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Background: African Americans are at the highest risk of developing heart failure (HF) compared with other races and are hospitalized at 7 to 8 times the rate of Whites. Poor overall self-care, low self-care confidence, and lower levels of perceived social support are factors related to increased risk for hospitalizations in HF. Yet, limited evidence is available regarding the factors that may differentially impact self-care confidence by race in patients with HF., Objective: The aim of this study was to examine to what extent race moderates the relationship between perceived social support and self-care confidence., Method: This is a secondary analysis of cross-sectional data from African American and White patients with HF in North America (n = 429). Patients completed the Multidimensional Scale of Perceived Social Support and the Self-Care Confidence Scale of the Self-Care of Heart Failure Index. A moderation analysis was conducted using hierarchal linear regression., Results: Sample mean age was 60.8 ± 11.5 years, 22.4% were African American, and 54.7% were in New York Heart Association class I or II. Moderation analyses yielded a significant interaction of perceived social support and race, showing White patients, not African Americans, have significantly different self-care confidence scores depending on level of social support: White, b = 0.224, 95% confidence interval [0.046-0.094], t = 5.65, and P < .001; African American, b = -0.776, 95% confidence interval [-0.049 to 0.060], t = 0.212, and P = .832., Conclusions: Our findings show a variable effect of perceived social support on self-care confidence as a function of race, suggesting the need for further research to develop and test interventions tailored to race and levels of social support in HF., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

To date, driver genes for pancreatic cancer treatment are difficult to pursue therapeutically. Targeting mutated KRAS, the most renowned driver gene in pancreatic cancer, is an active area of study. We discovered a gene named SEMA3C was highly expressed in pancreatic cancer cell lines and patients with a G12D mutation in KRAS. High expression of SEMA3C in patients was significantly associated with the decreased survival of pancreatic cancer patients based on the TCGA database. In pancreatic cancer cells, SEMA3C knockdown or inhibition exhibited growth/colony inhibition and cell cycle arrest. In addition, SEMA3C inhibition sensitized KRAS or MEK1/2 inhibition in pancreatic cancer cells. Overexpression of SEMA3C resulted in the induction of autophagy, whereas depletion of SEMA3C compromised induction of autophagy. SEMA3C modified the PD-L1 expression in tumor and immune cells and is correlated with the M2-like macrophage marker ARG1/CD163 expression, which could reshape the tumor microenvironment. Inhibition of SEMA3C decreased tumor formation in the xenograft model in vivo . Taken together, our data suggest that SEMA3C plays a substantial role in promoting cancer cell survival by regulating the autophagy process and impacting the tumor environment immune response. SEMA3C can be used as a novel target or marker with therapeutic or diagnostic potential in pancreatic cancer especially in tumors harboring the specific KRAS G12D mutation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Lindstrom, Kim, Hwang, Hall, Lin and Li.)

Ubiquitin-specific protease 2 (USP2) participates in glucose metabolism in peripheral tissues such as the liver and skeletal muscles. However, the glucoregulatory role of USP2 in the CNS is not well known. In this study, we focus on USP2 in the ventromedial hypothalamus (VMH), which has dominant control over systemic glucose homeostasis. ISH, using a Usp2 -specific probe, showed that Usp2 mRNA is present in VMH neurons, as well as other glucoregulatory nuclei, in the hypothalamus of male mice. Administration of a USP2-selective inhibitor ML364 (20 ng/head), into the VMH elicited a rapid increase in the circulating glucose level in male mice, suggesting USP2 has a suppressive role on glucose mobilization. ML364 treatment also increased serum norepinephrine concentration, whereas it negligibly affected serum levels of insulin and corticosterone. ML364 perturbated mitochondrial oxidative phosphorylation in neural SH-SY5Y cells and subsequently promoted the phosphorylation of AMP-activated protein kinase (AMPK). Consistent with these findings, hypothalamic ML364 treatment stimulated AMPKα phosphorylation in the VMH. Inhibition of hypothalamic AMPK prevented ML364 from increasing serum norepinephrine and blood glucose. Removal of ROS restored the ML364-evoked mitochondrial dysfunction in SH-SY5Y cells and impeded the ML364-induced hypothalamic AMPKα phosphorylation as well as prevented the elevation of serum norepinephrine and blood glucose levels in male mice. These results indicate hypothalamic USP2 attenuates perturbations in blood glucose levels by modifying the ROS-AMPK-sympathetic nerve axis. SIGNIFICANCE STATEMENT Under normal conditions (excluding hyperglycemia or hypoglycemia), blood glucose levels are maintained at a constant level. In this study, we used a mouse model to identify a hypothalamic protease controlling blood glucose levels. Pharmacological inhibition of USP2 in the VMH caused a deviation in blood glucose levels under a nonstressed condition, indicating that USP2 determines the set point of the blood glucose level. Modification of sympathetic nervous activity accounts for the USP2-mediated glucoregulation. Mechanistically, USP2 mitigates the accumulation of ROS in the VMH, resulting in attenuation of the phosphorylation of AMPK. Based on these findings, we uncovered a novel glucoregulatory axis consisting of hypothalamic USP2, ROS, AMPK, and the sympathetic nervous system., (Copyright © 2022 the authors.)

Objective: Care for fear of cancer recurrence (FCR) is considered the most common unmet need among cancer survivors. Yet the prevalence of FCR and predisposing factors remain inconclusive. To support targeted care, we provide a comprehensive overview of the prevalence and severity of FCR among cancer survivors and patients, as measured using the short form of the validated Fear of Cancer Recurrence Inventory (FCRI-SF). We also report on associations between FCR and clinical and demographic characteristics., Methods: This is a systematic review and individual participant data (IPD) meta-analysis on the prevalence of FCR. In the review, we included all studies that used the FCRI-SF with adult (≥18 years) cancer survivors and patients. Date of search: 7 February 2020. Risk of bias was assessed using the Joanna Briggs Institute critical appraisal tool., Results: IPD were requested from 87 unique studies and provided for 46 studies comprising 11,226 participants from 13 countries. 9311 respondents were included for the main analyses. On the FCRI-SF (range 0-36), 58.8% of respondents scored ≥13, 45.1% scored ≥16 and 19.2% scored ≥22. FCR decreased with age and women reported more FCR than men. FCR was found across cancer types and continents and for all time periods since cancer diagnosis., Conclusions: FCR affects a considerable number of cancer survivors and patients. It is therefore important that healthcare providers discuss this issue with their patients and provide treatment when needed. Further research is needed to investigate how best to prevent and treat FCR and to identify other factors associated with FCR. The protocol was prospectively registered (PROSPERO CRD42020142185)., (© 2022 The Authors. Psycho-Oncology published by John Wiley & Sons Ltd.)

Objective: This study evaluated the effects of cerebellar tDCS on motor learning for swallowing., Methods: In a double-blind RCT, 39 healthy adults received either sham, anodal tDCS, or cathodal tDCS in two sessions on two consecutive days. Following 20 min cerebellar tDCS (2 mA) or sham, they underwent swallowing skill training that targeted control of timing and magnitude of submental muscle activation during swallowing. Linear mixed models were used to identify the effects of stimulation on timing and magnitude accuracy as measured by the change in task performance for each training session, and for skill retention on days 3 and 10 post-intervention., Results: Only the sham group had a reduced temporal error from baseline to all following timepoints. When compared to error changes in the sham group, changes from baseline in temporal errors were higher at all timepoints post-intervention for the anodal group, and higher at both retention assessments for the cathodal group. Amplitude errors were smaller for all conditions at all timepoints post-intervention compared to baseline., Conclusions: Cerebellar tDCS was found to inhibit temporal aspects of motor skill learning in swallowing. For the tDCS parameters used in this study, there is no support for use of tDCS to facilitate swallowing rehabilitation. Trial Registry Number (https://www.anzctr.org.au/): ACTRN12615000451505.IMPLICATIONS FOR REHABILITATIONCerebellar tDCS, in combination with motor skill training, has been demonstrated to increase motor skill learning in healthy individuals and neurologically impaired patients.In this study, cerebellar tDCS applied prior to swallowing skill training adversely affected timing measures of submental muscle activation during swallowing.In contrast to published outcomes in the corticospinal literature, both anodal and cathodal tDCS resulted in a relative inhibitory effect on motor skill learning in swallowing when compared to the sham condition.Swallowing skill training without tDCS produced increased accuracy in outcomes.

