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Arrestins bind active phosphorylated G protein-coupled receptors (GPCRs). Among the four mammalian subtypes, only arrestin-3 facilitates the activation of JNK3 in cells. In available structures, Lys-295 in the lariat loop of arrestin-3 and its homologue Lys-294 in arrestin-2 directly interact with the activator-attached phosphates. We compared the roles of arrestin-3 conformational equilibrium and Lys-295 in GPCR binding and JNK3 activation. Several mutants with enhanced ability to bind GPCRs showed much lower activity towards JNK3, whereas a mutant that does not bind GPCRs was more active. The subcellular distribution of mutants did not correlate with GPCR recruitment or JNK3 activation. Charge neutralization and reversal mutations of Lys-295 differentially affected receptor binding on different backgrounds but had virtually no effect on JNK3 activation. Thus, GPCR binding and arrestin-3-assisted JNK3 activation have distinct structural requirements, suggesting that facilitation of JNK3 activation is the function of arrestin-3 that is not bound to a GPCR.

Arrestin-1, or visual arrestin, exhibits an exquisite selectivity for light-activated phosphorylated rhodopsin (P-Rh*) over its other functional forms. That selectivity is believed to be mediated by two well-established structural elements in the arrestin-1 molecule, the activation sensor detecting the active conformation of rhodopsin and the phosphorylation sensor responsive to the rhodopsin phosphorylation, which only active phosphorylated rhodopsin can engage simultaneously. However, in the crystal structure of the arrestin-1–rhodopsin complex there are arrestin-1 residues located close to rhodopsin, which do not belong to either sensor. Here we tested by site-directed mutagenesis the functional role of these residues in wild type arrestin-1 using a direct binding assay to P-Rh* and light-activated unphosphorylated rhodopsin (Rh*). We found that many mutations either enhanced the binding only to Rh* or increased the binding to Rh* much more than to P-Rh*. The data suggest that the native residues in these positions act as binding suppressors, specifically inhibiting the arrestin-1 binding to Rh* and thereby increasing arrestin-1 selectivity for P-Rh*. This calls for the modification of a widely accepted model of the arrestin–receptor interactions.

The problem of filling bone cavities remains relevant in maxillofacial and oral surgery. There is a large selection of osteotropic materials, of various natures, for filling bone defects of different etiologies. The aim of our research was to improve the outcome of surgical treatment in a patient with a complicated mandibular fracture, with the use of a collagenic xenograft during osteosynthesis. In this article, we share our experience of the treatment of a patient with a complicated mandibular angle fracture, in combination with a follicular cyst. The obligate steps of treatment included stabilization of the bone fragments, decreasing the risk of fracture line malposition, using titan mini-plates, and shortening the time of bone regeneration, by filling the bone defect with osteotropic material. This approach allowed us to reduce the rehabilitation period and further prosthetic treatment after 4–5 months, without additional bone grafting manipulations. Thus, the use of collagen osteotropic materials, possessing osteoconductive properties, can improve the treatment of patients with mandibular fractures.

Se describe el caso de una mujer que consultó por dolor pélvico. Tenía una ecografía transvaginal que reportaba teratomas bilaterales de ovario. Fue llevada a cirugía laparoscópica durante la cual se extirparon 7 teratomas y 1 quiste folicular simple del ovario derecho y se realizó salpingooforectomía izquierda, encontrando 6 teratomas intraováricos. Los objetivos de esta publicación son reportar un caso atípico de múltiples lesiones ováricas sincrónicas y discutir algunos aspectos controversiales del manejo de los teratomas por laparoscopia.

Se describe el caso de una mujer que consultó por dolor pélvico. Tenía una ecografía transvaginal que reportaba teratomas bilaterales de ovario. Fue llevada a cirugía laparoscópica durante la cual se extirparon 7 teratomas y 1 quiste folicular simple del ovario derecho y se realizó salpingooforectomía izquierda, encontrando 6 teratomas intraováricos. Los objetivos de esta publicación son reportar un caso atípico de múltiples lesiones ováricas sincrónicas y discutir algunos aspectos controversiales del manejo de los teratomas por laparoscopia.This paper describes the case of a woman who complained of pelvic pain. She underwent a transvaginal ultrasound which revealed the presence of bilateral ovarian teratomas. She then underwent a laparoscopy in which 7 teratomas and one simple cyst were found and resected from the right ovary; 6 additional teratomas were found within the ovary following left-hand side salpingoophorectomy. This case is reported to increase the body of literature concerning multiple ovarian lesions and because no other reports about such a large amount of multiple teratomas which have been handled by laparoscopy despite the size and the number of the tumors could be found after conducting extensive research.

