Content analysis of the Measure of the Quality of the Environment by linkage with the International Classification of Functioning, Disability and Health.

BACKGROUND: This study explores the linkage between the Measurement of Environmental Quality (MQE) and the International Classification of Functioning, Disability, and Health (ICF). Stemming from the Human Development Model-Disability Creation Process (HDM-DCP), MQE enhances understanding of how environmental quality impacts disability development across diverse socio-cultural contexts. Integrating MQE with ICF expands the perspective on disability formation beyond HDM-DCP, encompassing ICF's functioning approach. OBJECTIVE: To link the MQE with the concepts and categories of the ICF. METHODS: Two health professionals with adequate taxonomic knowledge of the ICF performed the initial linkage, which was based on updated standardized rules considering all hierarchical levels of the ICF. Linkage agreement between the first two assessors was measured using the Kappa (k) coefficient and respective 95% confidence intervals. In the absence of a consensus between the two assessors (k > 0.60), a third assessor was consulted to make the arbitrary decision of the final categories linked to the MQE. RESULTS: Insufficient agreement between the two assessors was found for the linkage process (k = 0.52; p < 0.001), requiring the final decision from the third assessor. At the end of the process, 26 ICF categories were linked to the main concepts (MC) measured by the 26 items of the short version of the MQE. Ten ICF categories were linked to the additional concepts (AC) measured by the MQE. Moreover, the MQE addresses the five domains of the ICF component "environmental factors," with a predominance of the "services, systems and policies" domain (MC = 45.8% and AC = 40%). CONCLUSION: The linkage of the concepts measured by the MQE to ICF categories enabled mapping the content of the MQE, identifying it as a promising tool for measuring environmental factors in accordance with ICF percepts.

External beam radiation therapy for recurrent or residual thyroid cancer: What is the best treatment time and the best candidate for long-term local disease control?

INTRODUCTION: Cervical disease control might be challenging in advanced thyroid cancer (DTC). Indications for cervical external beam radiation therapy (EBRT) are controversial. PURPOSE: To identify clinical and molecular factors associated with control of cervical disease with EBRT. METHODS: Retrospective evaluation and molecular analysis of the primary tumor DTC patients who underwent cervical EBRT between 1995 and 2022 was performed. RESULTS: Eighty adults, median age of 61 years, were included. T4 disease was present in 43.7%, lymph node involvement in 42.5%, and distant metastasis in 47.5%. Those with cervical progression were older (62.5 vs. 57.3, p = 0.04) with more nodes affected (12.1 vs. 2.8, p = 0.04) and had EBRT performed later following surgery (76.6 vs. 64 months, p = 0.05). EBRT associated with multikinase inhibitors showed longer overall survival than EBRT alone (64.3 vs. 37.9, p = 0.018) and better local disease control. Performing EBRT before radioiodine (RAI) was associated with longer cervical progression-free survival (CPFS) than was RAI before (67.5 vs. 34.5, p < 0.01). EBRT ≥2 years after surgery was associated with worse CPFS (4.9 vs. 34, p = 0.04). The most common molecular alterations were ERBB2, BRAF, FAT1, RET and ROS1 and TERT mutation was predictive of worse disease control after EBRT (p = 0.04). CONCLUSION: Younger patients, with fewer affected nodes and treated earlier after surgery had better cervical disease control. Combination of EBRT with MKI improved OS. TERT mutation might indicate worse responders to EBRT; however, further studies are necessary to clarify the role of molecular testing in selecting candidates for cervical EBRT.

Alcohol Use and Abstinence throughout Adolescence: The Changing Contributions of Perceived Risk of Drinking, Opportunities to Drink, and Self-Control.

Objective: Adolescence is characterized by psychosocial and cognitive changes that can alter the perceived risk of negative effects of alcohol, opportunities to drink, and self-control. Few studies have investigated whether these factors change in their contribution to adolescent drinking over time. This study examined associations between perceived risk, opportunities to drink, self-control, and past-year drinking and investigated whether self-control buffers the effect of lower perceived risk and frequent drinking opportunities on the probability of past-year drinking. Method: Data from a four-wave longitudinal study (2015-2020) of 2,104 North Carolina adolescents (Mage = 12.36, SDage = 1.12, at Time 1) were used to assess changes in associations between self-control, perceived risk of drinking, and drinking opportunities on the frequency of past-year drinking. Hypotheses were tested using latent trajectory models. Results: At all timepoints, greater perceived risk, fewer drinking opportunities, and higher self-control were associated with drinking abstinence in the past year. Self-control buffered the impact of frequent drinking opportunities and lower perceived risk on the probability of alcohol use at Times 1-3. Conclusions: Despite expectations that adolescents' ability to navigate their environments improves as they age, associations between risk, protective factors, and past-year drinking were relatively stable over time. Nevertheless, self-control protected against frequent drinking opportunities and lower perceived risk. Strategies that support or relieve the need for self-control (e.g., situation modification) may protect against alcohol use throughout adolescence.

