Dilute polyelectrolyte solutions: recent progress and open questions.

Polyelectrolytes are a class of polymers possessing ionic groups on their repeating units. Since counterions can dissociate from the polymer backbone, polyelectrolyte chains are strongly influenced by electrostatic interactions. As a result, the physical properties of polyelectrolyte solutions are significantly different from those of electrically neutral polymers. The aim of this article is to highlight key results and some outstanding questions in the polyelectrolyte research from recent literature. We focus on the influence of electrostatics on conformational and hydrodynamic properties of polyelectrolyte chains. A compilation of experimental results from the literature reveals significant disparities with theoretical predictions. We also discuss a new class of polyelectrolytes called poly(ionic liquid)s that exhibit unique physical properties in comparison to ordinary polyelectrolytes. We conclude this review by listing some key research challenges in order to fully understand the conformation and dynamics of polyelectrolytes in solutions.

Fluorescent Solvatochromic Probes for Long-Term Imaging of Lipid Order in Living Cells.

High-resolution spatio-temporal monitoring of the cell membrane lipid order provides visual insights into the complex and sophisticated systems that control cellular physiological functions. Solvatochromic fluorescent probes are highly promising noninvasive visualization tools for identifying the ordering of the microenvironment of plasma membrane microdomains. However, conventional probes, although capable of structural analysis, lack the necessary long-term photostability required for live imaging at the cellular level. Here, an ultra-high-light-resistant solvatochromic fluorescence probe, 2-N,N-diethylamino-7-(4-methoxycarbonylphenyl)-9,9-dimethylfluorene (FπCM) is reported, which enables live lipid order imaging of cell division. This probe and its derivatives exhibit sufficient fluorescence wavelengths, brightness, polarity responsiveness, low phototoxicity, and remarkable photostability under physiological conditions compared to conventional solvatochromic probes. Therefore, these probes have the potential to overcome the limitations of fluorescence microscopy, particularly those associated with photobleaching. FπCM probes can serve as valuable tools for elucidating mechanisms of cellular processes at the bio-membrane level.

Unique E2-binding specificity of artificial RING fingers in cancer cells.

Ubiquitin (Ub)-conjugating enzymes (E2s) are involved in various pathways for Ub transfer and deubiquitinating activities. These enzymes are associated with cancers such as breast cancer which is the second deadliest type of malignancy among women. Here, we revealed the unique E2-binding property and the auto-ubiquitination of artificial RING fingers (ARFs). Circular dichroism spectra showed the characteristic structures of ARFs. The proline, lysine, leucine, threonine and cysteine (PKLTC) sequence of ARF was important for E2-recognition and its mutations induced obvious changes in the E2-binding specificity and the auto-ubiquitination activity of ARF. The ARF mutants were applicable to detection of most of E2 activities. Furthermore, adding the ARF mutant C35A to cancer cells promoted its auto-ubiquitination, leading to the preferential detection of E2 UbcH5b activity. The present work opens up a new avenue for investigating intracellular E2 activities for the fatal diseases.

Sporadic gastric juvenile polyposis with a novel SMAD4 nonsense mutation in a mosaic pattern.

A 50-year-old female was diagnosed with gastric hyperplastic polyps 7 years before and was followed up at another hospital. She was referred to our hospital because of the growth of gastric polyps and progression of anemia. She had no family history of polyposis. The polyps were observed only in the stomach, increased in size and number, and the erythematous edema got worse. Endoscopic mucosal resection (EMR) of the gastric polyp was performed. Pathologically, the gastric polyp was hamartomatous polyp, and the intervening mucosa between polyps showed no atypical structure without inflammation. Given that gastric juvenile polyposis (GJP) was clinically suspected, a genetic test using peripheral blood was performed. Target resequencing and Sanger sequencing analysis revealed a nonsense mutation in the SMAD4 gene at codon 169. The mutation was detected at a low frequency of 11%, and considered a mosaic mutation. Therefore, she was diagnosed with a sporadic GJP, and total gastrectomy was performed. Immunostaining of SMAD4 for the resected specimen showed a mixture of stained and unstained area in the epithelium of the polyp, indicating partial loss of SMAD4 expression. To our knowledge, this is the first reported case of GJP with a nonsense SMAD4 mutation at codon 169 in a mosaic pattern.