Rodrigo Duterte, known for his strongman reputation as the former mayor of Davao City, sparked the emergence of the Diehard Duterte Supporters (DDS) movement during his 2016 presidential campaign. Their frustration with the status quo, systemic inequality, and ongoing corruption fueled them to gain hope and security through Duterte's lens. However, Duterte's unfulfilled campaign promises disappointed many, leading to a surge of DDS who resisted his leadership. A descriptive phenomenological approach was utilized to explore the lived experiences of the six (6) former Duterte supporters through a semi-structured interview with fifteen (15) open-ended questions. The data was analyzed through Moustakas' phenomenological data analysis method. Results indicated that the participants' ideal leader and view of Duterte's presidency showed why they stopped supporting him. They expressed disappointment for themselves and Duterte. Moreover, they have gotten out of the cognitive dissonance chamber and resisted justifying the system. Results highlighted the essence of critical thinking, which allowed the former supporters to eliminate their cognitive dissonance and make smarter decisions. The study's central findings indicate that understanding the causes of growing unquestioning support for a political figure can better equip individuals to deal with it. [ABSTRACT FROM AUTHOR]

Background WHO documents characterize stunting as, '...impaired growth and development that children experience from poor nutrition, repeated infection, and inadequate psychosocial stimulation.' The equation of stunting with malnutrition is common. This contrasts with historic and modern observations indicating that growth in height is largely independent of the extent and nature of the diet. Subjects We measured 1716 Indonesian children, aged 6.0-13.2 years, from urban Kupang/West-Timor and rural Soe/West-Timor, urban Ubud/Bali, and rural Marbau/North Sumatra. We clinically assessed signs of malnutrition and skin infections. Results There was no relevant correlation between nutritional status (indicated by skinfold thickness) and height SDS (hSDS). In total 53% of boys, and 46% girls in rural Soe were stunted, with no meaningful association between mean of triceps and subscapular skinfolds (xÌSF) and height. Skinfold thickness was close to German values. Shortest and tallest children did not differ relevantly in skinfold thickness. The same applied for the association between hSDS and mid-upper-arm circumference (MUAC) using linear mixed effects models with both fixed and random effects. In total 35.6% boys and 29.2% girls in urban Ubud were overweight; 21.4% boys and 12.4% girls obese, but with mean hSDS = -0.3, still short. Relevant associations between hSDS and xÌSF and MUAC were only found among the overweight urban children confirming that growth is accelerated in overweight and obese children. There were no visible clinical signs of malnutrition or chronic infection in the stunted children. Conclusion The present data seriously question the concept of stunting as prima facie evidence of malnutrition and chronic infection., Author(s): C. Scheffler [sup.1] , M. Hermanussen [sup.2] , B. Bogin [sup.3] , D. S. Liana [sup.4] , F. Taolin [sup.5] , P. M. V. P. Cempaka [sup.5] , M. [...]

BackgroundThe Personal Responsibility and Work Opportunity Reconciliation Act (PRWORA) of 1996 gave states the option to withdraw Medicaid coverage of nonemergency care from most legal immigrants. Our goal was to assess the effect of PRWORA on hospital uncompensated care in the United States.MethodsWe collected the following state-level data for the period from 1994 through 1999: foreign-born, noncitizen population and health uninsurance rates (US Census Current Population Survey); percentage of teaching hospitals (American Hospital Association Annual Survey of Hospitals); and each state's decision whether to implement the PRWORA Medicaid bar for legal permanent residents or to continue offering nonemergency Medicaid coverage using state-only funds (Urban Institute). We modeled uncompensated care expenditures by state (also from the Annual Survey of Hospitals) in both univariate and multivariable regression analyses.ResultsWhen measured at the state level, there was no significant relationship between uncompensated care expenditures and states' percentage of noncitizen immigrants. Uninsurance rates were the only significant factor in predicting uncompensated hospital care expenditures by state.ConclusionsReducing the number of uninsured patients would most surely reduce hospital expenditures for uncompensated care. However, data limitations hampered our efforts to obtain a monetary estimate of hospitals' financial losses due specifically to the immigrant eligibility changes in PRWORA. Quantifying the impact of these provisions on hospitals will require better data sources.

