Patient Preferences for Benefit and Risk Associated With High Intensity Focused Ultrasound for the Ablation of Prostate Tissue in Men With Localized Prostate Cancer.

INTRODUCTION: Food and Drug Administration must make decisions about emerging high intensity focused ultrasound (HIFU) devices that may lack relevant clinical oncologic data but present with known side effects. This study aims to capture patients' perspective by quantifying their preferences regarding the available benefit and important side effects associated with HIFU for localized prostate cancer. MATERIALS AND METHODS: Preferences for HIFU outcomes were examined using a discrete choice experiment survey. Participants were asked to choose a preferred treatment option in 9 choice questions. Each included a pair of hypothetical treatment profiles that have similar attributes/outcomes with varying levels. Outcomes included prostate biopsy outcome and treatment-related risks of erectile dysfunction (ED) and urinary incontinence (UI). We calculated the maximum risk of side effect patients were willing to tolerate in exchange for increased benefit. Preferences were further explored via clinical and demographic data. RESULTS: About 223 subjects with a mean age of 64.8 years completed the survey. Respondents were willing to accept a 1.51%-point increase in new ED risk for a 1%-point increase in favorable biopsy outcome. They were also willing to accept a 0.93%-point increase in new UI risk for a 1%-point increase in biopsy outcome. Subjects who perceived their cancer to be more aggressive had higher risk tolerance for UI. Younger men were willing to tolerate less ED risk than older men. Respondents with greater than college level of education had a lower risk tolerance for ED or UI. CONCLUSIONS: Results may inform development and regulatory evaluation for future HIFU ablation devices by providing supplemental information from the patient perspective.

Preferences for potential benefits and risks for gene therapy in the treatment of sickle cell disease.

Objective of this study is to quantify benefit-risk tradeoffs pertaining to potential gene therapies among adults and parents/caregivers of children with sickle cell disease (SCD). A discrete-choice experiment survey was developed in which respondents selected their preferred treatment alternatives in a series of experimentally controlled pairs of hypothetical gene therapies and a "no gene therapy" option. Gene therapy alternatives were defined based on the chance of eliminating SCD symptoms, expected increases in life expectancy they could offer, treatment-related risk of death, and potential increases in lifetime cancer risk. Respondents made selections based on their current disease severity and in the context of expectations of worsened disease. Three clinical sites and 1 patient organization recruited 174 adult patients and 109 parents of children with SCD to complete the survey. Adult and parent respondents were generally willing to choose gene therapies, but the adults required higher expected levels of efficacy (ie, higher chance of eliminating symptoms) than parents to choose gene therapies that conferred mortality risks of ≥10%. When adults and parents of children with less severe symptoms were asked to consider scenarios of higher levels of disease severity, the increased risk tolerance, and the lowest acceptable level of efficacy for gene therapies with mortality risks dropped by >50%. Baseline SCD symptoms are a major driver of gene therapy acceptability. Adults and parents of patients with milder symptoms may prefer other treatment options; however, an expectation of symptoms deterioration triggers strong reassessment of the acceptable benefit-risk balance of this novel technology.

Progressively Unsupervised Generative Attentional Networks with Adaptive Layer-Instance Normalization for Image-to-Image Translation.

Unsupervised image-to-image translation has received considerable attention due to the recent remarkable advancements in generative adversarial networks (GANs). In image-to-image translation, state-of-the-art methods use unpaired image data to learn mappings between the source and target domains. However, despite their promising results, existing approaches often fail in challenging conditions, particularly when images have various target instances and a translation task involves significant transitions in shape and visual artifacts when translating low-level information rather than high-level semantics. To tackle the problem, we propose a novel framework called Progressive Unsupervised Generative Attentional Networks with Adaptive Layer-Instance Normalization (PRO-U-GAT-IT) for the unsupervised image-to-image translation task. In contrast to existing attention-based models that fail to handle geometric transitions between the source and target domains, our model can translate images requiring extensive and holistic changes in shape. Experimental results show the superiority of the proposed approach compared to the existing state-of-the-art models on different datasets.

