Topiramate suppresses peri-infarct spreading depolarization and improves outcomes in a rat model of photothrombotic stroke.

Ischemic stroke can cause depolarized brain waves, termed peri-infarct depolarization (PID). Here, we evaluated whether topiramate, a neuroprotective drug used to treat epilepsy and alleviate migraine, has the potential to reduce PID. We employed a rat model of photothrombotic ischemia that can reliably and reproducibly induce PID and developed a combined electrocorticography-laser speckle contrast imaging (ECoG-LSCI) platform to monitor neuronal activity and cerebral blood flow (CBF) simultaneously. Topiramate administration after photothrombotic ischemia did not rescue CBF but significantly restored somatosensory evoked potentials in the forelimb area of the primary somatosensory cortex. Moreover, infarct volume was investigated by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and neuronal survival was evaluated by Nissl staining. Mechanistically, the levels of inflammatory markers, such as ED1 (CD68), Iba-1, and GFAP, decreased significantly after topiramate administration, as did BDNF expression, while the expression of NeuN and Bcl-2/Bax increased, which is indicative of reduced inflammation and improved neuroprotection.

Exploring the genetics of lithium response in bipolar disorders.

BACKGROUND: Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N = 2064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II. RESULTS: We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism. CONCLUSIONS: Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.

Insights into the molecular mechanism of ParABS system in chromosome partition by HpParA and HpParB.

The ParABS system, composed of ParA (an ATPase), ParB (a DNA binding protein), and parS (a centromere-like DNA), regulates bacterial chromosome partition. The ParB-parS partition complex interacts with the nucleoid-bound ParA to form the nucleoid-adaptor complex (NAC). In Helicobacter pylori, ParA and ParB homologs are encoded as HpSoj and HpSpo0J (HpParA and HpParB), respectively. We determined the crystal structures of the ATP hydrolysis deficient mutant, HpParAD41A, and the HpParAD41A-DNA complex. We assayed the CTPase activity of HpParB and identified two potential DNA binding modes of HpParB regulated by CTP, one is the specific DNA binding by the DNA binding domain and the other is the non-specific DNA binding through the C-terminal domain under the regulation of CTP. We observed an interaction between HpParAD41A and the N-terminus fragment of HpParB (residue 1-10, HpParBN10) and determined the crystal structure of the ternary complex, HpParAD41A-DNA-HpParBN10 complex which mimics the NAC formation. HpParBN10 binds near the HpParAD41A dimer interface and is clamped by flexible loops, L23 and L34, through a specific cation-π interaction between Arg9 of HpParBN10 and Phe52 of HpParAD41A. We propose a molecular mechanism model of the ParABS system providing insight into chromosome partition in bacteria.

Discovery of oral chemotherapeutic reversal agents for treating multidrug resistance cancer.

The major limitation of cancer treatment is multidrug resistance (MDR), which leads to the inactivation of chemotherapeutic drugs and greater than 90% mortality. To solve this ordeal, we applied ligand-based drug design and bioiosteric replacement strategy from an indazole to a pyrazole ring to discover compounds 27 and 43 with good potential for reversing drug resistance in combination with paclitaxel, and their reversal fold values were 53.2 and 51.0 at 5 µM, respectively, against an MDR cancer cell line (KBvin). Based on the PK profile results, we selected compound 43 with a longer half-life for mechanistic and animal experiments. Combination treatment with compound 43 and paclitaxel-induced apoptosis and enhanced subG1 by decreasing mitochondrial membrane potential in KBvin cells. In addition, 43 also inhibited P-gp function by interfering with ATPase activity. Meanwhile, cotreatment with compound 43 and paclitaxel significantly suppressed tumor growth (TGI = 55.5%) at a dose of 200 mg/kg (PO) in a xenograft model and showed no obvious liver or kidney toxicity by H&E staining. Overall, compound 43 may serve as a safe and effective oral resistance reversal chemotherapeutic agent.

Evaluation of cutout factors with small and narrow fields using various dosimetry detectors in electron beam keloid radiotherapy.