Density-based lipoprotein depletion improves extracellular vesicle isolation and functional analysis.

BACKGROUND: Blood plasma is the main source of extracellular vesicles (EVs) in clinical studies aiming to identify biomarkers and to investigate pathophysiological processes, especially regarding EV roles in inflammation and thrombosis. However, EV isolation from plasma has faced the fundamental issue of lipoprotein contamination, representing an important bias since lipoproteins are highly abundant and modulate cell signaling, metabolism, and thromboinflammation. OBJECTIVES: Here, we aimed to isolate plasma EVs after depleting lipoproteins, thereby improving sample purity and EV thromboinflammatory analysis. METHODS: Density-based gradient ultracentrifugation (G-UC) was used for lipoprotein depletion before EV isolation from plasma through size-exclusion chromatography (SEC) or serial centrifugation (SC). Recovered EVs were analyzed by size, concentration, cellular source, ultrastructure, and bottom-up proteomics. RESULTS: G-UC efficiently separated lipoproteins from the plasma, allowing subsequent EV isolation through SEC or SC. Combined analysis from EV proteomics, cholesterol quantification, and apoB-100 detection confirmed the significant reduction in lipoproteins from isolated EVs. Proteomic analysis identified similar gene ontology and cellular components in EVs, regardless of lipoprotein depletion, which was consistent with similar EV cellular sources, size, and ultrastructure by flow cytometry and transmission electron microscopy. Importantly, lipoprotein depletion increased the detection of less abundant proteins in EV proteome and enhanced thromboinflammatory responses of platelets and monocytes stimulated in vitro with EV isolates. CONCLUSION: Combination of G-UC+SEC significantly reduced EV lipoprotein contamination without interfering in EV cellular source, gene ontology, and ultrastructure, allowing the recovery of highly pure EVs with potential implications for functional assays and proteomic and lipidomic analyses.

Serum anti-Müllerian hormone is lower in patients with multiple radioiodine dose for treatment of pediatric thyroid cancer.

Introduction: Treatment of patients with pediatric differentiated thyroid cancer (DTC) often involves radioiodine (RAI), which is associated with increased risks of short- and long-term adverse outcomes. The impact of RAI treatment on the female reproductive system remains uncertain. Anti-Müllerian hormone (AMH) is a marker of ovarian reserve and is related to fertility. Objective: The aim was to analyze the association between RAI and serum AMH level in women treated with RAI. Methods: We evaluated women with pediatric DTC treated with RAI at the age of ≤19 years. Serum AMH was measured. Results: The study included 47 patients with a mean age of 25.1 years (12.4-50.8) at AMH measurement and follow-up of 11.8 ± 8.4 years. The mean RAI administered was 235 mCi (30-1150). Sixteen (34%) received multiple RAI doses (471 ± 215 mCi). Mean AMH level was 2.49 ng/mL (0.01-7.81); the level was 1.57 ng/mL (0.01-7.81) after multiple RAI doses and 2.99 ng/mL (0.01-6.63) after a single RAI dose (P = 0.01). Patients who received a cumulative RAI lower than 200 mCi had higher AMH levels (2.23 ng/mL, 0.39-7.81) than those who received more (1.0 ng/mL, 0.01-6.63; P = 0.02). In patients with similar cumulative RAI activities, administration of multiple RAI doses was significantly and independently associated with AMH level lower than the reference range for age (HR: 5.9, 1.55-52.2, P = 0.014) after age adjustments. Conclusion: Levels of AMH were lower after multiple RAI doses, especially after a cumulative RAI dose above 200 mCi. More studies are needed to clarify the impact of RAI on fertility considering its cumulative activity and treatment strategy.

Stimulated thyroglobulin and diagnostic 131-iodine whole-body scan as a predictor of distant metastasis and association with response to treatment in pediatric thyroid cancer patients.

