay decreased from 60.7 hours to 46.7 hours (P < 0.01). In addition, the mean time on any supplemental oxygen decreased by 47% (P < 0.01), the mean time on high-flow oxygen decreased by 45% (P < 0.01), and the mean time in the ICU step-down unit decreased by 27% (P =< 0.01). Balancing measures remained unchanged with no statistically significant differences. Conclusion: Implementing a standardized care process for weaning and discontinuing high-flow oxygen may reduce the length of stay and resource utilization for patients hospitalized with bronchiolitis.

The Effects of Perceived Enjoyment of Activities on Cognition in Late-Life.

Objectives: The current cross-sectional study examines the relationship between both frequency and perceived enjoyment of leisure activities and cognitive scores.Methods: We collected self-reported frequency and perceived pleasure of leisure activities from 58 healthy, community-dwelling older adults and administered a battery of cognitive tests, assessing all major domains (i.e., verbal memory, executive functioning, attention, language, and visuospatial ability).Results: Perceived pleasantness or enjoyment of Socializing and Being Effective predicted higher scores on tests of attention, processing speed, and language. Frequency of activity participation in Being Effective and Doing subscales predicted lower scores on executive functioning tasks.Conclusions: The results imply that frequency and perceived enjoyment of some activities are related to cognition in later life.Clinical Implications: Although the frequency of activities is often measured and subsequently used to address mental health and cognitive concerns in late-life (e.g., Behavioral Activation), we discuss the importance for clinicians to formally assess for enjoyment of these activities as well.

Prevalence of and risk factors for non-alcoholic fatty liver disease (NAFLD) and fibrosis among young adults in Egypt.

OBJECTIVE: Limited literature has examined the epidemiology of non-alcoholic fatty liver disease (NAFLD) and fibrosis among young adults in Egypt, a country with one of the highest obesity rates globally. We assessed the prevalence of steatosis and fibrosis among college students in Egypt. DESIGN: In this cross-sectional study, we recruited students unaware of having fatty liver via a call-for-participation at a private university in the Dakahlia governorate of Egypt. Primary outcomes were the prevalence of steatosis as determined by the controlled attenuation parameter component of transient elastography and fibrosis as determined by the liver stiffness measurement component of transient elastography. Secondary outcomes were clinical parameters and socioeconomic factors associated with the presence and severity of steatosis and fibrosis. RESULTS: Of 132 participants evaluated for the study, 120 (91%) were included (median (IQR) age, 20 (19-21) years; 65 (54.2%) female). A total of 38 participants (31.6%) had steatosis, among whom 22 (57.9%) had S3 (severe) steatosis. There was a higher risk for steatosis in persons with overweight (adjusted OR 9.67, 95% CI (2.94 to 31.7, p<0.0001) and obesity (adjusted OR 13.87, 95% CI 4.41 to 43.6, p<0.0001) compared with lean persons. Moreover, higher level of parental education was associated with progressing steatosis stages (S1-S3). Six (5%) participants had transient elastography values equivalent to F2-F3 fibrosis (four with F2 fibrosis (≥7.9 kPa), and two with F3 fibrosis (≥8.8 kPa)). CONCLUSION: In this cohort of college students in Egypt, around 1 in 3 had steatosis, and 1 in 20 had moderate-to-advanced fibrosis, an established risk factor for hepatic and extrahepatic morbidity and mortality. These data underscore the urgency to address the silent epidemic of NAFLD among young adults in the Middle East-North Africa region.

Acute Kidney Injury Among Children Admitted With Viral Rhabdomyolysis.

