Effectiveness and safety of neoadjuvant therapy in triple-negative breast cancer in a real-world population.

OBJECTIVE: Triple-negative breast cancer is a subtype of aggressive breast cancer. Our aim is to evaluate the effectiveness and safety of neoadjuvant treatment in early-stage triple-negative breast cancer and to identify predictors of pathological complete response. METHODS: This is a single-center, retrospective study involving 79 patients with triple-negative breast cancer who initiated neoadjuvant treatment between January 2017 and October 2022. Descriptive analyses were performed as appropriate. Statistical analysis utilized bivariate logistic regression to explore the presence of factors related to pathological complete response, and the Kaplan-Meier method was employed for survival analysis. RESULTS: In the overall population, 27 patients (n=78; 34.6%) achieved pathological complete response in the breast and axillary lymph nodes, and 31 (n=73; 42.5%) achieved a grade 5 pathological complete response in the breast, according to the Miller and Payne classification. The addition of platinum to standard therapy improved both breast and axillary lymph node pathological complete response rates. Age less than 40 years was identified as a predictor of pathological complete response in our study population through bivariate analysis, while Ki67 levels lower than 70% were associated with a lower pathological complete response rate. Adverse events were reported in 72 patients (91.1%), with grade 3-5 adverse events observed in 33 (41.8%). There was a particularly notable increase in gastrointestinal and hematological adverse events when platinum was added. CONCLUSIONS: In this population, we observed moderate rates of pathological complete response with acceptable chemotherapy tolerance. Platinum-based chemotherapy appears to enhance the likelihood of achieving pathological complete response, albeit with a less favorable safety profile. Therefore, evaluating the benefit-risk balance is crucial when selecting the optimal chemotherapy regimen for individual patients.

Aberrant salience mediates the interplay between emotional abuse and positive symptoms in schizophrenia.

INTRODUCTION: Childhood trauma and adversities (CTA) and aberrant salience (AS) have a pivotal role in schizophrenia development, but their interplay with psychotic symptoms remains vague. We explored the mediation performed by AS between CTA and psychotic symptomatology in schizophrenia. METHODS: We approached 241 adults suffering from schizophrenia spectrum disorders (SSDs), who have been in the unit for at least 12 consecutive months, excluding the diagnosis of dementia, and recent substance abuse disorder, and cross-sectional evaluated through the Aberrant Salience Inventory (ASI), Childhood Trauma Questionnaire Short-Form (CTQ-SF), and Positive and Negative Symptom Scale (PANSS). We tested a path-diagram where AS mediated the relationship between CTA and psychosis, after verifying each measure one-dimensionality through confirmatory factor analysis. RESULTS: The final sample comprised 222 patients (36.9% female), with a mean age of 42.4 (± 13.3) years and an average antipsychotic dose of 453.6 (± 184.2) mg/day (chlorpromazine equivalents). The mean duration of untreated psychosis was 1.8 (± 2.0) years while the mean onset age was 23.9 (± 8.2) years. Significant paths were found from emotional abuse to ASI total score (ß = 0.39; p < .001) and from ASI total score to PANSS positive (ß = 0.17; p = .019). Finally, a statistically significant indirect association was found from emotional abuse to PANSS positive mediated by ASI total score (ß = 0.06; p = .041; CI 95% [0.01, 0.13]). CONCLUSION: Emotional abuse has an AS-mediated effect on positive psychotic symptomatology. AS evaluation could allow a better characterization of psychosis as well as explain the presence of positive symptoms in adults with SSDs who experienced CTA.

Validation and assessment of psychometric properties of the Greek Eating Behaviors Assessment for Obesity (GR-EBA-O).

INTRODUCTION: With increasing morbidity and risk of death, obesity has become a serious health problem largely attributable to difficulties in finding proper treatments for related diseases. Many studies show how detecting abnormal eating behaviors could be useful in developing effective clinical treatments. This study aims at validating the Greek version of the Eating Behaviors Assessment for Obesity (EBA-O). METHOD: After a double English/Greek forward/backward translation of the EBA-O, 294 participants completed the Greek version (GR-EBA-O), the Eating Disorder Examination Questionnaire, the Binge Eating Scale, and the Yale Food Addiction Scale. Confirmatory factor analysis (CFA) and construct validity were calculated, and Two-way MANOVA was computed with the factors of GR-EBA-O controlling for sex and BMI categories. RESULTS: CFA confirmed the second-order five factors (i.e., food addiction, night eating, binge eating, sweet eating, and prandial hyperphagia) structure of the original EBA-O with excellent fit indices. GR-EBA-O factors were highly correlated. The GR-EBA-O subscales were also significantly correlated with the remaining measures, demonstrating good concurrent validity. CONCLUSION: The Greek version of the EBA-O has demonstrated sound psychometric properties and appears a reliable and user-friendly tool to identify pathological eating behaviors in obesity. LEVEL OF EVIDENCE: V, descriptive research.