The Effect of Japanese Herbal Medicines (Kampo) Goreisan and Saireito on the Prevention of Recurrent Chronic Subdural Hematoma: A Prospective Randomized Study.

BACKGROUND AND OBJECTIVES: Chronic subdural hematoma (CSDH) sometimes recurs after surgical treatment and requires reoperation. In Japan, Japanese herbal medicines (Kampo), such as Goreisan and Saireito, have been used as adjunctive therapies to prevent the recurrence of CSDH. However, no prospective randomized study has proven the efficacy of Kampo medicine in all patients. To investigate whether Goreisan and Saireito reduce the postoperative recurrence of CSDH in a prospective randomized study. METHODS: Between April 2017 and July 2019, a total of 118 patients who underwent initial burr hole surgery for CSDH were randomly assigned to the following 3 groups: (1) Goreisan for 3 months (Group G), (2) Saireito for 3 months (Group S), and (3) no medication (Group N). The primary end point was symptomatic recurrence within 3 months postoperatively, and the secondary end point was complications associated with the administration of Kampo medicine. RESULTS: Among 118 patients, 114 (Group N, n = 39; Group G, n = 37; and Group S, n = 38) were included in our analysis. In this study, byakujutsu (containing Atractylodes rhizome ) Goreisan and Saireito were used, unlike other prospective randomized studies in which sojutsu (containing Atractylodes lancea rhizome) Goreisan was used. The overall recurrence rate was 11.4% (13/114: 10 for Group N, 2 for Group G, and 1 for Group S). The recurrence rate of Group G was significantly lower than that of Group N (5.4% vs 25.6%; P = .043). The recurrence rate of Group S was also significantly lower than that of Group N (2.6% vs 25.6%; P = .02). No patients developed complications associated with the administration of Kampo medicine. CONCLUSION: This is the first study to show that Kampo medicine reduced the recurrence rate of CSDH in an overall population. This study demonstrated that byakujutsu Goreisan and Saireito may have favorable effects, unlike other studies, because byakujutsu has stronger anti-inflammatory activity than sojutsu.

Social Support and Associated Factors Among Men and Women in Pre-COVID Substance Use Treatment.

Low levels of social support are related to negative health outcomes, representing further obstacles to recovery from substance use disorder (SUD). This study examined relationships among stressors, symptoms and social support in 124 women and 102 men engaged in two outpatient public sector substance use treatment programs. Multiple linear regression analyses were utilized to assess relationships between variables of interest and social support. Men reported significantly lower social support than women. Food insecurity was associated with lower social support for men (ß= -13.6 [95% CI -26.7, -0.4], p = 0.04). When examining emotional support and tangible aid, victimization history was related to lower support (both types) for women while food insecurity was associated with lower support (both types) for men. Depression was related to lower emotional support among both men and women. Substance use treatment programs should explicitly target social support and related stressors to facilitate recovery for the individuals they serve.

Structural and Dynamic Changes of Nucleosome upon GATA3 Binding.

Pioneer factors, which can directly bind to nucleosomes, have been considered to change chromatin conformations. However, the binding impact on the nucleosome is little known. Here, we show how the pioneer factor GATA3 binds to nucleosomal DNA and affects the conformation and dynamics of nucleosomes by using a combination of SAXS, molecular modeling, and molecular dynamics simulations. Our structural models, consistent with the SAXS data, indicate that only one of the two DNA binding domains, N- and C-fingers, of GATA3 binds to an end of the DNA in solution. Our MD simulations further showed that the other unbound end of the DNA increases the fluctuation and enhances the DNA dissociation from the histone core when the N-finger binds to a DNA end, a site near the entry or exit of the nucleosome. However, this was not true for the binding of the C-finger that binds to a location about 15 base pairs distant from the DNA end. In this case, DNA dissociation occurred on the bound end. Taken together, we suggest that the N-finger and C-finger bindings of GATA3 commonly enhance DNA dissociation at one of the two DNA ends (the bound end for the C-finger binding and the unbound end for the N-finger binding), leading to triggering a conformational change in the chromatin.