INTRODUCTION: Differentiated thyroid carcinoma (DTC) is a rare oncological disease in the pediatric population, presenting with a more aggressive form. Stimulated thyroglobulin (sTg) and the 131-iodine whole-body scans (WBSs) are known adult markers related to the presence of distant metastasis. Little is known about their roles in the pediatric population. PURPOSE: To evaluate sTg levels and diagnostic WBS (DxWBS) as predictors of distant metastasis after thyroidectomy and to correlate with the response to treatment at the end of follow-up in pediatric DTC. MATERIALS AND METHODS: Patients under 19 years old diagnosed with DTC from 1980 to 2022 were retrospectively evaluated. sTg values and WBS were assessed after thyroidectomy and prior radioiodine treatment (RIT) and correlated with the possibility of finding distant metastasis and response to treatment at the end of follow-up. RESULTS: In a total of 142 patients with a median age of 14.6 (4-18) years who were followed for 9.5 ± 7.2 years and classified according to the ATA risk of recurrence as low (28%), intermediate (16%), and high risk (56%), 127 patients had their sTg evaluated. A sTg value of 21.7 ng/dl yielded a sensitivity of 88% compared to 30% for DxWBS in predicting distant metastasis. Specificity was 60% and 100% respectively. 42% of patients obtained discordant results between DxWBS and RxWBS. In high-risk patients, sTg levels were particularly able to differentiate those who would have distant metastasis with better diagnostic accuracy than the WBSs. CONCLUSIONS: The sTg level had better performance in detecting distant metastases in pediatric DTC than the DxWBS. DxWBS's low performance suggests that caution should be taken in interpreting their findings in terms of the underdiagnosis for metastatic disease, especially when the sTg level already suggests distant disease.

Challenges and Applications of Genetic Testing in Dilated Cardiomyopathy: Genotype, Phenotype and Clinical Implications. / Desafios e Aplicações dos Testes Genéticos na Cardiomiopatia Dilatada: Genótipo, Fenótipo e Implicações Clínicas.

Genetic tests for dilated cardiomyopathy (DCM) have a diagnostic yield of up to 40%, but there is significant genetic heterogeneity and other challenges, such as variable expressivity and incomplete penetrance. Pedigree analysis is essential for distinguishing between sporadic and familial DCM cases by assessing family history. Familial DCM yields higher results in genetic testing, but sporadic DCM does not rule out the possibility of a genetic cause. Some genes have specific phenotypes, with the Lamin gene ( LMNA ) being associated with a phenotype of malignant arrhythmias and advanced heart failure (HF). The presence of a causal genetic variant can also aid in prognostic evaluation, identifying more severe cases with lower rates of reverse remodeling (RR) compared to individuals with a negative genotype. Current guidelines recommend genetic evaluation and counseling for individuals with DCM, along with cascade screening in first-degree relatives in cases where one or more variants are identified, offering an opportunity for early diagnosis and treatment. Relatives with a positive genotype and negative phenotype are candidates for serial evaluation, with frequency varying by age. Genotype also assists in individualized recommendations for implantable cardioverter-defibrillator (ICD) placement and advice regarding physical activity and family planning. Ongoing studies are progressively elucidating the details of genotype/phenotype relationships for a large number of variants, making molecular genetics increasingly integrated into clinical practice.

Os testes genéticos para cardiomiopatia dilatada (CMD) apresentam uma positividade de até 40%, mas há uma grande heterogeneidade genética e outros desafios decorrentes de expressividade variável e penetrância incompleta. O heredograma é fundamental para diferenciar os casos de CMD esporádica e familiar, por meio da avaliação do histórico familiar. A CMD familiar apresenta um rendimento maior nos testes genéticos, mas a CMD esporádica não exclui a possibilidade de causa genética. Alguns genes têm fenótipos específicos, sendo o gene da Lamina ( LMNA ) o mais fortemente associado a um fenótipo de arritmias malignas e quadros de insuficiência cardíaca (IC) avançada. A presença de uma variante genética causal também pode ajudar na avaliação prognóstica, identificando quadros mais graves e com menores taxas de remodelamento reverso em comparação com indivíduos com genótipo negativo. As diretrizes atuais recomendam a avaliação e aconselhamento genético em indivíduos com CMD, além do rastreamento em cascata nos familiares de primeiro grau nos casos em que há uma ou mais variantes identificadas, sendo uma oportunidade para o diagnóstico e tratamento precoces. Familiares com genótipo positivo e fenótipo negativo são candidatos à avaliação seriada, com periodicidade que varia conforme a idade. O genótipo também auxilia na indicação individualizada de cardiodesfibrilador implantável e em recomendações quanto à atividade física e planejamento familiar. Estudos em curso esclarecem progressivamente os detalhes das relações genótipo/fenótipo de um grande número de variantes e fazem com que a genética molecular esteja cada vez mais presente na prática clínica.