Adaptation of the WOMAC for Use in a Patient Preference Study.

OBJECTIVES: To adapt a patient-reported outcome (PRO) measure, the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), into efficacy attributes for a discrete choice experiment (DCE) survey designed to quantify the relative importance of endpoints commonly used in knee osteoarthritis (KOA) trials. METHODS: The adaptation comprised four steps: (1) selecting domains of interest; (2) determining presentation and framing of selected attributes; (3) determining attribute levels; and (4) developing choice tasks. This process involved input from multiple stakeholders, including regulators, health preference researchers, and patients. Pretesting was conducted to evaluate if patients comprehended the adapted survey attributes and could make trade-offs among them. RESULTS: The WOMAC pain and function domains were selected for adaption to two efficacy attributes. Two versions of the discrete choice experiment (DCE) instrument were created to compare efficacy using (1) total domain scores and (2) item scores for "walking on a flat surface." Both attributes were presented as improvement from baseline scores by levels of 0%, 30%, 50%, and 100%. Twenty-six participants were interviewed in a pretest of the instrument (average age 60 years; 58% female; 62% had KOA for ≥ 5 years). The participants found both versions of attributes meaningful and relevant for treatment decision-making. They demonstrated willingness and ability to tradeoff improvements in pain and function separately, though many perceived them as inter-related. CONCLUSIONS: This study adds to the growing literature regarding adapting PRO measures for patient preference studies. Such adaptation is important for designing a preference study that can incorporate a clinical trial's outcomes with PRO endpoints.

Upper limb manual training for children with cerebral palsy: A systematic review and network meta-analysis of randomized controlled trials.

OBJECTIVE: There are different upper limb manual training protocols, namely constraint-induced movement therapy, modified constraint-induced movement therapy, hand-arm bimanual intensive training, hand-arm bimanual intensive training including lower extremity, action observation training, and mirror therapy, available for improving functional outcomes in children with cerebral palsy. However, the effect and priority of these strategies remain unclear. DATA SOURCES: We searched the PubMed, Cochrane Library, and Embase databases for relevant articles from inception to October 12, 2022. REVIEW METHODS: To assess the effect and priority of different strategies of upper limb manual training protocols through a systematic review and network meta-analysis of randomized controlled trials. RESULTS: We included 22 randomized controlled trials in this network meta-analysis. The ranking probability and standard mean differences with 95% credible intervals of the comparison between placebo and other forms of upper limb manual training were as follows: mirror therapy = 2.83 (1.78, 3.88), hand-arm bimanual intensive training including the lower extremity = 0.53 (0.09, 0.96), constraint-induced movement therapy = 0.44 (0.18, 0.71), hand-arm bimanual intensive training = 0.41 (0.15, 0.67), modified constraint-induced movement therapy = 0.39 (0.03, 0.74), and action observation training = 0.18 ( - 0.29, 0.65). No significant inconsistency was noted between the results of direct and indirect comparisons. CONCLUSION: We suggest that mirror therapy could be the upper limb manual training protocol of choice for improving functional outcomes in patients with cerebral palsy.

A Versatile and Scalable Platform That Streamlines Data Collection for Patient-Centered Studies: Usability and Feasibility Study.