Introduction: We report the COVID-19 pandemic's impact on health-care use disruption among people with mild cognitive impairment or Alzheimer's disease and related dementia (MCI/ADRD)., Methods: We compared the pandemic-period health-care use between MCI/ADRD and matched non-MCI/ADRD patients. Using 4-year pre-pandemic data, we modeled three health-care use types (inpatient, outpatient, emergency encounters) to predict pandemic-period use, disaggregated for lockdown and post-lockdown periods. Observed health-care use was compared to the predicted. Proportional differences (confidence intervals) are reported., Results: Both MCI/ADRD and non-MCI/ADRD patients ( n  = 5479 each) experienced pandemic-related health-care use disruptions, which were significantly larger for the MCI/ADRD group for outpatient, -13.2% (-16.2%, -10.2%), and inpatient encounters, -12.8% (-18.4%, -7.3%). Large health-care disruptions during lockdown were similar for both groups. However, post-lockdown outpatient, -14.4% (-17.3%, -11.5%), and inpatient, -15.2% (-21.0%, -9.5%), disruptions were significantly greater for MCI/ADRD patients., Conclusion: MCI/ADRD patients experienced greater and sustained pandemic-related health-care use disruptions, highlighting the need for robust strategies to sustain their essential health care during pandemic-like catastrophes., Competing Interests: All authors have no conflicts of interest., (© 2022 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

A wide variety of analytical techniques have been employed for monitoring chemical reactions, with online instrumentation providing additional benefits compared to offline analysis. A challenge in the past for online monitoring has been placement of the monitoring instrumentation as close as possible to the reaction vessel to maximize sampling temporal resolution and preserve sample composition integrity. Furthermore, the ability to sample very small volumes from bench-scale reactions allows the use of small reaction vessels and conservation of expensive reagents. In this study, a compact capillary LC instrument was used for online monitoring of as small as 1 mL total volume of a chemical reaction mixture, with automated sampling of nL-scale volumes directly from the reaction vessel used for analysis. Analyses to demonstrate short term (~2 h) and long term (~ 50 h) reactions were conducted using tandem on-capillary ultraviolet absorbance followed by in-line MS detection or ultraviolet absorbance detection alone, respectively. For both short term and long term reactions (10 and 250 injections, respectively), sampling approaches using syringe pumps minimized the overall sample loss to ~0.2% of the total reaction volume., Competing Interests: Conflict of Interest Statement XX, WRW, and MLL are associated with Axcend Corporation, which is developing and commercializing technology described in this manuscript.

Objectives: The objectives of this study are to: (1) describe communication technology use among paid and unpaid middle-aged and older caregivers of adults 50 and older in a natural (non-experimental) setting; and (2) examine the association between communication technology use, perceived social support, and sense of belonging in this population., Methods: Means and standard deviations, or frequencies and percentages, were used to describe study participants. Chi-square tests or independent sample t -tests were used to compare sociodemographic characteristics, communication technology use, perceived social support, and sense of belonging to the local community between paid and unpaid caregivers. Multivariable regression analysis was performed to predict each outcome (i.e., sense of belonging and social support) based on the use of texting or communication applications., Results: The average age of participants was age 64.2 years, and the majority was female (74.8%) and non-Hispanic White (66.9%). Compared to paid caregivers, unpaid caregivers were older (64.5 vs. 62.2 years, p = 0.022) and a larger proportion were non-Hispanic White (70.8% vs. 47.7%, p < 0.001). Nearly 83% of the study participants reported using texting or communication applications (81.5% among paid caregivers and 83.1% among unpaid caregivers, p = 0.718). After adjusting for caregivers' age, sex, race/ethnicity, and education, a significantly higher sense of belonging was observed among paid caregivers than unpaid caregivers ( b = 9.40, p = 0.009). After adjusting for caregivers' age, sex, race/ethnicity, and education, the use of texting or other communication applications significantly increased caregivers' perceived availability of social support ( b = 0.35, p = 001)., Conclusions: These study results showed a greater sense of belonging to the local community among paid caregivers compared to unpaid caregivers. The use of communication technology was associated with an increased sense of belonging to their local community among paid caregivers, yet the use of communication technology did not contribute to feelings of belonging among unpaid caregivers. In an aging society, both paid and unpaid caregivers are essential elements of the care system. Research is needed to understand the social support needs of paid and unpaid caregivers and the types of interventions to promote social support and community engagement for both groups., Competing Interests: The study was partially supported by Mr. Steve Popovich, the president and CEO of Clairvoyant Network. Clairvoyant Network is a company developing products related to caregiving solutions. Mr. Popovich was not involved in the conceptualization, methodology, analyses, and development of this manuscript. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lee, Ory, Dahlke and Smith.)

Objective: To describe findings, determine the rate of survival to hospital discharge, and identify prognostic indicators of poor outcomes for female cats (queens) with pyometra treated with ovariohysterectomy (OHE) in a nonspecialized setting., Animals: 134 queens with pyometra diagnosed between January 1, 2017, and December 31, 2019., Procedures: The medical records were retrospectively searched and data including patient history, clinical signs, blood work results, and outcome (survival to hospital discharge, length of hospitalization, and uterine rupture) were collected from medical records. Logistic regression models were used to assess potential predictors of outcomes., Results: Dehydration (69% [83/121]) and absolute neutrophilia (83% [52/63]) were commonly reported. The rate of survival to hospital discharge was 100% (126/126; 95% CI, 97% to 100%) for queens treated with OHE; 33% (41/126) were hospitalized ≥ 2 nights, and 4% (5/120) had uterine rupture. Queens with abnormal serum ionized calcium concentration or signs of depressed mentation had greater odds (OR of 4.64 and 2.26, respectively) of ≥ 2 nights' hospitalization. Queens with high rectal temperature, closed pyometra, or heart murmur had greater odds (OR of 35.66, 17.37, or 16.06, respectively) of uterine rupture., Clinical Relevance: Our findings indicated that OHE for pyometra in queens was highly successful even when performed in a nonspecialty hospital with high-quality basic supportive care, and we believe most general practitioners who offer OHE could expect to see similar outcomes. With more general-practice veterinarians comfortable treating pyometra in their clinics, OHE for pyometra will be available to more pets, ultimately saving more lives.