BACKGROUND: Infectious etiologies cause a large portion of pediatric rhabdomyolysis. Among pediatric patients with rhabdomyolysis, it is unknown who will develop acute kidney injury (AKI). We sought to test the hypothesis that a viral etiology would be associated with less AKI in children admitted with rhabdomyolysis than a nonviral etiology. METHODS: In this single-center retrospective cohort study, patients <21 years of age admitted with acute rhabdomyolysis from May 1, 2010, through December 31, 2018, were studied. The primary outcome was development of AKI, defined by using the Kidney Disease: Improving Global Outcomes guidelines. The primary predictor was identification of viral infection by laboratory testing or clinical diagnosis. Covariates included age, sex, race, insurance provider, presence of proteinuria and myoglobinuria, and initial creatinine kinase and serum urea nitrogen. Routine statistics and multivariable logistic modeling were performed via SAS 9.4 (SAS Institute, Inc, Cary, NC). RESULTS: In total, 319 pediatric patients with rhabdomyolysis were studied. The median age was 13 years. Patients were predominately male (69.9%), non-Hispanic Black (55.2%), and publicly insured (45.1%). We found no difference in the rates of AKI in those with a viral diagnosis versus those without a viral diagnosis (30 of 77 [39.0%] vs 111 of 234 [47.4%]; P = .19). Multivariable analysis revealed that viral diagnosis was not associated with the development of AKI. Patients ≥13 years of age, male patients, and those with proteinuria and elevated serum urea nitrogen on admission had increased odds of developing AKI. CONCLUSIONS: In our study, viral rhabdomyolysis did not have lower rates of AKI compared with nonviral etiologies of AKI; therefore, providers should consider continued caution in these patients.

Dairy Consumption and Cardiometabolic Risk Factors in Patients with Type 2 Diabetes and Overweight or Obesity during Intensive Multidisciplinary Weight Management: A Prospective Observational Study.

Dairy products are integral parts of healthy diets; however, their association with cardiometabolic (CM) health among patients with type 2 diabetes (T2D) undergoing weight management is debated. We examined the relationship between dairy consumption and CM biomarkers in 45 subjects with T2D and obesity (mean age 56 ± 9 yrs, 40% female) enrolled in a 12-week intensive multidisciplinary weight management (IMWM) program. After the IMWM program (intervention phase), subjects were followed for 12 weeks (maintenance phase). We stratified subjects based on initial average dairy consumption into infrequent (IFR), less-frequent (LFR), and frequent (FR) consumers. Outcomes were assessed at baseline, 12, and 24 weeks. There were no differences between tertiles at baseline except for higher total energy intake among FR compared with IFR. HbA1c changes showed no association with dairy consumption at 12 or 24 weeks. FR Females achieved greater weight loss at 12 weeks compared with IFR peers (-4.5 kg; 95%CI: -5.5, -3.5). There was a trend towards lower HDL-C with increasing dairy consumption during the intervention phase. In subjects with T2D and overweight or obesity, dairy consumption during weight management is not associated with HbA1c changes but with lower HDL-C and with higher magnitude of weight loss among females.

Oral GLP1 Analog: Where Does the Tide Go?

T2D is a potentially preventable disease that has been ranked the seventh leading cause of mortality in the United States. There is strong evidence demonstrating that preventing type 2 diabetes is, in many cases, attainable through lifestyle intervention. Unfortunately, prediabetes is mostly overlooked and awareness with diabetes prevention tools is lacking among primary care physicians. Nationally, efforts were not successful in reversing this epidemic even with an array of diabetes medications. Among the most effective medications for T2D are glucagon-like peptide-1 receptor agonists (GLP-1 RAs), which have been shown to reduce both A1C and body weight. Dulaglutide, liraglutide and injectable semaglutide also reduced cardiovascular events and cardiovascular mortality in patients with established cardiovascular disease or multiple cardiovascular risk factors. In this review, we will examine the first FDA approved oral GLP-1 RA; semaglutide. Moreover, this review will discuss the potential impact oral semaglutide may have on glycemic control, weight loss and cardiovascular comorbidities. It also examines the factors that may impact patient compliance, including cost, side effects and clinical issues. Finally, it deliberates the optimism surrounding the development of oral semaglutide in the treatment of diabetes as well as related conditions, such as obesity and non-alcoholic fatty liver disease (NAFLD).

Enhancing the Bioavailability of Silver Through Nanotechnology Approaches Could Overcome Efflux Pump Mediated Silver Resistance in Methicillin Resistant Staphylococcus aureus.