Sarcomatoid Dedifferentiation as a Predictor of Cancer-Specific Mortality in Surgically Treated Localized Renal Cell Carcinoma.

BACKGROUND: In contemporary surgically treated patients with localized high-grade (G3 or G4) clear-cell renal cell carcinoma (ccRCC), it is not known whether presence of sarcomatoid dedifferentiation is an independent predictor and/or an effect modifier, when cancer-specific mortality (CSM) represents an endpoint. METHODS: Within the Surveillance, Epidemiology, and End Results database, all surgically treated localized high-grade ccRCC patients treated between 2010 and 2020 were identified. Univariable and multivariable Cox-regression models were used. RESULTS: In 18,853 surgically treated localized high-grade (G3 or G4) ccRCC patients, 5-year CSM-free survival was 87% (62% vs. 88% with vs. without sarcomatoid dedifferentiation, p < 0.001). Presence of sarcomatoid dedifferentiation was an independent predictor of higher CSM (hazard ratio [HR] 1.8, p < 0.001). In univariable survival analyses predicting CSM, presence versus absence of sarcomatoid dedifferentiation in G3 versus G4 yielded the following hazard ratios: HR 1.0 in absent sarcomatoid dedifferentiation in G3; HR 2.7 (p < 0.001) in absent sarcomatoid dedifferentiation in G4; HR 3.9 (p < 0.001) in present sarcomatoid dedifferentiation in G3; HR 5.1 (p < 0.001) in present sarcomatoid dedifferentiation in G4. Finally, in multivariable Cox-regression analyses, the interaction terms defining present versus absent sarcomatoid dedifferentiation in G3 versus G4 represented independent predictors of higher CSM. CONCLUSIONS: In contemporary surgically treated patients with localized high-grade ccRCC, sarcomatoid dedifferentiation is not only an independent multivariable predictor of higher CSM, but also interacts with tumor grade and results in even better ability to predict CSM.

The standardization of a new Explicit Pornographic Picture Set (EPPS).

Pictures with affective content have been extensively used in scientific studies of emotion and sexuality. However, only a few standardized picture sets have been developed that offer explicit images, with most lacking pornographic pictures depicting diverse sexual practices. This study aimed to fill this gap through developing a standardized affective set of diverse pornographic pictures (masturbation, oral sex, vaginal sex, anal sex, group sex, paraphilia) of same-sex and opposite-sex content, offering dimensional affective ratings of valence, arousal, and dominance, as well as co-elicited discrete emotions (disgust, moral and ethical acceptance). In total, 192 pornographic pictures acquired from online pornography platforms and 24 control IAPS images have been rated by 319 participants (Mage = 22.66, SDage = 4.66) with self-reported same- and opposite-sex sexual attraction. Stimuli were representative of the entire affective space, including positively and negatively perceived pictures. Participants showed differential affective perception of pornographic pictures according to gender and sexual attraction. Differences in affective ratings related to participants' gender and sexual attraction, as well as stimuli content (depicted sexual practices and sexes). From the stimuli set, researchers can select explicit pornographic pictures based on the obtained affective ratings and technical parameters (i.e., pixel size, luminosity, color space, contrast, chromatic complexity, spatial frequency, entropy). The stimuli set may be considered a valid tool of diverse explicit pornographic pictures covering the affective space, in particular, for women and men with same- and opposite-sex sexual attraction. This new explicit pornographic picture set (EPPS) is available to the scientific community for non-commercial use.

Variables predictoras del uso de los métodos anticonceptivos en jóvenes: una revisión sistemática / Predictor variables of contraceptive method use in young people: A systematic review