Objective: To determine the rate of survival to hospital discharge and identify indicators associated with poor outcomes among female dogs (bitches) with pyometra treated with ovariohysterectomy (OHE) in a nonspecialized setting., Animals: 405 bitches diagnosed with pyometra at the American Society for the Prevention of Cruelty to Animals Animal Hospital from January 1, 2017, to February 8, 2019., Procedures: For this retrospective study, medical records were searched and data collected including patient history, clinical signs, serum biochemical analyses results, and outcome (survival to hospital discharge, length of hospital stay, and uterine rupture). Logistic regression models were used to assess multivariable associations and identify potential predictive variables., Results: The rate of survival to hospital discharge for bitches with pyometra treated with OHE was 97% (394/405); 44% (174/394) stayed in the hospital ≥ 2 nights, and 3% (11/390) had a ruptured uterus. Bitches with a high BUN concentration or heart murmur had greater odds of death after OHE; however, the model had low predictive power. Those with uterine rupture, inappetence, high concentrations of BUN or serum creatinine, low PCV, or dehydration had greater odds of hospitalization ≥ 2 nights. There were no significant predictors of uterine rupture., Clinical Relevance: The rate of survival to hospital discharge was high for bitches with pyometra treated with OHE in a nonspecialized setting; therefore, general practitioners could expect similar outcomes. With this important procedure widely available in general practices, more pets can receive treatment for this life-threatening disease.

Objective: We have previously reported that 55% of head and neck cancer survivors have neck disability. However, it is unclear what factors contribute to their neck disability. Our study aim is to determine if survivors with neck disability have evidence of cervical spine degenerative disease assessed by computed tomography (CT)., Materials/methods: Cross-sectional analysis of patient-reported neck disability, prospectively collected on survivors of squamous cell carcinomas without recurrence or metastasis over one-year post-treatment. Neck disability and its impact on daily life was measured using the Neck Disability Index (NDI) and compared with cervical CT scans within 6 months. Scans were evaluated for degeneration of the disc and facet of the cervical vertebrae rated on a 5-point scale where 5 indicates more severe disease. Multivariable linear regression was used to analyze the association between NDI and radiographic findings., Results: 116 survivors of oropharyngeal carcinomas were identified, predominantly male (81.9%) with an average age of 62.8 ± 8.2 (range 43.8-81.4). Most survivors had advanced stage III-IVa cancer (94.0%) with treatment modalities including surgery (n=26, 52.0%), chemotherapy ( n = 45, 90.0%), and radiation therapy ( n = 49, 98.0%). Absence of neck disability was observed in 44.0% of survivors, 39.7% had mild disability, and 16.4% moderate disability. The time from treatment to clinic visit was an average of 3.1 ± 2.7 years (range 1.1-13.4). Multivariable analysis of NDI controlling for age, time since treatment, and treatment modality identified an inverse association between NDI and spinal degenerative disease examining cervical discs (-1.46 95% confidence interval (CI) [-2.86, -0.06], p = 0.041) and age (-0.24 95% CI[-0.40, -0.08], p = 0.004)., Conclusions: Our study shows that neck impairment and pain in head and neck cancer survivors is not sufficiently explained by cervical degeneration related to age or trauma, supporting the theory that post-treatment neck disability occurs as a side effect of treatment. These results support the further assessment of structure and function of cervical musculature and degeneration following HNC treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Harris, Branstetter, Li, Piva, Johnson and Nilsen.)

Lipids play a crucial role in the entry and egress of viruses, regardless of whether they are naked or enveloped. Recent evidence shows that lipid involvement in viral infection goes much further. During replication, many viruses rearrange internal lipid membranes to create niches where they replicate and assemble. Because of the close connection between lipids and inflammation, the derangement of lipid metabolism also results in the production of inflammatory stimuli. Due to its pivotal function in the viral life cycle, lipid metabolism has become an area of intense research to understand how viruses seize lipids and to design antiviral drugs targeting lipid pathways. Palmitoylethanolamide (PEA) is a lipid-derived peroxisome proliferator-activated receptor-α (PPAR-α) agonist that also counteracts SARS-CoV-2 entry and its replication. Our work highlights for the first time the antiviral potency of PEA against SARS-CoV-2, exerting its activity by two different mechanisms. First, its binding to the SARS-CoV-2 S protein causes a drop in viral infection of ~70%. We show that this activity is specific for SARS-CoV-2, as it does not prevent infection by VSV or HSV-2, other enveloped viruses that use different glycoproteins and entry receptors to mediate their entry. Second, we show that in infected Huh-7 cells, treatment with PEA dismantles lipid droplets, preventing the usage of these vesicular bodies by SARS-CoV-2 as a source of energy and protection against innate cellular defenses. This is not surprising since PEA activates PPAR-α, a transcription factor that, once activated, generates a cascade of events that leads to the disruption of fatty acid droplets, thereby bringing about lipid droplet degradation through β-oxidation. In conclusion, the present work demonstrates a novel mechanism of action for PEA as a direct and indirect antiviral agent against SARS-CoV-2. This evidence reinforces the notion that treatment with this compound might significantly impact the course of COVID-19. Indeed, considering that the protective effects of PEA in COVID-19 are the current objectives of two clinical trials (NCT04619706 and NCT04568876) and given the relative lack of toxicity of PEA in humans, further preclinical and clinical tests will be needed to fully consider PEA as a promising adjuvant therapy in the current COVID-19 pandemic or against emerging RNA viruses that share the same route of replication as coronaviruses.

Predictable and sustainable engraftment of live biotherapeutic products into the human gut microbiome is being explored as a promising way to modulate the human gut microbiome. We utilize a synbiotic approach pairing the infant gut microbe Bifidobacterium longum subspecies infantis (B. infantis) and human milk oligosaccharides (HMO). B. infantis, which is typically absent in adults, engrafts into healthy adult microbiomes in an HMO-dependent manner at a relative abundance of up to 25% of the bacterial population without antibiotic pretreatment or adverse effects. Corresponding changes in metabolites are detected. Germ-free mice transplanted with dysbiotic human microbiomes also successfully engraft with B. infantis in an HMO-dependent manner, and the synbiotic augments butyrate levels both in this in vivo model and in in vitro cocultures of the synbiotic with specific Firmicutes species. Finally, the synbiotic inhibits the growth of enteropathogens in vitro. Our findings point to a potential safe mechanism for ameliorating dysbioses characteristic of numerous human diseases., Competing Interests: Declaration of interests Prolacta Bioscience employees are also shareholders in the company. D.N.C. served as a consultant to Prolacta Bioscience. A.M.A., A.Y.K., and R.R.J. are members of Prolacta Bioscience’s clinical advisory board. U.S. Patent No. 8,927,027, International Application Pub. No. WO 2021/061991, and their corresponding family member patents and applications are related to this work., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Data on the efficacy of including definitive local therapy to the primary site for head and neck squamous cell carcinoma (HNSCC) patients with synchronous distant metastasis are lacking. In multiple different solid tumor types, there has been benefit when using systemic therapy followed by local consolidative therapy (stereotactic ablative radiotherapy or surgery) directed at metastases. We proposed to retrospectively evaluate patients at our institution that received definitive treatment to the primary., Methods: Single institution retrospective study evaluating 40 patients with metastatic HNSCC treated with definitive surgery (55%) or chemoradiation (45%) to the primary site from 2000 to 2020. The major endpoints were overall survival (OS) and progression-free survival (PFS) for the total population and multiple sub-groups. Some variables were evaluated with multiple covariates Cox model., Results: The median PFS was 8.6 months (95% CI, 6.4-11.6), and OS was 14.2 months (95% CI, 10.9-27.5). In 28% of patients that received induction therapy, there was a twofold increase in median overall survival to 27.5 months. In the 33% of patients that received anti-PD-1 mAb as part of their treatment course, the median OS was significantly increased to 41.7 months (95% CI, 8.7-NR) versus 12.1 months (95% CI, 8.4-14.4) with a 5-year OS of 39%. Multivariate analysis for OS showed significance for age at diagnosis, use of IO, and number of metastatic sites., Conclusion: We observed impressive survival outcomes in metastatic HNSCC patients treated with definitive local therapy to the primary site in addition to induction and/or immunotherapy. Further study is warranted.Level of Evidence: 3., Competing Interests: Dr. Robert L. Ferris, MD, PhD: Aduro Biotech, Inc: Consulting; Astra‐Zeneca/MedImmune: Clinical Trial, Research Funding; Bristol‐Myers Squibb: Advisory Board, Clinical Trial, Research Funding; EMD Serono: Advisory Board; MacroGenics, Inc.: Advisory Board; Merck: Advisory Board, Clinical Trial; Novasenta: Consulting, Stock, Research Funding; Numab Therapeutics AG: Advisory Board; Pfizer: Advisory Board; Tesaro: Research Funding. Dr. Dan Zandberg, MD: Research support (institutional) for role as principal investigator for clinical trials with Merck, Bristol Myers‐Squibb, AstraZeneca, Aduro, ISA Therapeutics, Astelles, Glaxo Smith‐Kline, and Regeneron. All other authors have no conflicts to disclose., (© 2022 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Noble metal nanoparticles have been sought after in cancer nanomedicine during the past two decades, owing to the unique localized surface plasmon resonance that induces strong absorption and scattering properties of the nanoparticles. A popular application of noble metal nanoparticles is photothermal therapy, which destroys cancer cells by heat generated by laser irradiation of the nanoparticles. Gold nanorods have stood out as one of the major types of noble metal nanoparticles for photothermal therapy due to the facile tuning of their optical properties in the tissue penetrative near infrared region, strong photothermal conversion efficiency, and long blood circulation half-life after surface modification with stealthy polymers. In this review, we will summarize the optical properties of gold nanorods and their applications in photothermal therapy. We will also discuss the recent strategies to improve gold nanorod-assisted photothermal therapy through combination with chemotherapy and photodynamic therapy.