While the wide-spectrum antimicrobial properties and stability of silver nanomaterials have been copiously utilized in many medical and consumer products, we found that Methicillin Resistant Staphylococcus aureus (MRSA) is less susceptible to silver in comparison to Methicillin Sensitive Staphylococcus aureus (MSSA). Pre-exposure of MRSA to sub-lethal concentrations of AgNO3 caused 2.5-fold increase in LD50 of silver suggesting an inducible resistance mechanism. Studies involving gene expression profiling and efflux pump blockers showed the induction of P-type efflux pumps (Cop A, Cop Z and Nor B) as the principle mechanism conferring silver resistance in MRSA. Chlorpromazine-an efflux pump blocker increased sensitivity of MRSA to silver. Leveraging on these observations, silver resistance in MRSA was circumvented by enhancing the bioavailability of silver by cationic functioning of silver nanoparticles or by co-delivering silver together with chlorpromazine. Atomic Force Microscopy showed that poly-ethylene imine (PEI) functionalized silver nanoparticles adhere to bacterial cells which was found to increase the bioavailability, membrane rupture and cell death. The strategy of co-delivery of AgNO3 and chlorpromazine using chitosan-functionalized wormhole silica nanoparticles caused 12 log reduction in bacterial count which was 1000 times higher than bacterial reduction by AgNO3 alone. In short, these studies showed that circumventing antimicrobial resistance in pathogenic bacteria is possible by designed silver nanotechnology.

Contact sport participation and chronic traumatic encephalopathy are associated with altered severity and distribution of cerebral amyloid angiopathy.

Cerebral amyloid angiopathy (CAA) consists of beta-amyloid deposition in the walls of the cerebrovasculature and is commonly associated with Alzheimer's disease (AD). However, the association of CAA with repetitive head impacts (RHI) and with chronic traumatic encephalopathy (CTE) is unknown. We evaluated the relationship between RHI from contact sport participation, CTE, and CAA within a group of deceased contact sport athletes (n = 357), a community-based cohort (n = 209), and an AD cohort from Boston University AD Center (n = 241). Unsupervised hierarchal cluster analysis demonstrated a unique cluster (n = 11) with increased CAA in the leptomeningeal vessels compared to the intracortical vessels (p < 0.001) comprised of participants with significantly greater frequencies of CTE (7/11) and history of RHI. Overall, participants with CTE (n = 251) had more prevalent (p < 0.001) and severe (p = 0.010) CAA within the frontal leptomeningeal vessels compared to intracortical vessels. Compared to those with AD, participants with CTE had more severe CAA in frontal than parietal lobes (p < 0.001) and more severe CAA in leptomeningeal than intracortical vessels (p = 0.002). The overall frequency of CAA in participants with CTE was low, and there was no significant association between contact sport participation and the presence of CAA. However, in those with CAA, a history of contact sports was associated with increased CAA severity in the frontal leptomeningeal vessels (OR = 4.01, 95% CI 2.52-6.38, p < 0.001) adjusting for AD, APOE ε4 status, and age. Participants with CAA had increased levels of sulcal tau pathology and decreased levels of the synaptic marker PSD-95 (p's < 0.05), and CAA was a predictor of dementia (OR = 1.75, 95% CI 1.02-2.99, p = 0.043) adjusting for age, sex, and comorbid pathology. Overall, contact sport participation and CTE were associated with more severe frontal and leptomeningeal CAA, and CAA was independently associated with worse pathological and clinical outcomes.

A young girl with a painful rash.

The speed with which this rash spread and the fact that the patient's skin sloughed off when pressure was applied made the diagnosis clear.

Variation in TMEM106B in chronic traumatic encephalopathy.