Identity Matters: Multiple Herbivory Induces Less Attractive or Repellent Coffee Plant Volatile Emission to Different Natural Enemies.

Co-infestations by herbivores, a common situation found in natural settings, can distinctly affect induced plant defenses compared to single infestations. Related tritrophic interactions might be affected through the emission of changed blends of herbivore-induced plant volatiles (HIPVs). In a previous study, we observed that the infestation by red spider mite (Oligonychus ilicis) on coffee plants facilitated the infestation by white mealybug (Planococcus minor), whereas the reverse sequence of infestation did not occur. Here, we examined the involvement of the jasmonate and salicylate pathways in the plant-mediated asymmetrical facilitation between red spider mites and white mealybugs as well as the effect of multiple herbivory on attractiveness to the predatory mite Euseius concordis and the ladybug Cryptolaemus montrouzieri. Both mite and mealybug herbivory led to the accumulation of JA-Ile, JA, and cis-OPDA in plants, although the catabolic reactions of JA-Ile were specifically regulated by each herbivore. Infestation by mites or mealybugs induced the release of novel volatiles by coffee plants, which selectively attracted their respective predators. Even though the co-infestation by mites and mealybugs resulted in a stronger accumulation of JA-Ile, JA and SA than the single infestation treatments, the volatile emission was similar to that of mite-infested or mealybug-infested plants. However, multiple infestation had a negative impact on the attractiveness of HIPVs to the predators, making them less attractive to the predatory mite and a repellent to the ladybug. We discuss the potential underlying mechanisms of the susceptibility induced by mites, and the effect of multiple infestation on each predator.

Optimization of Statin-Loaded Delivery Nanoparticles for Treating Chronic Liver Diseases by Targeting Liver Sinusoidal Endothelial Cells.

In this study, we developed functionalized polymeric micelles (FPMs) loaded with simvastatin (FPM-Sim) as a drug delivery system to target liver sinusoidal endothelial cells (LSECs) for preserving liver function in chronic liver disease (CLD). Polymeric micelles (PMs) were functionalized by coupling peptide ligands of LSEC membrane receptors CD32b, CD36 and ITGB3. Functionalization was confirmed via spectroscopy and electron microscopy. In vitro and in vivo FPM-Sim internalization was assessed by means of flow cytometry in LSECs, hepatocytes, Kupffer and hepatic stellate cells from healthy rats. Maximum tolerated dose assays were performed in healthy mice and efficacy studies of FPM-Sim were carried out in bile duct ligation (BDL) and thioacetamide (TAA) induction rat models of cirrhosis. Functionalization with the three peptide ligands resulted in stable formulations with a greater degree of in vivo internalization in LSECs than non-functionalized PMs. Administration of FPM-Sim in BDL rats reduced toxicity relative to free simvastatin, albeit with a moderate portal-pressure-lowering effect. In a less severe model of TAA-induced cirrhosis, treatment with FPM-CD32b-Sim nanoparticles for two weeks significantly decreased portal pressure, which was associated with a reduction in liver fibrosis, lower collagen expression as well as the stimulation of nitric oxide synthesis. In conclusion, CD32b-FPM stands out as a good nanotransporter for drug delivery, targeting LSECs, key inducers of liver injury.

Bacterial Polyhydroxyalkanoates-based Therapeutics-delivery Nanosystems.

Microbial polyhydroxyalkanoates (PHAs) are bio-based aliphatic biopolyester produced by bacteria as an intracellular storage material of carbon and energy under stressed conditions. PHAs have been paid attention to due to their unique and impressive biological properties including high biodegradability, biocompatibility, low cytotoxicity, and different mechanical properties. Under this context, the development of drug-delivery nanosystems based on PHAs has been revealed to have numerous advantages compared with synthetic polymers that included biocompatibility, biodegradability, non-toxic, and low-cost production, among others. In this review article, we present the available state of the art of PHAs. Moreover, we discussed the potential benefits, weaknesses, and perspectives of PHAs to the develop drug delivery systems.

Trigger Finger or De Quervain Tenosynovitis after Surgical Treatment for Carpal Tunnel Syndrome.