Parents of children with ASD who had attended an Australian emergency department (ED; n = 421) completed a questionnaire relating to their experiences in the ED, including (1) child's reason for presentation and existing comorbidities, (2) quality of care during the visit (3) child's behaviour during visit, e.g. sensory responses to the ED environment, and disruptive behaviours. Children with comorbid ASD and intellectual disability were more likely to present with gastrointestinal issues and seizures, while those with comorbid ASD and oppositional defiant disorder were more likely to present with self-injury. ED staff awareness of ASD-related issues, including communication and expression of pain, were common difficulties for parents. The ED environment (e.g. lights, sounds, waiting areas), exacerbated child anxiety and led to disruptive behaviour., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: To determine the glycaemic control and associated factors among patients with type-2 diabetes mellitus on tiered metformin monotherapy over one-year., Methods: Adult Asian patients on metformin monotherapy with tiered dosage up-titration (low < 500 mg/day; medium 500-<1000 mg/day and high ≥ 1000 mg/day) are divided into four sub-cohorts based on their baseline HbA1c < 7%(C <7 ); 7%-<8%(C 7-<8 ); 8%-<9%(C 8-<9 ) and ≥ 9%(C ≥9 ). The HbA1c absolute reduction, time to reach glycaemic control (HbA1c < 7%), and time from glycaemic control to failure (HbA1c ≥ 7%) after the dosage up-titration were the outcomes., Results: Among 5503 eligible patients (mean age = 64.9 years, 45.6% males and 74.6% Chinese), the HbA1c absolute reduction after the up-titration at three months are 0%, 0.4%-0.6%, 0.8%-1.2% and 2.0%-2.1% for C <7, C 7-<8, C 8-<9 and C ≥9 respectively. The median time (months) to attain glycaemic control for low, medium and high dosage up-titration were 4, 3, 3(C 7-<8 ); 12, 7, 4(C 8-<9 ); NA, 7, 7(C ≥9 ). Within twelve months after the goal attainment, 36.2%(C <7 ), 48.8%(C 7-<8 ), 52.7%(C 8-<9 ) and 45.3%(C ≥9 ) of patients had treatment failure., Conclusions: The results show that the baseline HbA1c and tiered metformin dosage up-titration are associated with disproportionate HbA1c reduction, time to glycaemic control and time from glycaemic control to failure., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Family caregivers experience psychological distress or physical strain that may lead to an increased risk of cardiovascular disease (CVD) morbidity and mortality., Objective: This systematic review aimed to describe the current evidence and gaps in the literature on measures used to assess CVD outcomes in family caregivers, the association of caregiving with CVD incidence/risk outcomes, and associated factors in family caregivers of patients with chronic disease., Methods: Medline, PubMed, CINAHL, Web of Science, and Google Scholar were searched for English-language, peer-reviewed studies published from 2008 to 2020 that examined CVD incidence and risk among family caregivers of adults with chronic conditions., Results: Forty-one studies were included in this review. The measures used to assess CVD risk were categorized into biochemical, subclinical markers, components of metabolic syndrome, and global risk scores. Compared with noncaregivers, caregivers were more likely to have higher CVD incidence rates and objectively measured risk. Cardiovascular disease risks were also increased by their caregiving experience, including hours/duration of caregiving, caregivers' poor sleep status, psychological symptoms, poor engagement in physical/leisure activities, and care recipient's disease severity., Conclusions: Although there were limited longitudinal studies in caregivers of patients with diverse health conditions, we found evidence that caregivers are at high risk of CVD. Further research for various caregiver groups using robust methods of measuring CVD risk is needed. Caregiver factors should be considered in developing interventions aimed at reducing CVD risk for caregivers., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The aim was to compare the genetic information of varicose vein patients with that of a healthy population attempting to identify certain significant genetic associations., Method: Patients' clinical characteristics and demographics were collected, and their genetic samples were examined. The results were compared to the genetic information of one thousand sex-matched healthy controls from Taiwan Biobank database. The Clinical-Etiology-Anatomy-Pathophysiology classification was applied for further subgroup analysis., Results: After comparison of genetic information of ninety-six patients to that of healthy controls, two significant single nucleotide polymorphisms (SNPs) were identified. One was in DPYSL2 gene, and the other was in VSTM2L gene. A further comparison between C2-3 patient subgroup and C4-6 subgroup identified another four significant SNPs, which were located in ZNF664-FAM101A, PHF2, ACOT11, and TOM1L1 genes., Conclusion: Our preliminary result identified six significant SNPs located in six different genes. All of them and their genetic products may warrant further investigations.