Diseño: Revisión sistemática. Fuentes de datos: Se consultaron las bases de datos PubMed, CINAHL, Scopus, Cuiden Plus, LILACS e IME. Selección de estudios: Se realizó una evaluación de la calidad de los estudios que fue revisada por dos investigadores en paralelo. Como resultado, se seleccionaron un total de cinco investigaciones primarias. Extracción de datos: Se extrajo información sobre la población seleccionada en el estudio, método anticonceptivo estudiado y las variables predictoras identificadas. Resultados: Se identificaron siete variables predictoras que explican específicamente el uso del preservativo masculino, píldora anticonceptiva o píldora anticonceptiva de emergencia. Las variables más relevantes fueron el nivel de conocimiento y las actitudes hacia el empleo de los métodos anticonceptivos, de manera que un mayor conocimiento y unas actitudes positivas incrementan la probabilidad de uso de métodos anticonceptivos. Otro resultado destacado fue la presencia de un sesgo formativo con un mayor conocimiento de las mujeres sobre las opciones anticonceptivas hormonales y actitudes más positivas. Conclusión: Los futuros programas formativos deben orientarse hacia la evaluación de cambios en el comportamiento, mediante el desarrollo de actitudes positivas hacia el uso de los métodos anticonceptivos a través de la adquisición de un conocimiento de calidad sobre las opciones contraceptivas.(AU)

Objective: To analyse predictor variables of contraceptive method use in young people. Design: Systematic review. Data sources: PubMed, CINAHL, Scopus, Cuiden Plus, LILACS and IME databases were consulted. Study selection: An assessment of the quality of studies was carried out by two researchers in parallel. As a result, a total of 5 primary research studies were selected. Data extraction: Information was extracted on the selected study population, contraceptive method studied and predictor variables identified. Results: Seven predictor variables were identified that specifically explain the use of the male condom, contraceptive pill or emergency contraceptive pill. The most relevant variables were the level of knowledge and attitudes towards contraceptive use, therefore high knowledge and positive attitudes increase the likelihood of contraceptive use. Another notable finding was the presence of a formative bias with womenhaving higher knowledge of hormonal contraceptive options and more positive attitudes. Conclusion: Future training programs should be oriented towards assessing behavioral changes through the development of positive attitudes towards contraceptive use by gaining knowledge of contraceptive options.(AU)

Monkeypox virus genomic accordion strategies.

The 2023 monkeypox (mpox) epidemic was caused by a subclade IIb descendant of a monkeypox virus (MPXV) lineage traced back to Nigeria in 1971. Person-to-person transmission appears higher than for clade I or subclade IIa MPXV, possibly caused by genomic changes in subclade IIb MPXV. Key genomic changes could occur in the genome's low-complexity regions (LCRs), which are challenging to sequence and are often dismissed as uninformative. Here, using a combination of highly sensitive techniques, we determine a high-quality MPXV genome sequence of a representative of the current epidemic with LCRs resolved at unprecedented accuracy. This reveals significant variation in short tandem repeats within LCRs. We demonstrate that LCR entropy in the MPXV genome is significantly higher than that of single-nucleotide polymorphisms (SNPs) and that LCRs are not randomly distributed. In silico analyses indicate that expression, translation, stability, or function of MPXV orthologous poxvirus genes (OPGs), including OPG153, OPG204, and OPG208, could be affected in a manner consistent with the established "genomic accordion" evolutionary strategies of orthopoxviruses. We posit that genomic studies focusing on phenotypic MPXV differences should consider LCR variability.

Patients' perception of using telehealth for consultation: insights after pandemic and development of an online calculator platform to predict acceptance of remote consultation: the TELEMED international study.

The COVID-19 pandemic has led to a change in healthcare models. The aim of this study was to evaluate patient acceptance of telehealth as an alternative to physical consultations, and to identify factors predicting higher satisfaction. This was an observational, cross-sectional, multi-center, international study. All consecutive patients for whom telehealth was used in consultations between April and July 2020 were considered for inclusion. The validated Telehealth Usability Questionnaire (TUQ) was used as a model to measure patient acceptance. Overall, 747 patients were observed, of whom 721 agreed to participate (96·5%). The TUQ showed that 86·9% of patients agreed that telehealth was useful; 85·2% supported the interface quality and 81·4% endorsed the interaction quality. Patients aged > 60 y were less likely to agree with the use of telehealth (p < 0·05). A web-based prediction tool was generated to calculate global satisfaction and to identify patients more likely to feel comfortable with telehealth. Telehealth is feasible and allows consultations that are satisfactory for patients. Technological advancements could ease safe implementation of telehealth into everyday practice. Adequate patient selection can be useful to ensure that the ideal strategy is used for each individual during and after the pandemic.

Analysis and Simulation of the Compressive Strength of Bioinspired Lightweight Structures Manufactured by a Stereolithography 3D Printer.