Objective To evaluate the open surgical treatment for carpal tunnel syndrome as a risk factor for the development of stenosing tenosynovitis that results in trigger finger and De Quervain disease. Materials and Methods A retrospective study analyzing the medical records of patients submitted to open surgical release of carpal tunnel syndrome between 2010 and 2021 in a secondary- and tertiary-level hospital. The following data were collected: pathological history, duration of the follow-up after the surgical treatment for carpal tunnel syndrome, development of trigger finger or De Quervain tenosynovitis, affected fingers, and the interval between the end of surgery and symptom onset. Results We evaluated 802 patients of both genders and with a mean age of 50.1 (±12.6) years. The mean follow-up was of 13 (±16.4) months. The mean time until the development of trigger finger was of 61.4 months, and of 73.7 months for De Quervain disease. The incidence of development of De Quervain disease was of 4.12%, and for trigger finger it was of 10.2%. The most affected digits were the thumb (47.6%), the middle (24.4%), and the ring finger (8.54%). Age was the only factor that showed an association with the risk of developing trigger finger, with an increase of 2% for each increase in age of 1 year. Conclusion The incidence rates for the development of De Quervain disease (4.12%) and trigger finger (10.2%) after the surgical treatment for carpal tunnel syndrome were like those described in the literature. Only age was a factor that influenced the development of trigger finger.

Trigger Finger or De Quervain Tenosynovitis after Surgical Treatment for Carpal Tunnel Syndrome / Dedo em gatilho ou tenossinovite de De Quervain após tratamento cirúrgico da síndrome do túnel do carpo

Abstract Objective To evaluate the open surgical treatment for carpal tunnel syndrome as a risk factor for the development of stenosing tenosynovitis that results in trigger finger and De Quervain disease. Materials and Methods A retrospective study analyzing the medical records of patients submitted to open surgical release of carpal tunnel syndrome between 2010 and 2021 in a secondary- and tertiary-level hospital. The following data were collected: pathological history, duration of the follow-up after the surgical treatment for carpal tunnel syndrome, development of trigger finger or De Quervain tenosynovitis, affected fingers, and the interval between the end of surgery and symptom onset. Results We evaluated 802 patients of both genders and with a mean age of 50.1 (±12.6) years. The mean follow-up was of 13 (±16.4) months. The mean time until the development of trigger finger was of 61.4 months, and of 73.7 months for De Quervain disease. The incidence of development of De Quervain disease was of 4.12%, and for trigger finger it was of 10.2%. The most affected digits were the thumb (47.6%), the middle (24.4%), and the ring finger (8.54%). Age was the only factor that showed an association with the risk of developing trigger finger, with an increase of 2% for each increase in age of 1 year. Conclusion The incidence rates for the development of De Quervain disease (4.12%) and trigger finger (10.2%) after the surgical treatment for carpal tunnel syndrome were like those described in the literature. Only age was a factor that influenced the development of trigger finger.

Resumo Objetivo Avaliar o tratamento cirúrgico aberto da síndrome do túnel do carpo como fator de risco para o desenvolvimento das tenossinovites estenosantes formadoras do dedo em gatilho e da doença de De Quervain. Materiais e Métodos Estudo retrospectivo com análise dos prontuários de pacientes submetidos a liberação cirúrgica aberta da síndrome do túnel do carpo entre 2010 e 2021 em hospital de níveis secundário e terciário. Os seguintes dados foram coletados: histórico patológico, tempo de acompanhamento após o tratamento cirúrgico da síndrome do túnel do carpo, desenvolvimento de dedo em gatilho ou tenossinovite de De Quervain, dedos acometidos, e tempo decorrido entre o fim da cirurgia e o aparecimento dos sintomas. Resultados Foram avaliados 802 pacientes de ambos os sexos com média de idade de 50,1 (±12,6) anos. O tempo médio de seguimento foi de 13 (±16,4) meses. O tempo médio de desenvolvimento de dedo em gatilho foi de 61,4 meses, e o da doença de De Quervain, de 73,7 meses. A incidência de desenvolvimento da doença de De Quervain foi de 4,12% e a de dedo em gatilho, de 10,2%. Os dedos mais acometidos foram o polegar (47,6%), o médio (24,4%) e o anular (8,54%). A idade foi único fator que demonstrou associação com o risco de desenvolvimento de dedo em gatilho, com aumento de 2% a cada ano a mais de idade. Conclusão As taxas de incidência de desenvolvimento de doença de De Quervain (4,12%) e de dedo em gatilho (10,2%) após tratamento cirúrgico da síndrome do túnel do carpo foram semelhantes às descritas na literatura. Apenas a idade se apresentou como fator influenciador no desenvolvimento de dedo em gatilho.