The genetic basis of chronic traumatic encephalopathy (CTE) is poorly understood. Variation in transmembrane protein 106B (TMEM106B) has been associated with enhanced neuroinflammation during aging and with TDP-43-related neurodegenerative disease, and rs3173615, a missense coding SNP in TMEM106B, has been implicated as a functional variant in these processes. Neuroinflammation and TDP-43 pathology are prominent features in CTE. The purpose of this study was to determine whether genetic variation in TMEM106B is associated with CTE risk, pathological features, and ante-mortem dementia. Eighty-six deceased male athletes with a history of participation in American football, informant-reported Caucasian, and a positive postmortem diagnosis of CTE without comorbid neurodegenerative disease were genotyped for rs3173615. The minor allele frequency (MAF = 0.42) in participants with CTE did not differ from previously reported neurologically normal controls (MAF = 0.43). However, in a case-only analysis among CTE cases, the minor allele was associated with reduced phosphorylated tau (ptau) pathology in the dorsolateral frontal cortex (DLFC) (AT8 density, odds ratio [OR] of increasing one quartile = 0.42, 95% confidence interval [CI] 0.22-0.79, p = 0.008), reduced neuroinflammation in the DLFC (CD68 density, OR of increasing one quartile = 0.53, 95% CI 0.29-0.98, p = 0.043), and increased synaptic protein density (ß = 0.306, 95% CI 0.065-0.546, p = 0.014). Among CTE cases, TMEM106B minor allele was also associated with reduced ante-mortem dementia (OR = 0.40, 95% CI 0.16-0.99, p = 0.048), but was not associated with TDP-43 pathology. All case-only models were adjusted for age at death and duration of football play. Taken together, variation in TMEM106B may have a protective effect on CTE-related outcomes.

Targeted temperature management in intensive care - Do we let nature take its course?

Should we aim to intervene and control fever in the critically ill patient? The answer is not straightforward and there is certainly no universal agreement on the subject. This article aims to discuss whether we should over-ride nature and disallow it to take it's course, particularly where it appears that this evolutionary response to invading pathogens is actually becoming harmful to the patient. Also discussed here are the physiology of temperature control and the scope of our current understanding of the impact of fever in patients manifesting systemic inflammatory response syndrome (SIRS) and sepsis in ICU, the possible interventions to combat fever (both physical and pharmacological) and the evidence for anti-pyretic drug therapy. The final section examines the potential role of targeted temperature management in the management of sepsis / SIRS in the critically ill.

Differential effect of solar light in increasing the toxicity of silver and titanium dioxide nanoparticles to a fish cell line and zebrafish embryos.

The increasing use of silver (Ag) and titanium dioxide (TiO2) nanoparticles (NPs) in consumer products and their inevitable seepage into the environment prompted us to investigate their potential toxicity to a fish cell line (BF-2) and zebrafish embryos under dark and Simulated Solar Light (SSL) exposure conditions. Using high throughput screening (HTS) platforms, we showed that the oxidative stress-dependent cytotoxicity and embryonic toxicity of NPs were significantly increased upon exposure to SSL. While, the toxicity of TiO2 NPs under SSL exposure could be explained by hydroxyl radical generation, the enhanced toxicity of Ag NPs under SSL exposure was due to surface oxidation and physicochemical modification of Ag NPs and shedding of Ag+, leading to an increased bioavailability of silver. Our observations that solar light could induce physicochemical transformation of TiO2 and Ag NPs and enhance their toxic potential emphasizes the need for conducting future toxicity studies under environmentally relevant exposure conditions to guide decision making on the safe handling of NPs.

Tailored nanostructured titania integrated on titanium micropillars with outstanding wicking properties.

A novel wicking material using nanostructured titania grown on high aspect ratio titanium micropillars is demonstrated. High aspect ratio titanium micropillars were micromachined from bulk titanium sheets. Nanostructured titania was then grown on the surface of titanium micropillars by oxidation in aqueous hydrogen peroxide solution followed by thermal annealing. The nanostructured titania formed has an open porous structure with a nanoscale pore diameter and wall thickness. X-ray diffraction and pole figure studies indicate the formation of anatase phase of titania and the absence of a preferred orientation in the porous film. The hybrid nanostructured titania on titanium micropillars has excellent hydrophilic properties with a water capillary speed comparable to or exceeding that of conventional wick materials commonly used in heat pipes for the thermal management of electronic devices.