BACKGROUND: The Food and Drug Administration Center for Biologics Evaluation and Research (CBER) established the Biologics Effectiveness and Safety (BEST) Initiative with several objectives, including the expansion and enhancement of CBER's access to fit-for-purpose data sources, analytics, tools, and infrastructures to improve the understanding of patient experiences with conditions related to CBER-regulated products. Owing to existing challenges in data collection, especially for rare disease research, CBER recognized the need for a comprehensive platform where study coordinators can engage with study participants and design and deploy studies while patients or caregivers could enroll, consent, and securely participate as well. OBJECTIVE: This study aimed to increase awareness and describe the design, development, and novelty of the Survey of Health and Patient Experience (SHAPE) platform, its functionality and application, quality improvement efforts, open-source availability, and plans for enhancement. METHODS: SHAPE is hosted in a Google Cloud environment and comprises 3 parts: the administrator application, participant app, and application programming interface. The administrator can build a study comprising a set of questionnaires and self-report entries through the app. Once the study is deployed, the participant can access the app, consent to the study, and complete its components. To build SHAPE to be scalable and flexible, we leveraged the open-source software development kit, Ionic Framework. This enabled the building and deploying of apps across platforms, including iOS, Android, and progressive web applications, from a single codebase by using standardized web technologies. SHAPE has been integrated with a leading Health Level 7 (HL7®) Fast Healthcare Interoperability Resources (FHIR®) application programming interface platform, 1upHealth, which allows participants to consent to 1-time data pull of their electronic health records. We used an agile-based process that engaged multiple stakeholders in SHAPE's design and development. RESULTS: SHAPE allows study coordinators to plan, develop, and deploy questionnaires to obtain important end points directly from patients or caregivers. Electronic health record integration enables access to patient health records, which can validate and enhance the accuracy of data-capture methods. The administrator can then download the study data into HL7® FHIR®-formatted JSON files. In this paper, we illustrate how study coordinators can use SHAPE to design patient-centered studies. We demonstrate its broad applicability through a hypothetical type 1 diabetes cohort study and an ongoing pilot study on metachromatic leukodystrophy to implement best practices for designing a regulatory-grade natural history study for rare diseases. CONCLUSIONS: SHAPE is an intuitive and comprehensive data-collection tool for a variety of clinical studies. Further customization of this versatile and scalable platform allows for multiple use cases. SHAPE can capture patient perspectives and clinical data, thereby providing regulators, clinicians, researchers, and patient advocacy organizations with data to inform drug development and improve patient outcomes.

Relationship Between Weight Status and Self-Image Mediated by Pubertal Timing and Athletic Competence: A Cohort Study With Taiwanese Adolescents.

Background: Self-image reflects overall self-acceptance in developing adolescents. Using a representative cohort of Taiwanese youth, this study aims to explore the relationship between weight status, pubertal timing, athletic competence, and adolescent self-image. Methods: Data come from the Taiwan Youth Project that comprised a longitudinal cohort of adolescents (N = 2690, 51% males, Mage = 13.3 ± 0.5 years) surveyed annually from seventh grade. Self-image was measured by perceived satisfaction with appearance and physique. Weight status was proxied by self-reported body mass index (BMI; kg/m2). Pubertal timing was defined using the Pubertal Developmental Scale, which mainly measured physical changes in puberty. Athletic competence was assessed by experiences with participation in competitive sports and self-perceived talent for sports. Linear regression analysis was applied to test for an association between BMI and self-image. In order to test for mediating roles of pubertal timing and athletic competence, Hayes' PROCESS macro on SPSS was conducted applying 5,000 bootstrap resamples with 95% confidence intervals of the indirect effect. Results: BMI was inversely associated with self-image in both males (ß = -0.074, [-0.095, -0.053]) and females (ß = -0.095, [-0.122, -0.069]). The boot-strapped 95% confidence intervals indicated statistically significant mediating effects of pubertal timing (ß = -0.008, [-0.015, -0.001]) and athletic competence (ß = -0.006, [-0.011, -0.002]) in the link between BMI and self-image in females, whilst only athletic competence mediated this association (ß = -0.006, [-0.009, -0.002]) in males. Moreover, BMI at baseline were also associated with long-term self-image in males (ß = -0.037, [-0.057, -0.017]) and females (ß = 0.132, [0.073, 0.190]). Conclusions: Understanding the mediating factors may help enhance adolescents' self-image by providing guidance on healthy weight and physical activity behaviors according to different stages of pubertal progression.

Effectiveness of interferential current therapy in patients with knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials.