BACKGROUND: The inherent problems in the existence of electron equilibrium and steep dose fall-off pose difficulties for small- and narrow-field dosimetry. OBJECTIVE: To investigate the cutout factors for keloid electron radiotherapy using various dosimetry detectors for small and narrow fields. METHOD: The measurements were performed in a solid water phantom with nine different cutout shapes. Five dosimetry detectors were used in the study: pinpoint 3D ionization chamber, Farmer chamber, semiflex chamber, Classic Markus parallel plate chamber, and EBT3 film. RESULTS: The results demonstrated good agreement between the semiflex and pinpoint chambers. Furthermore, there was no difference between the Farmer and pinpoint chambers for large cutouts. For the EBT3 film, half of the cases had differences greater than 1%, and the maximum discrepancy compared with the reference chamber was greater than 2% for the narrow field. CONCLUSION: The parallel plate, semiflex chamber and EBT3 film are suitable dosimeters that are comparable with pinpoint 3D chambers in small and narrow electron fields. Notably, a semiflex chamber could be an alternative option to a pinpoint 3D chamber for cutout widths≥3 cm. It is very important to perform patient-specific cutout factor calibration with an appropriate dosimeter for keloid radiotherapy.

Prevalence, dimensions, and correlates of excessive daytime sleepiness in community-dwelling older adults: the Yilan study, Taiwan.

BACKGROUND: Daytime sleepiness is an important health problem. However, the dimensionality of the Epworth Sleepiness Scale (ESS) in older adults remains unclear. This study aimed to determine the prevalence of ESS-defined excessive daytime sleepiness in older adults. Furthermore, the dimensionality of ESS and its respective correlates were also compared. MATERIALS AND METHODS: This is a community-based survey in which community-dwelling older adults aged ≥ 65 years participated. Excessive daytime sleepiness was assessed using the ESS and was defined as an ESS score of > 10. Exploratory factor analysis was performed to identify the ESS factors. Multiple logistic regression analysis was used to examine the independent correlates of the ESS-defined and factor-specific correlates of excessive daytime sleepiness. RESULTS: In total, 3978 older adults participated in this study. The mean age was 76.6 ± 6.7 years, with 53.8% ≥ 75 years, and 57.1% were female. The prevalence of ESS-defined excessive daytime sleepiness was 16.0%. An exploratory factor analysis revealed two factors in the ESS, which were designated as 'passive' and 'active' according to the soporific levels of ESS items loaded in each factor. Multiple logistic regression showed that male, illiteracy, depression, disability, short sleep duration and no exposure to hypnotics were risk indicators for ESS-defined excessive daytime sleepiness. However, the correlates for passive and active factor-defined excessive daytime sleepiness differ in pattern, especially in variables related to education, exercise, mental health, and sleep. CONCLUSIONS: The prevalence of ESS-defined excessive daytime sleepiness is high, and its correlates vary among older adults. This study also suggests a dual ESS structure in community-dwelling older adults.

Daytime sleepiness is prevalent in older adults.The Epworth Sleepiness Scale (ESS) has dual constructs in older adults.Correlates for excessive daytime sleepiness vary by constructs of the ESS.

Associations among global long interspersed nuclear element-1 DNA methylation, metal exposure, and chronic kidney disease.

Long interspersed nuclear element-1 (LINE-1) methylation serves as an indicator of global DNA methylation. This study explored the correlation between LINE-1 methylation and chronic kidney disease (CKD). We also evaluated whether LINE-1 methylation could modify the association between CKD and metal exposure. A total of 213 patients with clinically defined CKD, without hemodialysis and 416 age and sex matched controls were recruited. Levels of LINE-1 methylation, total urinary arsenic, blood lead, blood cadmium, and plasma selenium were assessed. The results reveal a positive association between LINE-1 methylation and CKD, with an odds ratio (OR) of 5.30 (95% confidence interval: 2.81 to 9.99). Total urinary arsenic and blood cadmium concentrations were positively related with LINE-1 methylation. This study was the first to observe that low plasma selenium, high blood cadmium, and high blood lead levels significantly and additively interact with increased LINE-1 methylation to increase the OR of CKD. Additionally, high LINE-1 methylation interacted multiplicatively with low plasma selenium to increase the OR of CKD (p < 0.001). This study highlighted the significant association between LINE-1 hypermethylation and CKD. Furthermore, the results demonstrate that LINE-1 methylation can interact with high blood cadmium or low plasma selenium to affect CKD risk.