Aim: Households are a significant venue for the transmission of SARS-CoV-2. We conducted a study to characterise the transmission dynamics and identify risk factors for household transmission of SARS-CoV-2 in Negeri Sembilan, Malaysia., Methods: This retrospective observational study included 185 families of paediatric COVID-19 cases from 1 February 2020 to 31 December 2020. We identified the index case for each household and gathered the socio-demographic, epidemiological investigation results and risk factors for household transmission from medical case records. The secondary attack rate was calculated, and logistic regression analyses were used to identify risk factors associated with secondary household transmission of SARS-CoV-2., Results: Of the 848 household contacts, 466 acquired secondary infections, resulting in a secondary attack rate of 55%. The median age of the secondary cases was 12 years. Female household contacts and household contacts who slept in the same room with the index case were significantly associated with increased risk for COVID-19. Other independent risk factors associated with higher transmission risk in the household included an index case who was symptomatic, a household index case aged greater than 18 years and a male household index case., Conclusions: High rates of household transmission of COVID-19 were found, indicating households were a major setting of transmission of SARS-CoV-2. Our data provide insight into the risk factors for household transmission of SARS-CoV-2 in Malaysia., (© 2021 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Background: Pulmonary arterial hypertension (PAH) increases right ventricular (RV) workload and decreases myocardial oxygen reserve, eventually leading to poor cardiac output. This study created and assessed a novel model of RV work output based on RV hemodynamics and oxygen supply, allowing new insight into causal mechanisms of RV dysfunction., Methods: The RV function model was built upon an earlier, left ventricular model and further adjusted for more accurate clinical use. The model assumes that RV total power output (1) is the sum of isovolumic and stroke power and (2) is linearly related to its right coronary artery oxygen supply. Thus, when right coronary artery flow is limited or isovolumic power is elevated, less energy is available for producing cardiac output. The original and adjusted models were validated via data from patients with idiopathic PAH (n = 14) and large animals (n = 6) that underwent acute pulmonary banding with or without hypoxia., Results: Both models demonstrated strong, significant correlations between RV oxygen consumption rate and RV total power output for PAH patients (original model, R 2  = 0.66; adjusted model, R 2  = 0.78) and sheep (original, R 2  = 0.85; adjusted, R 2  = 0.86). Furthermore, the models demonstrate a significant inverse relationship between required oxygen consumption and RV efficiency (stroke power/total power) (p < 0.001). Lastly, higher NYHA class was indicative of lower RV efficiency and higher oxygen consumption (p = 0.013)., Conclusion: Right ventricular total power output can be accurately estimated directly from pulmonary hemodynamics and right coronary perfusion during PAH. This model highlights the increased vulnerability of PAH patients with compromised right coronary flow coupled with high afterload., (© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background: The use of ultrasound as an adjunct to clinical swallowing evaluation provides quantitative physiological and morphological data. As a low-risk procedure, ultrasound imaging can be performed outside of a medical setting. This is particularly important for patients living in rural areas with restricted access to a hospital. Technical advances have produced pocket-sized ultrasound technology that is more affordable, and therefore within the fiscal reach of most allied health services., Aims: To explore the validity and reliability of pocket-sized ultrasound technology in dysphagia assessment., Methods & Procedures: Data were acquired from 43 patients with dysphagia using the Clarius ultrasound device. Ultrasound and videofluoroscopic measures of hyoid and laryngeal displacement during liquid and puree swallowing were collected concurrently to quantify correlation and agreement between identical measures derived from the two instruments. Reliability of ultrasound was assessed for measures of hyoid and laryngeal displacement, tongue thickness, and size of the submental muscles in eight patients. Reliability was evaluated for the entire process of data acquisition including scanning and online measurement using an iPad in a clinical setting and for offline measurement on a computer screen to explore environmental influences on reliability., Outcomes & Results: Results revealed poor correlation between the measures of interest across instruments. Reliability of the entire process of data acquisition in a clinical setting was insufficient while reliability was more promising for offline measurements., Conclusions & Implications: The clinical use of pocket-sized ultrasound devices, such as the Clarius system, for swallowing evaluation is not indicated at this time. Enhanced validity and reliability of the entire process of data acquisition are needed prior to clinical translation of such technology., What This Paper Adds: What is already known on the subject The use of ultrasound allows for radiation-free, non-invasive swallowing assessment. Some data suggest that ultrasound is valid and reliable in the evaluation of swallowing using standard-sized equipment. Insufficient validity and reliability have been reported for pocket-sized ultrasound technology in the assessment of healthy swallowing. What this paper adds to existing knowledge This research is the first to provide validity and reliability data of the pocket-sized Clarius technology in the evaluation of swallowing in patients with dysphagia. Insufficient validity and reliability of online data acquisition in a clinical environment were found. Reliability for offline measurement was more promising. What are the potential or actual clinical implications of this work? The clinical use of pocket-sized ultrasound devices, such as the Clarius system, for swallowing assessment is not indicated at this time., (© 2022 The Authors. International Journal of Language & Communication Disorders published by John Wiley & Sons Ltd on behalf of Royal College of Speech and Language Therapists.)

Introduction: Delayed hypopituitarism is the most common complication after stereotactic radiosurgery (SRS) for pituitary adenomas. The aim of this study was to investigate the relationship between the distance from the hypothalamic-pituitary axis to the treatment target and anterior pituitary function preservation after SRS., Methods: Between 2007 and 2020, consecutive adult patients who underwent single-session SRS for non-functioning or hormone-secreting pituitary adenomas with ≥ 6 months of follow-up were included. Distance measurements between hypothalamic-pituitary axis structures and the SRS target volume were quantified on MRI. The primary outcome was anterior pituitary function preservation. Outcomes were compared using multivariable regression and area under the receiver operator characteristic curve (AUROC) analyses., Results: The study cohort comprised 224 patients, who were categorized by preservation (n = 168) and no preservation (n = 56) of anterior pituitary function after SRS. The mean and median clinical follow-up durations were 53.7 (38.0) and 46.0 (17.0-75.0) months, respectively. Independent predictors of anterior pituitary function preservation were a greater distance between the center of the pituitary gland and center of the SRS target [OR 1.101 (1.000-1.213), p = 0.050], and a shorter clinical follow-up duration [OR 0.985 (0.977-0.993), p < 0.0001]. The adjusted AUROC for the distance from the center of the pituitary gland and center of the SRS target in predicting anterior pituitary function preservation was 0.595. The sensitivity, specificity, positive predictive value and negative predictive value in predicting anterior pituitary function preservation at the optimal cut-off distance of 15 mm were 30.0, 88.0, 89.9 and 26.2%, respectively., Conclusions: Greater distance between the normal pituitary gland and the SRS target is associated with anterior pituitary function preservation and increasing this distance should be a goal of adenoma resection. Larger prospective, multi-center studies are necessary to corroborate this finding and establish the effects of distance on hypopituitarism after SRS for pituitary adenomas., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: We aimed to determine the feasibility and efficacy of online strategies to recruit parents of children with pediatric rheumatic diseases (PRDs) for research and to evaluate the degree to which known features of various rheumatic disease groups were present in the online cohort., Methods: We studied two cohorts; the first was composed of respondents from a cross-sectional parental survey of children with PRDs contacted through patient support groups and social media platforms, and the second cohort was composed of participants from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) legacy clinical registry., Results: In the social media cohort, 712 complete surveys were analyzed. Most (65.9%) were referred from Facebook. The most common rheumatic disease was juvenile idiopathic arthritis (JIA) (27.1%), followed by juvenile dermatomyositis (22.1%). In the CARRA registry cohort, 7985 records were included. JIA was the largest disease group (70.3%), followed by systemic lupus erythematosus (12.0%). The age at disease onset for most PRDs was similar between those in the social media and CARRA registry cohorts (mean difference = 1.3 years)., Conclusion: Recruitment through Facebook was the most fruitful. The clinical characteristics of the social media cohort were similar to those of patients recruited through a clinical registry, suggesting the utility of online recruitment for engaging disease-relevant cohorts. Parents of children with rare PRDs were overrepresented in the social media cohort, perhaps reflecting the increased need of those parents to find online information and receive emotional support. Social media recruitment for research studies may help expand the number and diversity of participants in clinical research, especially by including those with rare diseases., (© 2022 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Spontaneous coronary artery dissection (SCAD) is a potential precipitant of myocardial infarction and sudden death for which the etiology is poorly understood. Mendelian vascular and connective tissue disorders underlying thoracic aortic disease (TAD), have been reported in ~5% of individuals with SCAD. We therefore hypothesized that patients with TAD are at elevated risk for SCAD. We queried registries enrolling patients with TAD to define the incidence of SCAD. Of 7568 individuals enrolled, 11 (0.15%) were found to have SCAD. Of the sequenced cases (9/11), pathogenic variants were identified (N = 9), including COL3A1 (N = 3), FBN1 (N = 2), TGFBR2 (N = 2), TGFBR1 (N = 1), and PRKG1 (N = 1). Individuals with SCAD had an increased frequency of iliac artery dissection (25.0% vs. 5.1%, p = 0.047). The prevalence of SCAD among individuals with TAD is low. The identification of pathogenic variants in genes previously described in individuals with SCAD, particularly those underlying vascular Ehlers-Danlos, Marfan syndrome, and Loeys-Dietz syndrome, is consistent with prior reports from clinical SCAD series. Further research is needed to identify specific genetic influences on SCAD risk., (© 2022 Wiley Periodicals LLC.)