We conducted a systematic review and meta-analysis to assess the effectiveness of interferential current therapy (IFC) in patients with knee osteoarthritis. We searched PubMed, Cochrane Library, Embase, ClinicalKey, and Scopus for relevant studies from their date of launch to March 22, 2022. We included randomized controlled trials (RCTs) in which IFC was applied to knee osteoarthritis patients and the outcomes of pain scores or functional scales were assessed. Ten RCTs with 493 patients met the inclusion criteria. Nine RCTs were included in the meta-analysis. The IFC groups exhibited significant improvements relative to the control groups for short-term pain scores (SMD = - 0.64, 95% CI - 1.04 to - 0.25, P = 0.001), long-term pain scores (SMD = - 0.36, 95% CI - 0.60 to - 0.11, P = 0.005), and short-term Western Ontario and McMaster Universities Osteoarthritis Index scores (SMD = - 0.39, 95% CI - 0.77 to - 0.02, P = 0.04). All included studies did not observe any obvious adverse effects of IFC. IFC can be recommended as a treatment for knee osteoarthritis because it improves short- and long-term pain and short-term function. However, large-scale and high-quality RCTs with longer follow-up are required to establish an appropriate standardized treatment.

Effectiveness of mental simulation practices after total knee arthroplasty in patients with knee osteoarthritis: A systematic review and meta-analysis of randomized controlled trials.

Mental simulation practices, such as motor imagery, action observation, and guided imagery, have been an intervention of interest in neurological and musculoskeletal rehabilitation. Application of such practices to postoperative patients in orthopedics, particularly after total knee arthroplasty, has resulted in favorable physical function outcomes. In this systematic review and meta-analysis, we wish to determine the effectiveness of mental simulation practices with standard physical therapy compared to standard physical therapy alone in patients who underwent total knee arthroplasty in terms of postoperative pain, physical functions, and patient-reported outcome measures. We identified randomized controlled trials from inception to August 28, 2021, by using the PubMed, Cochrane Library, EMBASE, and Scopus databases. Data collection was completed on August 28, 2021. Finally, eight articles (249 patients) published between 2014 and 2020 were included. The meta-analysis revealed that mental simulation practices caused more favorable results in pain [standardized mean difference = -0.42, 95% confidence interval (CI) (-0.80 to -0.04), P = 0.03], range of motion [0.55, 95% CI (0.06-1.04), P = 0.03], maximal strength of quadriceps [1.21, 95% CI (0.31-2.12), P = 0.009], and 36-Item Short-Form Survey [0.53, 95% CI (0.14-0.92), P = 0.007]. Our data suggest that mental simulation practices may be considered adjunctive to standard physiotherapy after total knee arthroplasty in patients with knee osteoarthritis.

Examining the Relationship between Gender Contentedness and Sex-Related Experiences among Taiwanese Youth.

Little is known about how gender contentedness is related to sex-related experiences among Taiwanese adolescents. Secondary analysis of data (n = 2624, Mage = 13.3 ± 0.47 years and 51% males) on a longitudinal youth cohort was used to track the evolving development of sex-related experiences such as exposure to sexually explicit media, romantic experiences, and sexual behaviors. Hierarchical multinomial logistic regression analyses were applied to study the effects of gender contentedness on sex-related outcome variables. The results showed that nearly 10% of the subjects were not contented with their gender. As compared to peers, gender-discontented adolescents had a higher likelihood of exposures to sexually explicit media (odds ratio [OR]. = 1.70, 95% confidence interval [CI]. = 1.18-2.46) and risky sex behaviors (OR = 2.22, 95% CI = 1.03-4.81). These results shed light on the impact of self-perceived gender contentedness on sex-related experiences in Taiwanese adolescents. Our findings are helpful for the development of practical guidance on sexual health issues, particularly for those who are discontented with their gender.

Polytriphenylamine and Poly(styrene-co-hydroxystyrene) Blends as High-Performance Anticorrosion Coating for Iron.