Adhesive Capsulitis' Patients Report Improvement in Functionality Trough International Classification of Functioning, Disability and Health Checklist and Dash After Suprascapular Nerve Blocks.

Objective To evaluate the functionality in patients with adhesive capsulitis undergoing suprascapular nerve block (SSNB). Methods A before-and-after clinical prospective study in a single center was conducted with patients with secondary adhesive capsulitis treated with four nerve blocks based on anatomical limits. The sample was non-probabilistic, and it was obtained after a routine appointment at a specialized outpatient clinic. The instruments used for evaluation were the International Classification of Functioning, Disability and Health (ICF) and the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, which were applied at baseline (T 0 ), one week after the fourth SSNB (T 4 ), and three months after the first SSNB (T 12 ). The paired t -test was used to compare the means of the ICF checklist items and DASH in the different: T 0 xT 4 ; T 4 xT 12 ; and T 0 xT 12 ). The probability of rejecting the null hypothesis was 5%. Results The sample was composed of 25 individuals with a mean age of 58.16 years; 16 of them were female. The duration of the pain symptoms ranged from 2 to 16 months, with a mean of 5.92 months. The ICF checklist showed that all domains had already improved in T 4, except for the environmental factors, which only improved at 03 months ( p = 0.037). The patients reported improvements in shoulder function in T 4 , which increased more in T 12 , at the end of data collection ( p = 0.019). Conclusion The SSNB technique is effective in patients with adhesive capsulitis after 4 weeks of application, with improvements in individual's functionality lasting for 12 weeks.

Identifying modifiable factors associated with psychological health in women experiencing infertility.

This study assessed the relationship between modifiable psychological variables and depression, anxiety, and posttraumatic growth in women experiencing infertility. U.S. women (N = 457) who identified as experiencing infertility completed standardized self-report measures of mindfulness, self-compassion, positive affect, intolerance of uncertainty, relationship satisfaction, experiential avoidance, depression, anxiety, and posttraumatic growth. Clinical and demographic characteristics (age, duration trying to conceive, miscarriage, and childlessness) did not predict depression or anxiety. Lower positive affect and higher experiential avoidance were associated with depression and anxiety. Lower self-compassion was associated with depression; higher intolerance of uncertainty was associated with anxiety. There were indirect effects of mindfulness on anxiety and depression via these variables. Future research should explore whether intervening on these factors reduces depressive and anxiety symptoms. Promoting mindfulness may have beneficial effects on symptoms via its downstream effects on multiple coping variables. Counterintuitively, posttraumatic growth was associated with higher intolerance of uncertainty and experiential avoidance.

The Nanotechnology-Based Approaches against Kirsten Rat Sarcoma-Mutated Cancers.

Kirsten rat sarcoma (KRAS) is a small GTPase which acts as a molecular switch to regulate several cell biological processes including cell survival, proliferation, and differentiation. Alterations in KRAS have been found in 25% of all human cancers, with pancreatic cancer (90%), colorectal cancer (45%), and lung cancer (35%) being the types of cancer with the highest mutation rates. KRAS oncogenic mutations are not only responsible for malignant cell transformation and tumor development but also related to poor prognosis, low survival rate, and resistance to chemotherapy. Although different strategies have been developed to specifically target this oncoprotein over the last few decades, almost all of them have failed, relying on the current therapeutic solutions to target proteins involved in the KRAS pathway using chemical or gene therapy. Nanomedicine can certainly bring a solution for the lack of specificity and effectiveness of anti-KRAS therapy. Therefore, nanoparticles of different natures are being developed to improve the therapeutic index of drugs, genetic material, and/or biomolecules and to allow their delivery specifically into the cells of interest. The present work aims to summarize the most recent advances related to the use of nanotechnology for the development of new therapeutic strategies against KRAS-mutated cancers.

The association between evening social media use and delayed sleep may be causal: Suggestive evidence from 120 million Reddit timestamps.

Public health officials and clinicians routinely advise social media users to avoid nighttime social media use due to the perception that this delays the onset of sleep and predisposes to the health risks of insufficient sleep. With some exceptions, the evidence behind this advice mostly derives from surveys identifying an association between self-reported social media usage and self-reported sleep patterns. In principle, these associations could alternatively be explained by users turning to social media to pass the time when they are otherwise having difficulty sleeping, or by individual differences that draw some people to frequent social media use, or by offline activities that overlap with both social media use and delayed sleep. To attempt to distinguish among these explanations, we leveraged estimated bedtimes from 44,000 Reddit users reported in a recent study and their 120 million posts to test whether the relationship between sleep and social media has properties suggestive of a causal relationship. We find that users are especially likely to be active on Reddit after their bedtime (and therefore awake) on nights that they posted to Reddit shortly before bedtime, especially if they posted multiple times or in high-engagement forums that night. Overall, this study lends additional support to the notion that there likely is some causal effect of evening social media use on delayed sleep onset.