Artificial RING finger reveals unique auto-ubiquitination with E2 specificity.

Ubiquitin (Ub)-conjugating enzymes (E2s) transfer activated Ub from Ub-activating enzymes (E1s) to substrates and are associated with various cancers and neurological disorders. In this study, the unique properties of E2-binding and auto-ubiquitination of artificial RING fingers (ARFs) were demonstrated in ubiquitination assays. Circular dichroism spectra indicated the characteristic structures of ARFs. Point mutations of 31 PKLTC35 in ARF by tryptophan (Trp) resulted in dramatic changes in E2 specificity and the type of Ub chain elongation of mono- and polyubiquitination. The Trp residue was a cue that changed the ubiquitination activity of ARF via E2-binding. Furthermore, the ARF mutants interacted with all 11 E2s and then promoted auto-ubiquitination. Thus, the use of the ARF mutants allowed specific detection of E2 activities during ubiquitination. The present study opens up a new avenue for researching E2 activities related to the fatal diseases.

Evaluating Technologies to Identify Fentanyl and Adulterants in Street Drug Paraphernalia: Qualitative Perspectives of Service Providers and Their Clientele.

Background: Opioid overdose deaths continue to present major public health challenges in the U.S. Harm reduction agencies have begun using drug checking technologies to identify adulterants in the local drug supply and reduce overdose risk among people who use drugs (PWUD). Through qualitative and ethnographic methods, we assess the use of portable mass spectrometers at a harm reduction agency in a Northeastern U.S. city. Methods: We conducted participant observation, and on-the-spot qualitative interviews with harm-reduction staff members (n = 10) and their clientele (n = 17) between May 2019 and December 2020. Interviews explored emic views on drug checking (process, logistics, technology), and perceived benefits and challenges. We used thematic content analysis techniques to code and analyze interview transcriptions. Results: Implementation and use of drug checking devices were not free of challenges and malfunctions, often delaying drug checking opportunities and increasing suspicions and distrust among clients. Yet, staff members perceived that when working properly, or in conjunction with an additional device, they offered information about purchased drugs that could empower clients and potentially lead to positive behavior change. Use of these devices also enhanced engagement between harm reduction staff and PWUD, facilitating meaningful conversations around self-advocacy and harm reduction engagement. Conclusion: We report qualitative findings on the experiences and perceptions of drug checking devices among harm reduction staff and PWUD. Our findings indicate that use of this technology has the potential to decrease risk behaviors, expand health promotion services, and help reduce high rates of fentanyl-related overdose.

Temperature-independent lasing wavelength of highly stacked InAs quantum dot laser fabricated on InP(311)B substrate with Bi irradiation.

In this study, the effects of bismuth (Bi) irradiation on InAs quantum dot (QD) lasers operating in the telecommunication wavelength band were investigated. Highly stacked InAs QDs were grown on an InP(311)B substrate under Bi irradiation, and a broad-area laser was fabricated. In the lasing operation, the threshold currents were almost the same, regardless of Bi irradiation at room temperature. These QD lasers were operated at temperatures between 20 and 75°C, indicating the possibility of high-temperature operation. In addition, the temperature dependence of the oscillation wavelength changed from 0.531 nm/K to 0.168 nm/K using Bi in the temperature range 20-75°C.

Usefulness of Early Genetic Diagnosis for Twins With a Family History of Congenital Nephrotic Syndrome.