An electroactive polytriphenylamine (PTPA-C6) is blended with poly(styrene-co-hydroxystyrene) (PS-co-PHS) as coating layers to enhance protection efficiency of PTPA-C6 on iron substrate in 3.5% sodium chloride (NaCl) solution. Experimental results show that incorporation of hydroxyl group to the polystyrene not only increases the miscibility of PTPA-C6 with PS through the hydrogen bond formation, but also enhances the bonding strength between the polymer coating layer and iron substrate. These improvements lead to superior enhancement in anticorrosion performance of PTPA-C6, even after thermal treatment. Protection efficiency (PE) of PTPA-C6 increases from 81.52% of the PTPA-C6 itself to over 94.40% under different conditions (PEmax = 99.19%).

Trajectory of Food Insecurity and Its Association with Longitudinal Mental Health and Sleep Outcomes in Adolescents from Economically Disadvantaged Families.

BACKGROUND: Adolescence is a critical transition period in the course of human development. Although food insecurity (FI) has been shown to be associated with adverse mental health and sleep outcomes in US adolescents, there is a paucity of research examining the relationships between FI, mental health, and sleep outcomes in Taiwanese adolescents. Furthermore, it is unknown how the change of FI over time (i.e., the trajectory of FI) is related to health outcomes. METHODS: The data come from the Taiwan Database of Children and Youth in Poverty, which is a national longitudinal project measuring FI in five survey waves (2009-2017). We employed group-based trajectory modeling to classify various FI trends over the five waves using STATA. Furthermore, a generalized estimating equation analysis was conducted with FI trajectories as the independent variable to see how FI trajectory is related to mental health and sleep outcomes. RESULTS: In total, 1921 participants aged 12-18 years in the first wave were deemed valid for the analysis. We classified the participants into four FI trajectory groups: persistently low FI (24.8%), persistently moderate FI (64.7%), declining from high to low FI (4.1%), and food-secure groups (6.4%). As compared to food-secure adolescents, the persistently moderate FI group was more likely to have mental problems (ß = 0.30, [95% confidence interval 0.21-0.38]), while the other FI groups were only marginally associated with mental health problems. Moreover, adolescents in the persistently low FI group (ß = 0.13, [0.02-0.23]) and persistently moderate FI group (ß = 0.39, [0.29-0.48]) were found to have more sleep problems than those in the food-secure group. CONCLUSIONS: Our study describes the FI profile of adolescents from economically disadvantaged families and the difficulties they might encounter. With this information, healthcare providers can aid adolescents in the early stages of mental health problems and provide guidance when appropriate.

The Effect of Religion on Psychological Resilience in Healthcare Workers During the Coronavirus Disease 2019 Pandemic.

Background: Healthcare workers in the front line of diagnosis, treatment, and care of patients with coronavirus disease 2019 (COVID-19) are at great risk of both infection and developing mental health symptoms. This study aimed to investigate the following: (1) whether healthcare workers in general hospitals experience higher mental distress than those in psychiatric hospitals; (2) the role played by religion and alexithymic trait in influencing the mental health condition and perceived level of happiness of healthcare workers amidst the stress of the COVID-19 pandemic; and (3) factors that influence the resilience of healthcare workers at 6 weeks' follow-up. Methods: Four-hundred and fifty-eight healthcare workers were recruited from general and psychiatric hospitals, and 419 were followed-up after 6 weeks. All participants filled out the 20-item Toronto Alexithymia Scale, five-item Brief-Symptom Rating Scale, and the Chinese Oxford Happiness Questionnaire. Results: Under the stress of the COVID-19 pandemic, 12.3% of frontline healthcare workers in general hospitals reported having mental distress and perceived lower social adaptation status compared with those working in psychiatric hospitals. Christians/Catholics perceived better psychological well-being, and Buddhists/Taoists were less likely to experience mental distress. The results at 6 weeks of follow-up showed that the perceived lower social adaptation status of general hospital healthcare workers was temporary and improved with time. Christian/Catholic religion and time had independent positive effects on psychological well-being; however, the interaction of Christian/Catholic religion and time had a negative effect. Conclusions: Collectivism and individualism in the cultural context are discussed with regard to alexithymic trait and Buddhist/Taoist and Christian/Catholic religious faiths. Early identification of mental distress and interventions should be implemented to ensure a healthy and robust clinical workforce for the treatment and control of the COVID-19 pandemic.