Adhesive Capsulitis' Patients Report Improvement in Functionality Trough International Classification of Functioning, Disability and Health Checklist and Dash After Suprascapular Nerve Blocks / Pacientes com capsulite adesiva relatam melhora da funcionalidade pela Classificação Internacional de Funcionalidade, Incapacidade e Saúde e DASH após bloqueios do nervo supraescapular

Abstract Objective To evaluate the functionality in patients with adhesive capsulitis undergoing suprascapular nerve block (SSNB). Methods A before-and-after clinical prospective study in a single center was conducted with patients with secondary adhesive capsulitis treated with four nerve blocks based on anatomical limits. The sample was non-probabilistic, and it was obtained after a routine appointment at a specialized outpatient clinic. The instruments used for evaluation were the International Classification of Functioning, Disability and Health (ICF) and the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, which were applied at baseline (T0), one week after the fourth SSNB (T4), and three months after the first SSNB (T12). The paired t-test was used to compare the means of the ICF checklist items and DASH in the different: T0xT4;T4xT12;and T0xT12). The probability of rejecting the null hypothesis was 5%. Results The sample was composed of 25 individuals with a mean age of 58.16 years; 16 of them were female. The duration of the pain symptoms ranged from 2 to 16 months, with a mean of 5.92 months. The ICF checklist showed that all domains had already improved in T4 except for the environmental factors, which only improved at 03 months (p = 0.037). The patients reported improvements in shoulder function in T4, which increased more in T12, at the end of data collection (p = 0.019). Conclusion The SSNB technique is effective in patients with adhesive capsulitis after4 weeks of application, with improvements in individual's functionality lasting for 12 weeks.

Resumo Objetivo Avaliar a funcionalidade em pacientes com capsulite adesiva submetidos a bloqueio do nervo supraescapular (BNSE). Métodos Um estudo clínico prospectivo do tipo antes e depois foi realizado em um único centro com pacientes com capsulite adesiva secundária tratados com quatro bloqueios baseados em limites anatômicos. A amostra foi não probabilística, tendo sido obtida após consulta de rotina em ambulatório especializado. Os instrumentos utilizados para avaliação foram a Classificação Internacional de Funcionalidade, Incapacidade e Saúde (CIF) e o questionário de Disfunções do Braço, Ombro e Mão (DASH), que foram aplicados antes da intervenção (T0), uma semana após o quarto BNSE (T4),etrêsapósoprimeiroBNSE(T12).AsmédiasdositensdaCIFedoDASHnos diferentes tempos (T0 x T4; T4 x T12; e T0 x T12) foram comparadas por meio do teste t pareado. A probabilidade de rejeitar a hipótese nula foi de 5%. Resultados A amostra foi composta por 25 indivíduos com média de idade de 58,16 anos; 16 eram mulheres. A duração dos sintomas dolorosos variou de 2 a 16 meses, com média de 5,92 meses. A CIF mostrou que todos os domínios já haviam melhorado em T4 à exceção dos fatores ambientais, que só melhoraram aos 3 meses (p = 0,037). Os pacientes já relataram melhora na função do ombro em T4 emaisainda em T12,ao finaldacoletadedados (p = 0,019). Conclusão A técnica de BNSE é eficaz em pacientes com capsulite adesiva após 4 semanas de aplicação, com melhora da funcionalidade do indivíduo e sua manutenção até 12 semanas.

Intervening on Social Comparisons on Social Media: Electronic Daily Diary Pilot Study.