Multinational studies have reported monogenic etiologies in 25%-30% of children with steroid-resistant nephrotic syndrome. Such large studies are lacking in Asia. We established Deciphering Diversities: Renal Asian Genetics Network (DRAGoN) and aimed to describe the genetic and clinical spectrums in Asians. We prospectively studied a cohort of 183 probands with suspected genetic glomerulopathies from South and Southeast Asia, of whom 17% had positive family history. Using multi-gene panel sequencing, we detected pathogenic variants in 26 (14%) probands, of whom one-third had COL4A4 or COL4A5 variants (n = 9, 5%). Of those with COL4A5 defects, only 25% had features suggestive of Alport syndrome. Besides traditional predictors for genetic disease (positive family history and extrarenal malformations), we identified novel predictors, namely older age (6.2 vs. 2.4 years; p = 0.001), hematuria (OR 5.6; 95% CI 2.1-14.8; p < 0.001), and proteinuria in the absence of nephrotic syndrome (OR 4.6; 95% CI 1.8-11.8; p = 0.001) at first manifestation. Among patients who first presented with proteinuria without nephrotic syndrome, the genetic diagnostic rates were >60% when a second risk factor (positive family history or extrarenal manifestation) co-existed. The genetic spectrum of glomerulopathies appears different in Asia. Collagen IV genes may be included in sequencing panels even when suggestive clinical features are absent., (© 2022 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Current best practices in tumor registries provide a glimpse into a limited time frame over the natural history of disease, usually a narrow window around diagnosis and biopsy. This creates challenges meeting public health and healthcare reimbursement policies that increasingly require robust documentation of long-term clinical trajectories, quality of life, and health economics outcomes. These challenges are amplified for underrepresented minority (URM) and other disadvantaged populations, who tend to view the institution of clinical research with skepticism. Participation gaps leave such populations underrepresented in clinical research and, importantly, in policy decisions about treatment choices and reimbursement, thus further augmenting health, social, and economic disparities. Cloud computing, mobile computing, digital ledgers, tokenization, and artificial intelligence technologies are powerful tools that promise to enhance longitudinal patient engagement across the natural history of disease. These tools also promise to enhance engagement by giving participants agency over their data and addressing a major impediment to research participation. This will only occur if these tools are available for use with all patients. Distributed ledger technologies (specifically blockchain) converge these tools and offer a significant element of trust that can be used to engage URM populations more substantively in clinical research. This is a crucial step toward linking composite cohorts for training and optimization of the artificial intelligence tools for enhancing public health in the future. The parameters of an idealized clinical genomic registry are presented.

Literature suggests that anxiety affects gait and balance among young adults. However, previous studies using machine learning (ML) have only used gait to identify individuals who report feeling anxious. Therefore, the purpose of this study was to identify individuals who report feeling anxious at that time using a combination of gait and quiet balance ML. Using a cross-sectional design, participants (n = 88) completed the Profile of Mood Survey-Short Form (POMS-SF) to measure current feelings of anxiety and were then asked to complete a modified Clinical Test for Sensory Interaction in Balance (mCTSIB) and a two-minute walk around a 6 m track while wearing nine APDM mobility sensors. Results from our study finds that Random Forest classifiers had the highest median accuracy rate (75%) and the five top features for identifying anxious individuals were all gait parameters (turn angles, variance in neck, lumbar rotation, lumbar movement in the sagittal plane, and arm movement). Post-hoc analyses suggest that individuals who reported feeling anxious also walked using gait patterns most similar to older individuals who are fearful of falling. Additionally, we find that individuals who are anxious also had less postural stability when they had visual input; however, these individuals had less movement during postural sway when visual input was removed.

During photon upconversion, quantum dots (QDs) transfer energy to molecules in solution through a long ligand shell. This insulating ligand shell imparts colloidal stability at the expense of efficient photosensitization. For the first time, we quantify the barrier these aliphatic ligands pose for triplet energy transfer in solution. Using transient absorption spectroscopy, we experimentally measure a small damping coefficient of 0.027 Å -1 for a ligand exceeding 10 carbons in length. The dynamic nature of ligands in solution lowers the barrier to charge or energy transfer compared to organic thin films. In addition, we show that surface ligands shorter than 8 carbons in length allow direct energy transfer from the QD, bypassing the need for a transmitter ligand to mediate energy transfer, leading to a 6.9% upconversion quantum yield compared with 0.01% for ligands with 18 carbons. This experimentally derived insight will enable the design of efficient QD-based photosensitizers for catalysis and energy conversion.

There is a continued need to identify novel therapeutic targets to prevent the mortality associated with prostate cancer. In this context, mitochondrial Rho GTPase 2 (MIRO2) mRNA was upregulated in metastatic prostate cancer compared with localized tumors, and higher MIRO2 levels were correlated with poor patient survival. Using human cell lines that represent androgen-independent or -sensitive prostate cancer, we showed that MIRO2 depletion impaired cell growth, colony formation, and tumor growth in mice. Network analysis of MIRO2's binding partners identified metabolism and cellular responses to extracellular stimuli as top overrepresented pathways. The top hit on our screen, General Control Nonderepressible 1 (GCN1), was overexpressed in prostate cancer, and interacted with MIRO2 in prostate cancer cell lines and in primary prostate cancer cells. Functional analysis of MIRO2 mutations present in patients with prostate cancer led to the identification of MIRO2 159L, which increased GCN1 binding. Importantly, MIRO2 was necessary for efficient GCN1-mediated GCN2 kinase signaling and induction of the transcription factor activating transcription factor 4 (ATF4) levels. Further, MIRO2's effect on regulating prostate cancer cell growth was mediated by ATF4. Finally, levels of activated GCN2 and ATF4 were correlated with MIRO2 expression in prostate cancer xenografts. Both MIRO2 and activated GCN2 levels were higher in hypoxic areas of prostate cancer xenografts. Overall, we propose that targeting the MIRO2-GCN1 axis may be a valuable strategy to halt prostate cancer growth., Implications: MIRO2/GCN1/GCN2 constitute a novel mitochondrial signaling pathway that controls androgen-independent and androgen-sensitive prostate cancer cell growth., (©2022 The Authors; Published by the American Association for Cancer Research.)

Activity limitations can diminish life satisfaction. This study explored the role of optimism on the relationship between changes in activities of daily living and instrumental activities of daily living (ADL/IADL) limitations and life satisfaction over time among middle-aged and older adults. Growth curve modeling accounting for intra- and inter-individual changes in life satisfaction was applied to the 2008-2018 waves of the Health and Retirement Study Leave Behind Survey subsample ( n = 39,122 person-years). After controlling for sociodemographic factors, physical functioning decline adversely affected life satisfaction ( β ADL = -0.12, β IADL = -0.13, p < 0.001), but the negative consequences reduced slightly through optimism ( β ADL = -0.11, β IADL = -0.12, β optimism = 0.47, p < 0.001). Increasing optimism could reduce the negative consequences of ADL/IADL limitations on life satisfaction among middle-aged to older adults.