Formative Research for an Innovative Smartphone Application to Improve Distribution of Healthy Foods to Corner Stores in Baltimore City.

We sought to collect information about the operations of wholesalers and store owner perceptions of smartphones to plan for and create a smartphone application that will facilitate the distribution of healthy foods to corner stores. In-depth interviews were conducted with wholesalers, corner store owners, distributors, and food environment experts in Baltimore City, Maryland, which included providing feedback for a mockup of the app. Store owners that were comfortable with smartphones liked the idea of the app because it was economically practical, culturally suitable, simple and easy to use, and provided a large variety of items at a fair or low price. We found that barriers to uptake among corner store owners would be high delivery costs, no foreign language capability, and a complicated user interface. This work will inform future projects that will utilize mHealth technology to improve distribution of healthier foods in food deserts.

Prostate Ablation Using High Intensity Focused Ultrasound: A Literature Review of the Potential Role for Patient Preference Information.

PURPOSE: The FDA (Food and Drug Administration) recently allowed the marketing of 2 high intensity focused ultrasound devices for prostate tissue ablation indications after previous rejections for a prostate cancer indication due to insufficient data on clinical effectiveness or direct patient benefit. We reviewed the safety and effectiveness of high intensity focused ultrasound and knowledge regarding patient preferences, such as tolerance for adverse events associated with high intensity focused ultrasound ablation of tissue, in men with prostate cancer. This may inform decision making for device developers and the FDA. MATERIALS AND METHODS: We searched PubMed® and gray literature, including FDA reports for relevant data on 1) the safety and effectiveness of primary and salvage high intensity focused ultrasound of localized prostate cancer in studies performed in or outside the United States and 2) patient preference information on high intensity focused ultrasound related safety and effectiveness outcomes. RESULTS: We found no high intensity focused ultrasound effectiveness data relevant to clinical decision making, such as overall or prostate cancer specific survival, in the United States. Long-term effectiveness data from outside the United States were sparse and outcomes varied. We also found no patient preference data on high intensity focused ultrasound treatment in men with prostate cancer. CONCLUSIONS: The lack of long-term high intensity focused ultrasound oncological data in an American population has brought new challenges to prostate cancer stakeholders, including clinicians, patients and the FDA. Patient preference information from future patient studies on high intensity focused ultrasound could provide additional information to patients, clinicians, and current and prospective device developers. In addition, it can be used by regulators in benefit-risk evaluations of this class of treatment devices.

Ageing in India: Financial hardship from health expenditures.

India's rapidly ageing population raises concerns about the burden of health care payments among older individuals who may have both limited income and greater health care needs. Using a nationally representative household survey, we investigate the association between age and financial hardship due to health expenditures. We find that both the probability of experiencing health problems and mean total out-of-pocket health expenditures increase with age. Second, the probability of households experiencing catastrophic health expenditures increases with each additional member aged 60 and above-33% of households with one 60+ member and 38% of households with 2 or more 60+ members experienced catastrophic health expenditures, compared to only 20% in households with all members under the age of 60 years. Lastly, we show that individuals aged 60 and above had a much higher probability of becoming impoverished as a result of health expenditures-the probability of impoverishment for 60+ individuals was 3 percentage points higher than for individuals under the age of 60. Overall, around 4.8% of the older population, representing 4.1 million people, fell into poverty. The results suggest that there is an urgent need for public investments in financial protection programs for older people in India.

Applying stated-preference methods to improve health systems in sub-Saharan Africa: a systematic review.