BACKGROUND: Literature has underscored the dark aspects of social media use, including associations with depressive symptoms, feelings of social isolation, and diminished self-esteem. Social comparison, the process of evaluating oneself relative to another person, is thought to contribute to these negative experiences such that people with a stronger tendency to compare themselves with others are particularly susceptible to the detrimental effects of social media. Social media as a form of social connection and communication is nevertheless an inevitable-and arguably integral-part of life, particularly for young adults. Therefore, there is a need to investigate strategies that could alter the manner in which people interact with social media to minimize its detrimental effects and maximize the feelings of affiliation and connection. OBJECTIVE: This pilot study examined the feasibility, acceptability, and effectiveness of a brief web-based intervention designed to alter engagement with social media and promote psychological well-being by encouraging social savoring as an alternative to social comparison. Social savoring was operationalized as experiencing joyful emotions related to the happiness of someone else's experiences (ie, feeling happy for someone else). METHODS: Following an intensive longitudinal design, 55 college students (mean age 19.29, SD 0.93 years; n=43, 78% women and n=23, 42% White) completed baseline measures (individual differences, psychological well-being, connectedness, and social media use) and then 14 days of daily surveys on their social media activity and well-being. On day 8, the group that was randomized to receive the intervention watched a video instructing them on the skill of social savoring and was asked to practice this skill during days 8 to 14. RESULTS: Overall, participants reported positive perceptions of the intervention. Participants who watched the intervention video reported significantly higher performance self-esteem (P=.02) at posttest than those in the control condition, after controlling for baseline levels. Participants also reported significantly higher state self-esteem (P=.01) on days in which they engaged in more social savoring while using social media, and the use of social savoring increased significantly (P=.01) over time, suggesting that participants found it helpful. Participants in both conditions reported significantly lower levels of social comparison (control: P=.01; intervention: P=.002) and higher levels of connectedness (control: P<.001; intervention: P=.001) at posttest than at baseline. CONCLUSIONS: Initial evidence from this pilot study suggests that a web-based social savoring intervention may help minimize the potentially harmful consequences of social media use, at least in some domains. Future work is needed to examine the effectiveness and acceptance of this intervention in different age groups and in clinical samples that are in part characterized by higher levels of comparison with others (eg, people with eating disorders).

Digital location tracking: A preliminary investigation of parents' use of digital technology to monitor their adolescent's location.

The emergence of digital technologies has changed the dynamic of parent-adolescent relationships. Parents can now use digital technologies to monitor their adolescent's physical location. Yet, to date, no known research has examined the extent to which digital location tracking occurs in parent-adolescent dyads, and how tracking links to adolescent adjustment. The current research examined digital location tracking in a large sample of adolescents (N = 729; Mage = 15.03). Overall, about half of parents and adolescents reported digital location tracking. Girls and younger adolescents were more likely to be tracked, and tracking was associated with greater externalizing problems and alcohol consumption; however, these associations were not robust across multiple informants and sensitivity analyses. Positive linkages with externalizing problems and cannabis use were in part contingent on age and positive parenting, with associations emerging for older adolescents and adolescents who report lower positive parenting. Older adolescents are increasingly striving for independence and autonomy, and adolescents who perceive lower positive parenting may view digital tracking as controlling and intrusive. However, results were not robust after statistical correction. This brief report is intended to serve as a preliminary investigation into digital location tracking, and future research is needed to determine the directionality of associations. Possible consequences of parental digital tracking require careful consideration by researchers in order to provide guidance on the best practices for engaging in digital monitoring while nurturing and respecting the parent-adolescent relationship. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Neutrophil-to-lymphocyte ratio as an independent factor for worse prognosis in radioiodine refractory thyroid cancer patients.

PURPOSE: This study aimed to evaluate neutrophil to lymphocyte ratio (NLR) as a laboratory biomarker in radioactive iodine-refractory (RAIR) locally advanced and/or metastatic differentiated thyroid cancer (DTC) and determine its correlation with overall survival (OS). METHODS: We retrospectively included 172 patients with locally advanced and/or metastatic RAIR DTC admitted between 1993 and 2021 at INCA. Age at diagnosis, histology, presence of distant metastasis (DM), DM site, neutrophil-to- lymphocyte ratio (NLR), imaging studies such as PET/CT results, progression free survival (PFS) and overall survival (OS) data were analyzed. NLR was calculated at the time of locally advanced and/or metastatic disease diagnosis and the cutoff value was 3. Survival curves were established using the Kaplan-Meier method. The confidence interval is 95%, and a p-value of less than 0.05 was considered statistically significant RESULTS: Out of 172 patients, 106 were locally advanced, and 150 presented DM at some point during follow-up. Regarding NLR data, 35 had NLR over 3 and 137 had NLR under 3. Higher NLR at was associated with shorter OS (6 vs. 10; p = 0.05) and with highest SUV on FDG PET-CT (15.9 vs. 7.7, p = 0.013). We found no association between higher NLR and age at diagnosis, DM or final status. CONCLUSION: NLR higher than 3 at the time of locally advanced and/or metastatic disease diagnosis is an independent fator for shorter OS in RAIR DTC patients. Noteworthy higher NLR was also associated with highest SUV on FDG PET-CT in this population.