The effortful swallowing technique aims to compensate for or rehabilitate impaired swallowing by using maximal volitional effort to behaviorally modify aspects of swallowing physiology. Given that swallowing is a submaximal task, swallowing at submaximal levels has recently been suggested as a more task-specific therapeutic technique. The aim of this study was to investigate differences in muscle activity during minimum, regular, and maximum effort swallowing of different boluses and across different ages, with the goal of characterizing the task specificity of minimum effort and maximum effort swallowing. Forty-three healthy adults (22 female) representing four age groups (20-39, 40-59, 60-79, and 80 + years) participated in the study. They were verbally cued to swallow saliva and 5 mL water boluses using participant-determined minimum, regular, and maximum levels of effort, in randomized order. sEMG peak amplitude and duration of each swallow were measured. Linear mixed effects analyses demonstrated that compared to regular effort swallowing, maximum effort swallowing resulted in increased sEMG amplitude (p < .001) and prolonged duration (p < .001), while minimum effort swallowing resulted in decreased amplitude (p < .001) but no significant difference in duration (p = .06). These effects occurred regardless of age or bolus type. Differences in sEMG activity were smaller between regular and minimum effort swallowing than regular and maximum effort swallowing. Both increasing and decreasing volitional efforts during swallowing translate to significant modulation of muscle activity. However, regular swallowing is more similar to minimal effort swallowing. Results reinforce the concept of swallowing as a submaximal task, and provide insight into the development of sEMG biofeedback techniques for rehabilitation., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: We aim to (1) determine the prevalence and predictors of trismus and (2) examine the relationship of trismus, swallowing dysfunction, and quality of life (QOL) in survivors of head and neck cancer (HNC)., Study Design: Case series with chart review., Setting: Multidisciplinary HNC survivorship clinic., Methods: Data on trismus and patient-reported outcomes were obtained from survivors of HNC between December 2016 and October 2019. Trismus was defined as a maximum interincisal opening ≤35 mm. QOL and swallowing dysfunction were measured with the University of Washington Quality of Life questionnaire and EAT-10 (Eating Assessment Tool-10), respectively. Linear regressions were applied to investigate the relationship of trismus with QOL and swallowing dysfunction., Results: Of the 237 survivors, 22.78% (n = 54) had trismus. Advanced stage of cancer (stage III/IV vs Tis-II, P = .002) and treatment (nonsurgical and surgery + adjuvant treatment vs surgery only, P = .006) were correlated with a higher prevalence of trismus. After controlling for cancer stage and treatment type, EAT-10 scores for survivors with trismus were 9.342 (95% CI, 6.262-12.423; P < .0001) higher than those without trismus. The University of Washington Quality of Life Physical and Social-Emotional subscales for patients with trismus were 14.088 (95% CI, 9.042-19.134; P < .0001) and 10.470 (95% CI, 4.793-16.147; P = .0003) lower than those without trismus, respectively., Conclusion: Trismus is a common, treatment-related consequence and is associated with increased symptoms of dysphagia and decreased QOL. Early detection and management of trismus in survivors of HNC are essential to optimize QOL and reduce morbidity.

Purpose: In Cushing disease, early post-operative serum cortisol fluctuations have not been adequately characterized, and their association with initial remission and recurrence is unclear., Methods: A retrospective cohort study of patients with Cushing disease was conducted at two institutions. A "riser" was defined a priori as a paradoxical increase in serum cortisol with an immediate incremental increase in serum cortisol over three consecutive cortisol draws separated by roughly 6-h (definition 1). Post hoc analyses used a definition of two consecutive increases (definition 2). Risers were compared to non-risers for initial remission and time-to-recurrence., Results: A total of 505 patients with Cushing disease were screened, and 469 had adequate data for group assignment. Analysis of post-operative cortisol showed a subgroup of "risers" with a frequency of 3.6% for definition 1 and 42.6% for definition 2. In these patients, cortisol levels were significantly higher until approximately 36 h post-operatively, and cortisol had a significantly longer mean serum half-life. In the post hoc analysis, definition 2 risers had a lower remission rate compared to non-risers (162/196, 82.7%, versus 243/264, 92.0%) with an odds ratio of 0.41 (0.23-0.73; p = 0.003). For both definitions, recurrence was similar between groups., Conclusions: We found that almost half of Cushing disease patients experienced a temporary increase in serum cortisol level during the early post-operative period. Serum cortisol half-life was longer, and the remission rates were lower, however, recurrence rates were similar to non-risers., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

There is an increased interest in the use of personalized medicine approaches in the prevention or treatment of obesity, however, few studies have used these approaches to identify individual differences in treatment effects. The current study demonstrates the use of the predicted individual treatment effects framework to test for individual differences in the effects of the ACTION-PAC intervention, which targeted the treatment and prevention of obesity in a high school setting. We show how methods for personalized medicine can be used to test for significant individual differences in responses to an intervention and we discuss the potential and limitations of these methods. In our example, 25% of students in the preventive intervention, were predicted to have their BMI z-score reduced by 0.39 or greater, while at other end of the spectrum, 25% were predicted to have their BMI z-score increased by 0.09 or more. In this paper, we demonstrate and discuss the process of using methods for personalized medicine with interventions targeting adiposity and discuss the lessons learned from this application. Ultimately, these methods have the potential to be useful for clinicians and clients in choosing between treatment options, however they are limited in their ability to help researchers understand the mechanisms underlying these predictions., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Middle-aged and older men of color with chronic conditions have low utilization of preventive health services. In the context of the Chronic Care Model (CCM), the objective of this study was to identify perceptions about being informed, activated patients and having productive interactions in healthcare settings among non-Hispanic Black and Hispanic middle-aged and older men with chronic health conditions in the United States. Using an internet-based survey deployed nationally using a Qualtrics panel, data were collected from a sample of non-Hispanic Black and Hispanic men aged 40 years and older with one or more self-reported chronic conditions ( n = 2028). Chi-square tests and one-way ANOVAs were used to describe this national sample by race/ethnicity and age group (40-64 years and ≥65 years). Results suggest that most health-related factors differed more on age than by race/ethnicity. Younger age groups reported less preventive care, greater barriers to self-care, mental health issues, and risky behavior. Findings from this study provide insight into the health status and healthcare utilization of racial/ethnic men with one or more chronic conditions. Results may help inform prevention and treatment interventions for middle-aged and older men of color.

In this paper, tungsten oxide (WO 3 ) is deposited on a silicon substrate applied in electrolyte-insulator-semiconductor structures for pH sensing devices. To boost the sensing performance, yttrium (Y) is doped into WO 3 membranes, and annealing is incorporated in the fabrication process. To investigate the effects of Y doping and annealing, multiple material characterizations including X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), atom force microscopy (AFM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) are performed. Material analysis results indicate that annealing and Y doping can increase crystallinity, suppress defects, and enhance grainization, thereby strengthening membrane sensing capabilities in terms of sensitivity, linearity, and reliability. Because of their stable response, high reliability, and compact size, Y-doped WO 3 membranes are promising for future biomedical applications.