Enhancing the sequence coverage of nanodiamond-extracted early secretory proteins from the Mycobacterium tuberculosis complex.

The unambiguous identification of protein species requires high sequence coverage. In this study, we successfully improved the sequence coverage of early secretory 10 kDa cell filtrate protein (CFP-10) and 6 kDa early secretory antigenic target (ESAT-6) proteins from the Mycobacterium tuberculosis complex (MTC) in broth culture media with the use of the 4-chloro-α-cyanocinnamic acid (Cl-CCA) matrix. Conventional matrices, α-cyano-hydroxy-cinnamic acid (CHCA) and 2,5-dihydroxybenzoic acid (DHB), were also used for comparison. After nanodiamond (ND) extraction, the sequence coverage of the CFP-10 protein was 87% when CHCA and DHB matrices were used, and the ESAT-6 protein was not detected. On the other hand, the sequence coverage for ND-extracted CFP-10 and ESAT-6 could reach 94% and 100%, respectively, when the Cl-CCA matrix was used and with the removal of interference from bovine serum albumin (BSA) protein and α-crystallin (ACR) protein. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) was also adopted to analyze the protein mass spectra. A total of 6 prominent ion signals were observed, including ESAT-6 protein peaks at mass-to-charge ratios (m/z) of ∼7931, ∼7974, ∼9768, and ∼9813 and CFP-10 protein peaks at m/z of ∼10 100 and ∼10 660. The ESAT-6 ion signals were always detected concurrently with CFP-10 ion signals, but CFP-10 ion signals could be detected alone without the ESAT-6 ion signals. Furthermore, the newly found ESAT-6 peaks were also confirmed using a Mag-Beads-Protein G kit with an ESAT-6 antibody to capture the ESAT-6 protein, which was also consistent with the sequence coverage analysis.

Sex difference in the association between excessive daytime sleepiness and health-related quality of life in community-dwelling older adults: The Yilan study, Taiwan.

OBJECTIVES: The association between excessive daytime sleepiness and health-related quality of life among older adults and at-risk individuals remains unclear. This study examined relationships between excessive daytime sleepiness and unfavorable health-related quality of life and explored the moderating effect of sex. STUDY DESIGN: This was a community-based study of adults aged 65 years or more. Excessive daytime sleepiness was defined as a score exceeding 10 on the Epworth Sleepiness Scale. Multiple logistic regression analyses were used to examine the relationships between excessive daytime sleepiness and health-related quality of life. The moderating effect of sex was examined by testing interaction terms. MAIN OUTCOME MEASURES: Health-related quality of life was measured using the Short Form 12 Health Survey, which includes a physical component summary and a mental component summary. Unfavorable health-related quality of life was defined as the lowest tertile of the scores for both components. RESULTS: In total, 3788 individuals participated. After controlling for covariates, older adults with excessive daytime sleepiness did not have an unfavorable physical component summary but were more likely to have an unfavorable mental component summary (odds ratio 1.96; 95 % confidence interval 1.47-2.61). When stratified by sex, excessive daytime sleepiness was associated with a poor physical component summary in men (odds ratio 1.77, 95 % confidence interval 1.00-3.13) but not in women. CONCLUSIONS: Excessive daytime sleepiness was associated with a poor mental component summary in both sexes; however, the association with a poor physical component summary was specific to men.

Lithium response in bipolar disorder is associated with focal adhesion and PI3K-Akt networks: a multi-omics replication study.

Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.

Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference.