The use of metamaterials is a good alternative when looking for structures that can withstand compression forces without increasing their weight. In this sense, using nature as a reference can be an appropriate option to design this type of material. Therefore, in this work, a comparative study of a selection of eight representative models of a wide variety of existing solutions, both bioinspired and proposed by various researchers, is presented. These models have been manufactured using stereolithography (SLA) printing, which allows complex geometries to be obtained in a simple way that would be more complicated to achieve by other procedures. Additionally, the manufacturing cost of each model has been determined. The compression tests of the different models have made it possible to evaluate the breaking force and its corresponding deformation. Likewise, a finite element analysis of the manufactured models has been carried out to simulate their behavior under compression, achieving results very similar to those obtained in the experimental tests. In this way, it has been concluded that, among the three-dimensional patterns, the structure called "3D auxetic" is the one that supports the greatest breaking force due to the topographic characteristics of its bar structure. Similarly, among the two-dimensional patterns, the structure called "Auxetic 1", with a topography based on curves, is capable of supporting the greatest deformation in the compression direction before breaking. Moreover, the highest resistance-force-to-cost ratio has been obtained with a "3D auxetic" structure.

Clinical mutations in the TERT and TERC genes coding for telomerase components induced oxidative stress, DNA damage at telomeres and cell apoptosis besides decreased telomerase activity.

Telomeres are nucleoprotein structures at the end of chromosomes that maintain their integrity. Mutations in genes coding for proteins involved in telomere protection and elongation produce diseases such as dyskeratosis congenita or idiopathic pulmonary fibrosis known as telomeropathies. These diseases are characterized by premature telomere shortening, increased DNA damage and oxidative stress. Genetic diagnosis of telomeropathy patients has identified mutations in the genes TERT and TERC coding for telomerase components but the functional consequences of many of these mutations still have to be experimentally demonstrated. The activity of twelve TERT and five TERC mutants, five of them identified in Spanish patients, has been analyzed. TERT and TERC mutants were expressed in VA-13 human cells that express low telomerase levels and the activity induced was analyzed. The production of reactive oxygen species, DNA oxidation and TRF2 association at telomeres, DNA damage response and cell apoptosis were determined. Most mutations presented decreased telomerase activity, as compared to wild-type TERT and TERC. In addition, the expression of several TERT and TERC mutants induced oxidative stress, DNA oxidation, DNA damage, decreased recruitment of the shelterin component TRF2 to telomeres and increased apoptosis. These observations might indicate that the increase in DNA damage and oxidative stress observed in cells from telomeropathy patients is dependent on their TERT or TERC mutations. Therefore, analysis of the effect of TERT and TERC mutations of unknown function on DNA damage and oxidative stress could be of great utility to determine the possible pathogenicity of these variants.

The role of psychosis and clozapine load in excessive checking in treatment-resistant schizophrenia: longitudinal observational study.

BACKGROUND: A significant proportion of people with clozapine-treated schizophrenia develop 'checking' compulsions, a phenomenon yet to be understood. AIMS: To use habit formation models developed in cognitive neuroscience to investigate the dynamic interplay between psychosis, clozapine dose and obsessive-compulsive symptoms (OCS). METHOD: Using the anonymised electronic records of a cohort of clozapine-treated patients, including longitudinal assessments of OCS and psychosis, we performed longitudinal multi-level mediation and multi-level moderation analyses to explore associations of psychosis with obsessiveness and excessive checking. Classic bivariate correlation tests were used to assess clozapine load and checking compulsions. The influence of specific genetic variants was tested in a subsample. RESULTS: A total of 196 clozapine-treated individuals and 459 face-to-face assessments were included. We found significant OCS to be common (37.9%), with checking being the most prevalent symptom. In mediation models, psychosis severity mediated checking behaviour indirectly by inducing obsessions (r = 0.07, 95% CI 0.04-0.09; P < 0.001). No direct effect of psychosis on checking was identified (r = -0.28, 95% CI -0.09 to 0.03; P = 0.340). After psychosis remission (n = 65), checking compulsions correlated with both clozapine plasma levels (r = 0.35; P = 0.004) and dose (r = 0.38; P = 0.002). None of the glutamatergic and serotonergic genetic variants were found to moderate the effect of psychosis on obsession and compulsion (SLC6A4, SLC1A1 and HTR2C) survived the multiple comparisons correction. CONCLUSIONS: We elucidated different phases of the complex interplay of psychosis and compulsions, which may inform clinicians' therapeutic decisions.

Surgically treated pelvic liposarcoma and leiomyosarcoma: The effect of tumor size on cancer-specific survival.