We reported a dichorionic diamniotic placental twin (DD twin) with a family history of a congenital nephrotic syndrome of the Finnish type (CNF), of which the parent had heterozygous for the NPHS1 gene mutation. The DD twin was born at 36 weeks gestation, and their fused placenta weighed 1,340 g. Although the first-born child had heavy proteinuria and hypoalbuminemia and needed daily albumin replacement to manage severe edema, the second had only mild proteinuria after birth. Genetic testing performed 28 days after birth detected homozygous for the NPHS1 gene mutation in only the first-born child but not in the second, which resulted in performing invasive left nephrectomy and peritoneal dialysis (PD) to manage edema in the first. For DD twins with a family history of CNF, prenatal diagnosis of CNF may be difficult. Therefore, close postnatal clinical observation and early genetic testing are essential for the diagnosis of CNF.

Cervical radiculopathy due to extracranial vertebral artery dissection treated by stent placement with a flow diversion effect: illustrative case.

BACKGROUND: Cervical radiculopathy due to extracranial vertebral artery dissection (VAD) is extremely rare. The disease is usually treated with conservative treatment because of its favorable prognosis. However, there is a possibility that conservative treatment may bring about no improvement in radiculopathy. Although stent placement with a flow diversion effect may be effective in such cases, there are no reported cases that were treated with stent placement. OBSERVATIONS: A 40-year-old healthy man presented with severe right neck pain, right arm pain, and right arm weakness after cracking his neck. A neurological examination revealed right C5 radiculopathy. Neuroimaging studies revealed right extracranial VAD. The VAD compressed the right C5 nerve root. Although medications were administered, there was no improvement in the symptoms. He experienced severe radicular pain. The authors performed stent placement with a flow diversion effect 10 days after the onset of VAD. His radicular pain improved immediately after the procedure, and the remaining radiculopathy completely improved within 1 month. Follow-up angiography showed complete improvement of the VAD. LESSONS: Stent placement with a flow diversion effect may be considered when radiculopathy that hinders a patient's daily life exists. Stent placement may bring about rapid improvement in radiculopathy, especially radicular pain.

Entry Site Is Associated With Aortic Enlargement After Pre-emptive Endovascular Repair for Uncomplicated Type B Aortic Dissection.

OBJECTIVES: We aimed to examine the mid-term results corresponding to the entry site in patients who underwent pre-emptive thoracic endovascular aortic aneurysm repair (TEVAR) for uncomplicated type B aortic dissection (TBAD). METHODS: We included 27 patients who underwent pre-emptive TEVAR for uncomplicated TBAD between September 2014 and December 2019. We divided the patients into 2 groups depending on the proximal landing zone (zone 2 group, zone ≥3 group) and retrospectively analyzed the risk of all-cause and aorta-related mortality, aortic events (rupture, open conversion, and secondary intervention), and aortic enlargement (≥5 mm). RESULTS: The median age of the patients was 53 (47-65) years. The median duration from the onset of uncomplicated TBAD to TEVAR was 43 (30-99) days, and the median follow-up duration was 48 (36-57) months. The maximum preoperative diameter of the dissected aorta was 40 mm in the zone 2 group and 35 mm in the zone ≥3 group (p=0.134). There was no case of hospital death or spinal cord ischemia; however, there was 1 (3.7%) case of perioperative stroke in the zone 2 group. Multivariate analysis of the risk factors for aortic enlargement following pre-emptive TEVAR for uncomplicated TBAD revealed that only zone 2 landing was an independent risk factor. The estimated Kaplan-Meier curve showed a higher rate of aortic enlargement in the zone 2 group at 4 years after pre-emptive TEVAR (46.4% vs 0%, log-rank test; p=0.011). CONCLUSIONS: In this study on TBAD, we found that zone 2 landing was associated with aortic enlargement after pre-emptive TEVAR. In cases where the distance from the left subclavian artery to a major entry point was short, there were more cases of aortic dilatation. CLINICAL IMPACT: The effectiveness of entry closure for type B aortic dissection was demonstrated in the INSTEAD XL trial. The cause of aortic enlargement after pre-emptive endovascular treatment for type B aortic dissection remains controversial. In the present study, zone 2 landing was a risk factor for aortic enlargement after pre-emptive thoracic endovascular aortic aneurysm repair (TEVAR) for uncomplicated type B dissection. Patients with zone 2 landing should be closely followed up after pre-emptive TEVAR.