Most genome-wide association studies (GWAS) of major depression (MD) have been conducted in samples of European ancestry. Here we report a multi-ancestry GWAS of MD, adding data from 21 cohorts with 88,316 MD cases and 902,757 controls to previously reported data. This analysis used a range of measures to define MD and included samples of African (36% of effective sample size), East Asian (26%) and South Asian (6%) ancestry and Hispanic/Latin American participants (32%). The multi-ancestry GWAS identified 53 significantly associated novel loci. For loci from GWAS in European ancestry samples, fewer than expected were transferable to other ancestry groups. Fine mapping benefited from additional sample diversity. A transcriptome-wide association study identified 205 significantly associated novel genes. These findings suggest that, for MD, increasing ancestral and global diversity in genetic studies may be particularly important to ensure discovery of core genes and inform about transferability of findings.

Alternation of social behaviors for zebrafish (Danio rerio) in response to acute cold stress.

Low temperature is one of the most common abiotic stresses for aquatic ectotherms. Ambient low temperatures reduce the metabolic rate of teleosts, therefore, teleosts have developed strategies to modulate their physiological status for energy saving in response to cold stress, including behaviors, circulatory system, respiratory function, and metabolic adjustments. Many teleosts are social animals and they can live in large schools to serve a variety of functions, including predator avoidance, foraging efficiency, and reproduction. However, the impacts of acute cold stress on social behaviors of fish remain unclear. In the present study, we test the hypothesis that zebrafish alter their social behaviors for energy saving as a strategy in response to acute cold stress. We found that acute cold stress increased shoaling behavior that reflected a save-energy strategy for fish to forage and escape from the predators under cold stress. The aggressive levels measured by fighting behavior tests and mirror fighting tests were reduced by cold treatment. In addition, we also found that acute cold stress impaired the learning ability but did not affect memory. Our findings provided evidence that acute cold stress alters the social behaviors of aquatic ectotherms for energy saving; knowledge of their responses to cold is essential for their conservation and management.

A predictive survival model for patients with stage IV oropharyngeal squamous cell carcinoma treated with chemoradiation.

PURPOSE: To evaluate the pre-treatment and post-treatment clinical factors associated with rate of survival at 1, 3, and 5 years in stage IV oropharyngeal cancer patients treated with concurrent chemoradiation with/without neoadjuvant chemotherapy. METHODS: This retrospective cohort study involved 128 Stage IV oropharyngeal cancer patients that were treated at our tertiary referral center between 2008 and 2020. The pre-treatment and post-treatment clinical parameters including nutritional status and inflammatory markers were retrospectively reviewed. RESULTS: The 5-year overall survival rate for all patients was 36.72%. The disease-specific survival (DSS) at 1-year and 3-year were 80% and 63%, whereas the disease-free survival (DFS) at 1-year and 3-year were 49% and 40%, respectively. In multivariate analyses, pretreatment hemoglobin (Hb) < 12 g/dL (hazard ratio [HR] 2.551, 95% confidence interval [CI] 1.366-4.762, p = 0.003), pretreatment systemic immune inflammation (SII) ≥ 1751 (HR 2.173, 95% CI 1.015-4.652, p = 0.046), and posttreatment systemic inflammation response index (SIRI) ≥ 261 (HR 2.074, 95% CI 1.045-4.115, p = 0.037) were independent indicators for worsened DSS. Pretreatment Hb < 12 g/dl (HR 1.692, 95% CI 1.019-2.809, p = 0.032), pretreatment SII ≥ 1751 (HR 1.968, 95% CI 1.061-3.650, p = 0.032), and posttreatment SII ≥ 1690 (HR 1.922, 95% CI 1.105-3.345, p = 0.021) were independent indicators for worsened DFS. A nomogram was developed using pretreatment Hb, pretreatment SII, and posttreatment SIRI to forecast DSS. CONCLUSIONS: The pretreatment Hb, pretreatment SII, posttreatment SII, and posttreatment SIRI are associated with survival in patients with stage IV oropharyngeal cancers. The developed nomogram aids in survival prediction and treatment adjustment.

Different dimensions of daytime sleepiness predicted mortality in older adults: Sex and muscle power-specific risk in Yilan Study, Taiwan.