This research aims to analyze the implementation of the inclusive Early Childhood Education curriculum model at Bright Kiddie Kindergarten Ponorogo, Indonesia. This research used a qualitative approach with a case study method. The informants for this research were the school principal, class teacher and teacher accompanying children with special needs. Data collection techniques used were interviews, observation, and documentation. Next, data analysis used interactive model analysis, and for the validity of the research data, the triangulation method was used. The research results showed that Bright Kiddie Kindergarten had children with special needs with different characteristics, needs and abilities. In implementing inclusive learning, the school used regular and pull-out class models with duplication, simplification, substitution and omission curriculum models according to the needs of each student with special needs. Children with special needs study with other children in regular classes. However, at certain times, they will be moved to another room to receive additional learning from special accompanying teachers. The curriculum model was also adjusted based on the identification and assessment results of each child with special needs as a basis for appropriate learning planning. Some duplicate the same curriculum as normal children (duplication), some simplify it without eliminating the substance (simplification), some replace it with equivalent material (substitution), and there are those who change it completely to suit the needs of each child.

Arrestin-1, or visual arrestin, exhibits an exquisite selectivity for light-activated phosphorylated rhodopsin (P-Rh*) over its other functional forms. That selectivity is believed to be mediated by two well-established structural elements in the arrestin-1 molecule, the activation sensor detecting the active conformation of rhodopsin and the phosphorylation sensor responsive to the rhodopsin phosphorylation, which only active phosphorylated rhodopsin can engage simultaneously. However, in the crystal structure of the arrestin-1–rhodopsin complex there are arrestin-1 residues located close to rhodopsin, which do not belong to either sensor. Here we tested by site-directed mutagenesis the functional role of these residues in wild type arrestin-1 using a direct binding assay to P-Rh* and light-activated unphosphorylated rhodopsin (Rh*). We found that many mutations either enhanced the binding only to Rh* or increased the binding to Rh* much more than to P-Rh*. The data suggest that the native residues in these positions act as binding suppressors, specifically inhibiting the arrestin-1 binding to Rh* and thereby increasing arrestin-1 selectivity for P-Rh*. This calls for the modification of a widely accepted model of the arrestin–receptor interactions. [ABSTRACT FROM AUTHOR]

O documento "RT-2030", elaborado pela Sociedade Brasileira de Radioterapia, delineia um plano estratégico para o desenvolvimento da radioterapia no Brasil ao longo da próxima década. Esta resenha oferece uma análise crítica das principais diretrizes e metas propostas pelo plano, abordando tópicos de importância para o setor, bem como seus impactos esperados na prática clínica, na inovação tecnológica e na formação profissional na área, além de discutir a viabilidade e os desafios associados à execução das estratégias delineadas no plano, oferecendo uma visão crítica sobre as suas implicações para o avanço da radioterapia no Brasil.

Meu propósito neste artigo é o de refletir sobre a relevância da relação intersubjetiva que se estabelece entre pesquisador/a e colaboradores/as na cena da entrevista de pesquisa. Meus argumentos estarão ancorados na Análise de Narrativa, mas se identificam com qualquer outra perspectiva construcionista de pesquisa e performativa de linguagem. Ao longo do artigo, apresento diferentes posições teóricas sobre as entrevistas de pesquisa e explico por que uma dimensão situada deveria ser considerada na pesquisa social qualitativa como um todo. Me servirei de uma lente goffmaniana para analisar dados oriundos de diferentes pesquisas narrativas realizadas por mim e por meus orientandos no sistema prisional do Rio de Janeiro. Em todas as análises, procuro mostrar como as respostas de entrevistados/as são contextualmente relativas e não podem ser alienadas da sequência interacional em que foram produzidas.

Background. The training methods for female athletes’ special physical training are considered to be a crucial aspect of the overall preparation system for competitive activity, which requires correct planning and implementation. Objectives. The study aimed to determine the impact of special preparatory exercises on female athletes engaged in Cossack Fight, depending on the characteristics of the body’s functioning in different phases of a specific biological cycle. Materials and methods. The study involved 20 female athletes aged 17-24 years who participated in Cossack Fight, and were divided into experimental and control groups. The qualification levels of female athletes in the experimental group were as follows: 1 – Master of Sports of Ukraine; 2 – Candidates for Master of Sports of Ukraine; 7 – 1 sports category. The control group comprised: 1 – Master of Sports of Ukraine; 2 – Candidates for Master of Sports of Ukraine; 7 – 1 sports category. The training program lasted for ten weeks and took place at a special preparatory and control-preparatory stage of the preparatory period. Results. The findings showed that the variability of training loads, depending on the phase of the ovarian-menstrual cycle, had a statistically significantly greater impact on the indicators of special physical fitness in the female athletes’ experimental group compared to the control group. Thus, after ten weeks of special physical training, the experimental group demonstrated a significant increase in the number of direct punches on the punching bag in 4 seconds (t=4.07; p