Mortality and morbidity of extremely low birth weight infants in Japan, 2015.

BACKGROUND: In Japan, the mortality rate of extremely low birth weight (ELBW) infants is notably low in comparison with other developed countries, but the prevalence of chronic lung disease (CLD) and retinopathy of prematurity (ROP) is relatively high. This study aimed to estimate the mortality and morbidity of ELBW infants born in 2015 who were admitted to neonatal intensive care units (NICUs) in Japan and to examine the factors that affected the short-term outcomes of these infants. We also compared the mortality of ELBW infants born in 2005, 2010, and 2015. METHODS: We analyzed the mortality, morbidity, and factors related to short-term outcomes of ELBW infants, using data from 2782 infants born in 2015 and registered at NICUs in Japan. RESULTS: The mortality rates during NICU stays were 17.0%, 12.0%, and 9.8% for ELBW infants born in 2005, 2010, and 2015, respectively. Among ELBW infants born in 2015, multiple logistic regression analysis showed that short gestational age and low birthweight Z-score contributed to the increased risk of death. Births by cesarean section and antenatal corticosteroid administration were significantly associated with a reduced risk of death. Among infants who survived, CLD was observed in 53.1% and ROP requiring treatment was observed in 30.4%. CONCLUSIONS: Mortality in ELBW infants decreased significantly from 2005 to 2015. As CLD and ROP may affect quality of life and long-term outcomes of infants who survived, prevention strategies and management for these complications are critical issues in neonatal care in Japan.

Impact of depressed state on attention and language processing during news broadcasts: EEG analysis and machine learning approach.

While information enriches daily life, it can also sometimes have a negative impact, depending on an individual's mental state. We recorded electroencephalogram (EEG) signals from depressed and non-depressed individuals classified based on the Beck Depression Inventory-II score while they listened to news to clarify differences in their attention to affective information and the impact of attentional bias on language processing. Results showed that depressed individuals are characterized by delayed attention to positive news and require a more increased load on language processing. The feasibility of detecting a depressed state using these EEG characteristics was evaluated by classifying individuals as depressed and non-depressed individuals. The area under the curve in the models trained by the EEG features used was 0.73. This result shows that individuals' mental states may be assessed based on EEG measured during daily activities like listening to news.

A rapid and simple spectroscopic method for the determination of yeast cell viability using methylene blue.

Determination of cell viability is important in various microbiological studies. The microscopic method, counting dead cells stained by methylene blue (MB), has often been used for the determination of viability, although it is not efficient for the measurement of a large number of samples. Alternatively, some spectroscopic methods have been proposed to avoid tedious cell counting. One of these proposed methods detects the decrease in MB absorbance in the supernatant of cell suspension, because dead cells incorporate MB more efficiently than viable cells. However, at present, this spectroscopic method is rarely used due to its low throughput. Therefore, we devised a small-scale, rapid and simple method by improving several points as follows. (1) The peak wavelength of MB absorbance, 665 nm, was used to detect MB efficiently at the microtube scale. (2) The composition of the MB solution was improved by adding trisodium citrate. (3) The reaction time was shortened. And (4) the concentration ranges of both MB and cells, with which absorbance is linearly related to cell viability, were determined. The improved method enabled us to evaluate the dose-dependent toxicities of alcohols, antifungal/antimalarial quinacrine, and UV-C irradiation. The results were compatible with those of conventional microscopic counting and colony formation. The method would be applicable to automated determination and to various organisms such as bacteria and filamentous fungi which are difficult to be counted microscopically.

Jail-based reentry programming to support continued treatment with medications for opioid use disorder: Qualitative perspectives and experiences among jail staff in Massachusetts.