INTRODUCTION: Sub-Saharan African health systems must balance shifting disease burdens with desires for robust institutions. Stated-preference methods have been applied extensively to elicit health care workers' preferences and priorities for rural practice. This systematic review characterizes the range of their applications to African health systems problems. Areas covered: A PRISMA protocol was submitted to PROSPERO. Six databases were queried for peer-reviewed articles using quantitative stated-preference methods to evaluate a health systems-related trade-off. Quality was assessed using the PREFS checklist. Seventy-seven articles published between 1996 and 2017 met review criteria. Methods were primarily choice-based: discrete-choice experiments (n = 46), ranking/allocation techniques (n = 21), conjoint analyses (n = 7), and best-worst scaling (n = 3). Trade-offs fell into six 'building blocks': service features (n = 27), workforce incentives (n = 17), product features (n = 14), system priorities (n = 14), insurance features (n = 4), and research priorities (n = 1). Five countries dominated: South Africa (n = 11), Ghana (n = 9), Malawi (n = 9), Uganda (n = 9), and Tanzania (n = 8). Discrete-choice experiments were of highest quality (mean score: 3.36/5). Expert commentary: Stated-preference methods have been applied to many health systems contexts throughout sub-Saharan Africa. Studies examined established strategic areas, especially primary health care for women, prevention and treatment of infectious diseases, and workforce development. Studies have neglected the emerging areas of non-communicable diseases.

Kuei-Lu-Er-Xian-Jiao extract enhances BMP-2 production in osteoblasts.

Osteoporosis is a common skeletal disorder, resulting from an imbalance in bone resorption relative to formation. Bone morphogenetic protein (BMP) is a key regulator in bone formation and osteoblastic differentiation. Hence, compounds that promote BMP expression may be suitable candidates for osteoporosis treatment. This study examined the effects of the traditional Chinese medicinal agent, Kuei-Lu-Er-Xian-Jiao (KLEXJ), on BMP-2 production in osteoblasts. We found that KLEXJ extract promoted osteoblastic differentiation marker ALP activity and increased BMP-2 production; pretreatment with PI3K and Akt inhibitors, or small interfering RNA (siRNA), reduced these effects. KLEXJ also enhanced PI3K and Akt phosphorylation. Treatment of osteoblastic cells with NF-κB inhibitors (TPCK or PDTC) markedly inhibited KLEXJ-enhancement of ALP activity and BMP-2 production. KLEXJ also significantly promoted p65 phosphorylation, while treatment with PI3K and Akt inhibitors antagonized KLEXJ-enhanced p65 phosphorylation. Thus, KLEXJ enhances ALP activity and BMP-2 production of osteoblasts through the PI3K/Akt/ NF-κB signaling pathway and hence may be suitable in the treatment of osteoporosis.

Parental bonding in males with adjustment disorder and hyperventilation syndrome.

BACKGROUND: The purpose of the study was to identify the style of parental bonding and the personality characteristics that might increase the risk of hyperventilation and adjustment disorder. METHODS: A total of 917 males were recruited, 156 with adjustment disorder and hyperventilation syndrome (AD + HY), 273 with adjustment disorder without hyperventilation syndrome (AD-HY), and 488 healthy controls. All participants completed the Parental Bonding Instrument, Eysenck Personality Questionnaire, and Chinese Health Questionnaire. RESULTS: Analysis using structural equation models identified a pathway relationship in which parental bonding affected personality characteristics, personality characteristics affected mental health condition, and mental health condition affected the development of hyperventilation or adjustment disorder. Males with AD-HY perceived less paternal care, and those with AD + HY perceived more maternal protection than those with adjustment disorder and those in the control group. Participants with AD-HY were more neurotic and less extroverted than those with AD + HY. Both groups showed poorer mental health than the controls. CONCLUSIONS: Although some patients with hyperventilation syndrome demonstrated symptoms of adjustment disorder, there were different predisposing factors between the two groups in terms of parental bonding and personality characteristics. This finding is important for the early intervention and prevention of hyperventilation and adjustment disorder.