ABSTRACT Neisserial adhesin A (NadA) is a meningococcal surface protein included as recombinant antigen in 4CMenB, a protein-based vaccine able to induce protective immune responses against Neisseria meningitidis serogroup B (MenB). Although NadA is involved in the adhesion/invasion of epithelial cells and human myeloid cells, its function in meningococcal physiology is still poorly understood. To clarify the role played by NadA in the host-pathogen interaction, we sought to identify its cellular receptors. We screened a protein microarray encompassing 2,846 human and 297 mouse surface/secreted recombinant proteins using recombinant NadA as probe. Efficient NadA binding was revealed on the paired sialic acid-binding immunoglobulin-type lectins receptors 5 and 14 (Siglec-5 and Siglec-14), but not on Siglec-9 therein used as control. The interaction was confirmed by biochemical tools with the determination of the KD value in the order of nanomolar and the identification of the NadA binding site by hydrogen-deuterium exchange coupled to mass spectrometry. The N-terminal domain of the Siglec-5 that recognizes the sialic acid was identified as the NadA binding domain. Intriguingly, exogenously added recombinant soluble Siglecs, including Siglec-9, were found to decorate N. meningitidis surface in a NadA-dependent manner. However, Siglec-5 and Siglec-14 transiently expressed in CHO-K1 cells endorsed NadA binding and increased N. meningitidis adhesion/invasion while Siglec-9 did not. Taken together, Siglec-5 and Siglec-14 satisfy all features of NadA receptors suggesting a possible role of NadA in the acute meningococcal infection.IMPORTANCEBacteria have developed several strategies for cell colonization and immune evasion. Knowledge of the host and pathogen factors involved in these mechanisms is crucial to build efficacious countermoves. Neisserial adhesin A (NadA) is a meningococcal surface protein included in the anti-meningococcus B vaccine 4CMenB, which mediates adhesion to and invasion of epithelial cells. Although NadA has been shown to bind to other cell types, like myeloid and endothelial cells, it still remains orphan of a defined host receptor. We have identified two strong NadA interactors, Siglec-5 and Siglec-14, which are mainly expressed on myeloid cells. This showcases that NadA is an additional and key player among the Neisseria meningitidis factors targeting immune cells. We thus provide novel insights on the strategies exploited by N. meningitidis during the infection process, which can progress to a severe illness and death.

Background The global prevalence of type 2 diabetes mellitus (T2DM) in adolescents and young adults is dramatically increasing. The aim of this study was to explore numerous risk factors for the occurrence of Pre-DM or T2DM in subjects aged ≤40 years. Methods A cross-sectional study was conducted involving 100 subjects (50 subjects in the Pre-DM/T2DM group and 50 subjects in the Non Pre-DM/T2DM group). Main inclusion criteria: age ≤40 years, registered in our Diabetes and Endocrine Clinic. Data extracted included demographic, lifestyle, anthropometric, psychosocial, and family history data. Statistical analysis by binary logistic regression model. Results were considered significant at p

Measuring the disclosure of social activities carried out by Islamic banks is very important. However, the results of measuring the disclosure of social activities of Islamic banks in Indonesia still need to be higher when measured by the current CSR disclosure measurement index. The CSR disclosure measurement index often used in related research comes from research results in various countries in the Middle East and Southeast Asia. This is one of the considerations that causes the level of CSR disclosure of Islamic banks in Indonesia to be relatively low. Studies on developing an index for measuring CSR disclosure of Islamic banks in Indonesia are based on Sharia enterprise theory (SET). Based on the results of literacy studies of related research conducted in the Middle East, Southeast Asia, and Indonesia, several assessment dimension criteria need to be developed, including those related to the obligation of Islamic banks to report their social activities from the start of their establishment, environmental awareness education for employees, use of environmentally friendly materials. to support operational activities and collaboration with social communities in order to achieve acceleration and equal distribution of community welfare.

Series of time-resolved still images of the explosion dynamics of micrometer-sized water droplets after femtosecond laser-pulse irradiation were obtained for different laser-pulse intensities. Amplified pulses centered around a wavelength of 805 nm with 1-mJ energy and 60-fs duration were focused onto the droplet to initiate the dynamics. Several effects, such as forward and backward plumes, jets, water films, and shock waves, were investigated. Additionally, the influence of different pulse durations produced by chirping the laser pulses was observed. OCIS codes: 320.0320, 190.3970, 320.7120.