BACKGROUND: Individuals with opioid use disorder released to communities after incarceration experience an elevated risk for overdose death. Massachusetts is the first state to mandate county jails to deliver all FDA approved medications for opioid use disorder (MOUD). The present study considered perspectives around coordination of post-release care among jail staff engaged in MOUD programs focused on coordination of care to the community. METHODS: Focus groups and semi-structured interviews were conducted with 61 jail staff involved in implementation of MOUD programs. Interview guide development, and coding and analysis of qualitative data were guided by the Exploration, Preparation, Implementation, and Sustainment (EPIS) framework. Deductive and inductive approaches were used for coding and themes were organized using the EPIS. RESULTS: Salient themes in the inner context focused on the elements of reentry planning that influence coordination of post-release care including timing of initiation, staff knowledge about availability of MOUD in community settings, and internal collaborations. Findings on bridging factors highlighted the importance of interagency communication to follow pre-scheduled release dates and use of bridge scripts to minimize the gap in treatment during the transition. Use of navigators was an additional factor that influenced MOUD initiation and engagement in community settings. Outer context findings indicated partnerships with community providers and timely reinstatement of health insurance coverage as critical factors that influence coordination of post-release care. CONCLUSIONS: Coordination of MOUD post-release continuity of care requires training supporting staff in reentry planning as well as resources to enhance internal collaborations and bridging partnerships between in-jail MOUD programs and community MOUD providers. In addition, efforts to reduce systemic barriers related to unanticipated timing of release and reinstatement of health insurance coverage are needed to optimize seamless post-release care.

Escaping from the Cutoff Paradox by Accumulating Long-Chain Alcohols in the Cell Membrane.

The mechanism for the cutoff, an activity cliff at which long-chain alcohols lose their biological effects, has not been elucidated. Highly hydrophobic oleyl alcohol (C18:1) exists as a mixture of monomers and aggregated droplets in water. C18:1 did not inhibit the yeast growth but inhibited the growth of the slime mold without a cell wall. C18:1 exhibited toxicity to the yeast protoplast, which was enhanced by polyethylene glycol, a fusogen. Therefore, direct interactions of C18:1 with the membrane are crucial for the toxicity. The cutoff alcohols, C14 and C16, also exhibited strong toxicity obeying the Meyer-Overton correlation, in intact yeast cells whose membrane growth was suppressed in water. Taken together, the cutoff is avoidable by securing sufficient accumulation of the wall-permeable monomers in the membrane, which supports the lipid theory. It would be important to distinguish the effective drug structure localizing in the membrane and deal with the amount in the membrane.

A case of posterior cerebral artery occlusion that developed into an artery of Percheron infarction.

The thalamus is predominantly supplied by multiple small vessels originating from the posterior communicating artery and the P1 and P2 segments of the posterior cerebral artery (PCA). The artery of Percheron (AOP) is a rare anatomical variant of arterial supply to the thalamus. This single thalamic perforating branch supplies the bilateral thalamus so that occlusion results in a characteristic cerebral infarction. Herein, we report a case of posterior cerebral artery occlusion that developed into an AOP infarction. A 74-year-old man, who had undergone coronary artery bypass grafting 5 days previously presented with sudden consciousness disorder and tetraplegia, and was admitted to our hospital. Magnetic resonance imaging (MRI) revealed a hyper-intense area in the bilateral paramedian thalamus on diffusion-weighted imaging and a deficit of the left PCA on MR angiography (MRA). The patient was diagnosed with cardiogenic cerebral embolism, and immediately underwent mechanical thrombectomy (MT), thereby complete recanalization was obtained. Post-procedural MRI showed no new lesions, and the left PCA could keep patency. His consciousness disorder and tetraplegia improved; however, cognitive impairment and vertical gaze palsy persisted as sequelae. To the best of our knowledge, such cases have not been previously reported. Additionally, in this case, we were able to identify an AOP on digital subtraction angiography, which was considered to be the responsible artery.