OBJECTIVES: This study aimed to investigate the relationship between daytime sleepiness and mortality risk among older adults. The moderating effects of sex and physical function were examined. METHODS: This 9-year follow-up study was conducted with community-dwelling individuals aged ≥65 years. Daytime sleepiness was evaluated using the Epworth Sleepiness Scale (ESS). Exploratory factor analysis (EFA) was used to examine the ESS factors. Handgrip strength was measured to assess physical function, and the highest quartile was defined as good muscle power. Cox regression analysis was used to estimate the 9-year all-cause mortality risk. The interaction terms were examined to evaluate their moderating effect. RESULTS: In total, 2588 individuals participated in the study. The EFA explored two factors: the passive factor (PF) and the active factor (AF). After controlling for various covariates, the cutoff-defined daytime sleepiness (ESS≥11), total raw scores, and factor scores of the ESS all failed to predict mortality risk. The 3-way interaction terms showed statistical significance in terms of [sex × PF × muscle power (p = 0.03)] but not for [sex × AF × muscle power (p = 0.11)]. Specifically, PF predicted mortality risk in women with good muscle power (hazard ratio (HR): 1.48; 95 % confidence interval (CI): 1.04-2.10), which is female-specific. In contrast, AF predicted mortality risk only in men with good muscle power (HR: 1.35; 95 % CI: 1.02-1.78). CONCLUSIONS: The ESS-measured daytime sleepiness in older adults is multidimensional. The mortality risk for each dimension was determined based on sex and physical function.

The differential pattern of associations between nighttime sleep disturbances with dimensions of daytime sleepiness in community-dwelling older adults, the Yilan study, Taiwan.

BACKGROUND: The association between nighttime sleep disturbance and daytime sleepiness remains unclear. This study aimed to examine the relationships between various domains of nighttime sleep disturbance, daytime sleepiness, and their specific dimensions. METHODS: This was a community-based cross-sectional study. The participants were adults aged 65 years and older from Yilan City, Taiwan. Daytime sleepiness (DS) was defined using the Epworth Sleepiness Scale (ESS) with scores ≥ 11. The ESS dimensions were further examined using exploratory factor analysis. The highest 15% factor scores for each factor were defined as factor-specific DS. Various domains of nighttime sleep disturbance were assessed using the Pittsburgh Sleep Quality Index. Logistic regression analysis was used to examine the independent relationships among various nighttime sleep disturbances, ESS, and its dimensions. RESULTS: Of the 2585 participants, a total of 59.0% were women. Two factors were identified by exploratory factor analysis and were designated as 'passive factor' and 'active factor'. Multiple logistic regression analyses elucidated that short sleep duration was a common risk indicator for ESS-defined (odds ratio (OR): 2.01; 95% confidence interval (CI): 1.43-2.83), passive factor-defined (OR: 2.23, 95% CI: 1.65-3.00), and active factor-defined DS (OR: 1.47, 95% CI: 1.07-2.00). Hypnotic use was associated with a lower risk of both ESS-defined (OR: 0.66, 95% CI: 0.47-0.92) and passive factor-defined DS (OR:0.69, 95% CI: 0.52-0.92). Bathroom use (OR: 1.41, 95% CI: 1.04-1.91), coughing or snoring (OR: 2.14, 95% CI: 1.01-4.56), and sleep efficiency (OR: 0.42; 95% CI: 0.31-0.57) were uniquely associated with active factor-defined DS. CONCLUSION: Two factors were identified in the ESS, revealing factor-specific correlates of DS. Specifically, ESS- and passive factor-defined DS shared similar correlates. In contrast, some correlates seem unique to active-factor-defined DS.

Perivascular adipose tissue and adipocyte-derived exosomal miRNAs maintain vascular homeostasis.