Este artigo discute a administração de conflitos e o acesso à justiça nas periferias paulistas a partir do caso de um condomínio situado em Guarulhos, na Região Metropolitana de São Paulo. Construído pelo Programa Minha Casa Minha Vida, foi um dos territórios estudados em duas edições da pesquisa da Universidade Federal de São Paulo (Unifesp) sobre os impactos da pandemia de covid-19 nas periferias paulistas, realizadas em 2020 e 2022. A metodologia utilizada nas duas edições da pesquisa envolveu entrevistas com moradores, observação participante e a elaboração de diários de campo discutidos pela equipe em reuniões periódicas, além do emprego de instrumentos quantitativos. Durante o trabalho de campo, a administração de conflitos entre os moradores do conjunto habitacional tornou-se um tema em evidência, especialmente devido a mudanças observadas na atuação da síndica entre 2020 e 2022 e à localização da “biqueira”, que passou a funcionar em um local mais visível em 2022. A presença incontornável da “biqueira” e os conflitos de vizinhança e familiares formaram um emaranhado de tensões latentes que atravessaram o cotidiano dos moradores e, vez ou outra, eclodiram em ameaças verbais e violência física. Contudo, não encontramos mecanismos de administração de conflito mais duradouros, fossem eles de autocomposição, fossem do PCC, fossem estatais, à exceção de incursões pontuais da polícia, da Justiça do Trabalho e da prisão, que compõe simbolicamente o dia a dia dos moradores, pois são, em boa medida, familiares, vizinhos ou conhecidos de pessoas presas.

Context: Hypercoagulopathy is a COVID-19 extra-pulmonary manifestation has drawn the attention of the scientists due to its risk of thromboembolism. Enoxaparin is an anticoagulant used to prevent hypercoagulopathy. Many factors have been associated with enoxaparin effectiveness. Aims: To analyze factors affecting enoxaparin effectiveness on coagulation, inflammation, and clinical outcomes. Methods: This retrospective cohort study involved hospitalized adult patients with COVID-19 from November 2020 to April 2021. Patients’ age, gender, body mass index (BMI), comorbidity, and laboratory results were extracted from medical records. Factors influencing enoxaparin efficacy on coagulation, inflammation, and clinical outcomes were analyzed using path analysis with SmartPLS 3.0 software. D-dimer and platelet values was determined as coagulation outcomes and C-reactive protein (CRP) value as an inflammation outcome. Clinical outcomes comprised of mortality, ventilator usage, and length of stay. Results: A total of 269 patients fulfilled the inclusion criteria. Most of the subjects were male (58%), 66% had comorbidities, 48.3% were aged ≥60 years old, and 65.8% had a BMI ≥ 25 kg/m2. Path analysis showed that age, BMI, and comorbidity affected disease severity (p0.05). Conclusions: Dosage is the main factor influencing enoxaparin efficacy on coagulation, inflammation, and clinical outcomes. The dosage is strongly affected by disease severity, in which is predominantly influenced by age, BMI, and comorbidity.

Abstract Background Female sexual dysfunction (FSD) is a highly prevalent health disorder and no self-report questionnaire on female sexual function is available in Romanian. Therefore we considered the Female Sexual Function Index (FSFI) to be the most appropriate due to its excellent psychometric properties. The FSFI is a measuring scale with 19 items that assess the six domains of female sexual function: desire, arousal, lubrication, orgasm, satisfaction and pain. The paper aims to analyze the psychometric reliability and validity of the FSFI-RO (Romanian Version of the Female Sexual Function Index). Methods 385 women (aged 18 to 51) enrolled in the present study. To assess the presence of FSD we used the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria for sexual dysfunction. Then we categorized the participants into two groups: the FSD group (41%) and the healthy control group (59%). Women were then asked to fill out a form that included sociodemographic information and the FSFI-RO questionnaire. A sample of 50 women agreed to re-answer FSFI-RO in a 4-week interval in order to evaluate the test-retest validity of the questionnaire. The data were summarized using descriptive statistics: the test-retest reliability was measured by the intraclass correlation coefficient (ICC); Cronbach’s alpha was employed to evaluate the internal consistency of the Romanian version of the FSFI, and validity was assessed by the content and construct validity. Results The results showed high test-retest reliability, with ICC from 0.942 to 0.991 in the domains and 0.987 in the total score. Regarding the internal consistency of the FSFI-RO, Cronbach’s α coefficients were found to be high (α = 0.944). Convergent construct validity proved to be moderate to high in desire, arousal, lubrication, orgasm and, satisfaction domains, and weak correlation in the pain domain. Regarding the discriminant construct validity, the scores for each domain and the total score showed statistically significant differences between the FSD group and the control group. Conclusions The FSFI-RO showed similar psychometric properties to those of the original version, therefore being a reliable and valid instrument that can be used in Romanian-speaking women.