This study examined metropolitan and rural differences regarding concerns about opioid misuse and support for different strategies to reduce opioid use disorder risk in areas not designated as high-risk. This study used cross-sectional data from a regional community health assessment, which was collected in 2019 using a combination of stratified random sampling and clinic-based purposive sampling in Central Texas. The secondary data included 430 and 270 respondents from metropolitan and rural (not metropolitan) counties, respectively. The primary outcomes were perceived concern about the opioid crisis, perceived likelihood of getting addiction treatment, and support for strategies to reduce opioid use disorder risks. Multiple multivariable regression models were used to examine metropolitan and rural differences in the outcome variables after adjusting for age, sex, ethnicity, race, marital status, education, and household income. Respondents were about 58 years old on average. A majority were female (60%), non-Hispanic (88%), and White (83%). About 60% of rural and metropolitan respondents were concerned about opioid use and misuse in their community. After adjusting for respondents' demographic characteristics, rural respondents were significantly less likely to perceive that individuals are getting the needed opioid use disorder treatment (aOR = 0.69, P  = 0.031). Rural respondents were also significantly less supportive for legalizing syringe service programs in their communities (aOR = 0.71, P  = 0.044) than metropolitan respondents. Differing attitudes by respondents from metropolitan and rural areas indicate the importance of tailoring prevention and mitigation efforts to address opioid use disorder in advance of an impending public health crisis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier Inc.)

Chronic disease self-management education (CDSME) programs benefit individuals with chronic diseases, including mental health conditions, by improving health-related outcomes and increasing engagement with the health care system. Recruiting individuals with a history of mental health conditions to participate in CDSME is challenging, particularly in rural, underserved areas. Hence, it is important to understand factors associated with the presence of mental health conditions, and impacts of CDSME on patient engagement. This project identifies individual and program-level characteristics, as well as recruitment characteristics, associated with reporting a history of depression and/or anxiety. It also assesses factors related to program engagement and the relationship between completing CDSME and patient activation. Data were collected during CDSME workshops offered in 2019 in a rural region of New York. Of the 421 enrollees who completed survey instruments, 162 reported a history of depression and/or anxiety. Univariate analyses indicated that those reporting a history of depression and/or anxiety were younger, female, in poorer health, had more comorbidities, were Medicaid beneficiaries, and had lower patient activation scores. They also heard about and signed up for the workshop through the internet at higher rates than those not reporting a history of depression and/or anxiety. Multivariable logistic regression modeling indicated age, self-rated health, and number of comorbidities were independent predictors of reporting a history of depression and/or anxiety. Among CDSME completers, patient activation significantly improved regardless of history of depression and/or anxiety. Engaging individuals with mental health conditions in CDSME requires a multimodal recruitment strategy incorporating electronic marketing and registration., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Background: Parkinson's disease (PD) is a neurodegenerative disorder characterized by a combination of motor and non-motor dysfunction. Dysphagia is a common symptom in PD, though it is still too frequently underdiagnosed. Consensus is lacking on screening, diagnosis, and prognosis of dysphagia in PD., Objective: To systematically review the literature and to define consensus statements on the screening and the diagnosis of dysphagia in PD, as well as on the impact of dysphagia on the prognosis and quality of life (QoL) of PD patients., Methods: A multinational group of experts in the field of neurogenic dysphagia and/or PD conducted a systematic revision of the literature published since January 1990 to February 2021 and reported the results according to PRISMA guidelines. The output of the research was then analyzed and discussed in a consensus conference convened in Pavia, Italy, where the consensus statements were drafted. The final version of statements was subsequently achieved by e-mail consensus., Results: Eighty-five papers were used to inform the Panel's statements even though most of them were of Class IV quality. The statements tackled four main areas: (1) screening of dysphagia: timing and tools; (2) diagnosis of dysphagia: clinical and instrumental detection, severity assessment; (3) dysphagia and QoL: impact and assessment; (4) prognostic value of dysphagia; impact on the outcome and role of associated conditions., Conclusions: The statements elaborated by the Consensus Panel provide a framework to guide the neurologist in the timely detection and accurate diagnosis of dysphagia in PD., (© 2021. The Author(s).)

In drug discovery, partition and distribution coefficients, logP and logD for octanol/water, are widely used as metrics of the lipophilicity of molecules, which in turn have a strong influence on the bioactivity and bioavailability of potential drugs. There are a variety of established methods, mostly fragment or atom-based, to calculate logP while logD prediction generally relies on calculated logP and pKa for the estimation of neutral and ionized populations at a given pH. Algorithms such as ClogP have limitations generally leading to systematic errors for chemically related molecules while pKa estimation is generally more difficult due to the interplay of electronic, inductive and conjugation effects for ionizable moieties. We propose an integrated machine learning QSAR modeling approach to predict logD by training the model with experimental data while using ClogP and pKa predicted by commercial software as model descriptors. By optimizing the loss function for the ClogD calculated by the software, we build a correction model that incorporates both descriptors from the software and available experimental logD data. Additionally, we calculate logP from the logD model using the software predicted pKa's. Here, we have trained models using publicly or commercial available logD data to show that this approach can improve on commercial software predictions of lipophilicity. When applied to other logD data sets, this approach extends the domain of applicability of logD and logP predictions over commercial software. Performance of these models favorably compare with models built with a larger set of proprietary logD data., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Current conceptualizations of patient self-advocacy focus on women with cancer, leaving knowledge of male self-advocacy deficient. The purpose of this study is to describe the key components of self-advocacy among men with cancer. Adult (≥18 years old) men with a history of invasive cancer were recruited from cancer clinics and registries. Trained researchers led individual semi-structured interviews regarding participants' challenges, how they overcame those challenges, and barriers and facilitators to their self-advocacy. All interviews were analyzed using descriptive content analysis methods and synthesized into major themes. These themes were refined after receiving feedback from key stakeholders. Participants (N = 28) reported three major self-advocacy themes: (i) managing through information and planning; (ii) finding the best team and falling in line; and (iii) strategic social connections. These themes are richly described with representative quotations for each theme and subtheme. Based on these findings, existing models of patient self-advocacy should be adjusted to encompass how men self-advocate. Clinicians should consider how gender may impact how and why patients with cancer self-advocate so that they can best support their patients in achieving patient-centered care., (© 2021 John Wiley & Sons Australia, Ltd.)

There is no identified risk-free threshold exposure to asbestos. Based on epidemiology and toxicology, asbestos fiber dimensions have been implicated in causing asbestos-related diseases. Phase-contrast microscopy provides only a limited index of exposure to fiber dimensions implicated in mesothelioma induction. Installed asbestos-containing materials (ACMs) create an ongoing risk of intense exposure during natural disasters and remodeling, along with low-level exposure arising from the continual emission of airborne asbestos into the environment arising from weathering of installed ACM. Epidemiological studies have demonstrated a risk of disease associated with proximity to asbestos cement roofing (ACR), while ongoing environmental emissions of asbestos from installed ACR have also been demonstrated. Owing to the limitations of the available data, a precautionary approach is warranted; asbestos-free roofing materials should be used in new construction and existing ACR should be removed at the earliest opportunity., (© 2021 The Authors. American Journal of Industrial Medicine Published by Wiley Periodicals LLC.)

A new marine planktonic ciliate from Taiwan, Strombidium parasulcatum sp. n., is described based on live observations, protargol staining, and molecular data. Its morphological characters are similar to those of Strombidium sulcatum Claparède and Lachmann, 1859 sensu Song et al., 2000 but differ from S. sulcatum sensu Fauré-Fremiet, 1912 and sensu Fauré-Fremiet and Ganier, 1970 by several morphological characters. The 18S rRNA gene sequences of the two forms display 76 base pair differences (about 5%), indicating that they should be considered separate species. The highest observed specific growth rates of S. parasulcatum in culture were 1.79 day -1 over 1 day and 1.52 day -1 over 2 days, both starting at day 5. Bacteria appear to be an important food resource for the cultivation of this medium-sized oligotrich ciliate. This and other recent studies suggest that cryptic species may be common in the genus Strombidium , and an integrative approach including morphological, ecological, and molecular data should be used to address this question., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tsai, Lee and Chiang.)