Perivascular adipose tissue (PVAT), a fat layer that provides structural support to the blood vessels, is a cushion protecting the vessel wall from neighbouring tissues during contraction and relaxation. PVAT actively regulates vascular tone by secreting vasoactive (vasodilatory and vasoconstrictive) factors (e.g., adipokines, batokines, and lipokines) or microRNA (miRNA)-containing exosomes to reduce the hyperreactivity induced by obesity. Of particular interest are adipocyte-derived exosomal miRNAs, which act as crucial regulators, counteracting the detrimental effects of obesity on cardiovascular well-being. These exosomes serve as potent messengers, facilitating the transport of miRNAs and other bioactive molecules involved in intercellular communication. Undoubtedly, the unique function of exosomal miRNAs promotes vascular homeostasis by fine-tuning endothelial function, vascular remodelling, and inflammatory environment, thereby preventing cardiovascular disease. The collective findings comprehensively explain their protective functions by exploring the intricate mechanisms through which PVAT and adipocyte-derived exosomal miRNAs collaboratively orchestrate vascular health. Taken together, this review strategically focuses on PVAT, exosomes, and adipocyte-derived miRNAs, offering valuable insights that can potentially inform the development of targeted interventions for cardiovascular diseases.

Exploring the genetics of lithium response in bipolar disorders.

Background: Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N=2,064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II. Results: We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism. Conclusions: Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.

Factors Associated With Levels of Public Engagement in Protective Behaviors During the Early COVID-19 Pandemic: Causal-Comparative Study Based on the Health Belief Model.

BACKGROUND: While the challenges of COVID-19 are still unfolding, the enhancement of protective behavior remains a top priority in global health care. However, current behavior-promoting strategies may be inefficient without first identifying the individuals with lower engagement in protective behavior and the associating factors. OBJECTIVE: This study aimed to identify individuals with and potential contributing factors to low engagement in protective behavior during the COVID-19 pandemic. METHODS: This is a causal-comparative study. A theory-based web-based survey was used to investigate individuals' protective behavior and potential associating factors. During June 2020, the distribution of the survey was targeted to 3 areas: Taiwan, Japan, and North America. Based on the theory of the health belief model (HBM), the survey collected participants' various perceptions toward COVID-19 and a collection of protective behaviors. In addition to the descriptive analysis, cluster analysis, ANOVA, and Fisher exact and chi-square tests were used. RESULTS: A total of 384 responses were analyzed. More than half of the respondents lived in Taiwan, followed by Japan, then North America. The respondents were grouped into 3 clusters according to their engagement level in all protective behaviors. These 3 clusters were significantly different from each other in terms of the participants' sex, residency, perceived barriers, self-efficacy, and cues of action. CONCLUSIONS: This study used an HBM-based questionnaire to assess protective behaviors against COVID-19 and the associated factors across multiple countries. The findings indicate significant differences in various HBM concepts among individuals with varying levels of behavioral engagement.

Impact of Varying Chest Wall Target Volume Delineation on Postmastectomy Radiation Therapy Outcomes in Breast Cancer Patients with Implant-Based Reconstruction.

BACKGROUND: The target volume for post-mastectomy radiation therapy (PMRT) in breast cancer patients with reconstruction has been a subject of debate. Traditionally, the RT chest wall (CW) volume encompasses the entire implant. For patients with retropectoral implants, the deep lymphatic plexus dorsal part of the implant is no longer considered high risk and can be omitted. This study aimed to assess the radiation dose distribution and treatment outcomes associated with different CW delineation according to ESTRO ACROP guideline for patients who have undergone implant-based reconstruction. METHODS: We conducted a retrospective review of breast cancer patients who underwent a mastectomy followed by two-stage implant-based breast reconstruction and adjuvant radiation therapy (RT) between 2007 and 2022. The expanders/implants were positioned retropectorally. The chest wall target volumes were categorized into two groups: the prepectoral group, which excluded the deep lymphatic plexus, and the whole expander group. RESULTS: The study included 26 patients, with 15 in the prepectoral group and 11 in the whole expander group. No significant differences were observed in normal organ exposure between the two groups. There was a trend toward a lower ipsilateral lung mean dose in the prepectoral group (10.2 vs. 11.1 Gy, p = 0.06). Both groups exhibited limited instances of reconstruction failure and local recurrence. CONCLUSIONS: For patients undergoing two-stage expander/implant retropectoral breast reconstruction and PMRT, our data provided comparable outcomes and normal organ exposure for those omitting the deep lymphatic plexus.