INTRODUCTION: In soft tissue pelvic liposarcoma and leiomyosarcoma, it is unknown whether a specific tumor size cut-off may help to better predict prognosis, defined as cancer-specific survival (CSS). We tested whether different tumor size cut-offs, could improve CSS prediction. MATERIALS AND METHODS: Surgically treated non-metastatic soft tissue pelvic sarcoma patients were identified (Surveillance, Epidemiology, and End Results 2004-2019). Kaplan-Meier plots, univariable and multivariable Cox-regression models and receiver operating characteristic-derived area under the curve (AUC) estimates were used. RESULTS: Overall, 672 (65 %) liposarcoma (median tumor size 11 cm, interquartile range [IQR] 7-16) and 367 (35 %) leiomyosarcoma (median tumor size 8 cm, IQR 5-12) patients were identified. The p-value derived ideal tumor size cut-off was 17.1 cm, in liposarcoma and 7.0 cm, in leiomyosarcoma. In liposarcoma, according to p-value derived cut-off, five-year CSS rates were 92 vs 83 % (≤17.1 vs > 17.1 cm). This cut-off represented an independent predictor of CSS and improved prognostic ability from 83.8 to 86.8 % (Δ = 3 %). Similarly, among previously established cut-offs (5 vs 10 vs 15 cm), also 15 cm represented an independent predictor of CSS and improved prognostic ability from 83.8 to 87.0 % (Δ = 3.2 %). In leiomyosarcoma, according to p-value derived cut-off, five-year CSS rates were 86 vs 55 % (≤7.0 vs > 7.0 cm). This cut-off represented an independent predictor of CSS and improved prognostic ability from 68.6 to 76.5 % (Δ = 7.9 %). CONCLUSIONS: In liposarcoma, the p-value derived tumor size cut-off was 17.1 cm vs 7.0 cm, in leiomyosarcoma. In both histologic subtypes, these cut-offs exhibited the optimal statistical characteristics (univariable, multivariable and AUC analyses). In liposarcoma, the 15 cm cut-off represented a valuable alternative.

Prognostic significance of lymph node count in surgically treated patients with T2-4 stage nonmetastatic adrenocortical carcinoma.

PURPOSE: The role of lymphadenectomy and the optimal lymph node count (LNC) cut-off in nonmetastatic adrenocortical carcinoma (nmACC) are unclear. METHODS: Within the Surveillance, Epidemiology, and End Results (SEER) database, surgically treated nmACC patients with T2-4 stages were identified between 2004 and 2020. We tested for cancer-specific mortality (CSM) differences according to pathological N-stage (pN0 vs. pN1) and two previously recommended LNC cut-offs (≥4 vs. ≥5) were tested in pN0 and subsequently in pN1 subgroups in Kaplan-Meier plots and multivariable Cox regression models. RESULTS: Of 710 surgically treated nmACC patients, 185 (26%) underwent lymphadenectomy and were assessable for further analyses based on available LNC data. Of 185 assessable patients, 152 (82%) were pN0 and 33 (18%) were pN1. In Kaplan-Meier analyses, CSM-free survival was 74 vs. 14 months (Δ 60 months, P ≤ 0.001) in pN0 vs. pN1 patients, respectively. In multivariable analyses, pN1 was an independent predictor of higher CSM (HR:3.13, P < 0.001). In sensitivity analyses addressing pN0, LNC cut-off of ≥4 was associated with lower CSM (multivariable hazard ratio [HR]: 0.52; P = 0.002). In sensitivity analyses addressing pN0, no difference was recorded when a LNC cut-off of ≥5 was used (HR:0.60, P = 0.09). In pN1 patients, neither of the cut-offs (≥4 and ≥5) resulted in a statistically significant stratification of CSM rate, and neither reached independent predictor status (all P > 0.05). CONCLUSIONS: Lymphadenectomy provides a prognostic benefit in nmACC patients and identifies pN1 patients with dismal prognosis. Conversely, in pN0 patients, a LNC cut-off ≥4 identifies those with particularly favorable prognosis.

Effectiveness of gamification in nursing degree education.

Background: Previous research in nursing has found favorable results from the use of teaching methodologies alternative to lectures. One of the complementary methodologies used for university teaching is gamification, or the inclusion of game elements, creating a dynamic learning environment that allows the acquisition of knowledge and the development of other skills necessary for nursing students. The purpose of this study was to evaluate the effect of a gamification session on student satisfaction and knowledge scores in nursing students in simulated laboratory practice. Methods: A pre-post quasi-experimental study was conducted with 122 students from the nursing degree program who participated in the research. The evaluation consisted of four sessions of three hours each. In two sessions, participants were trained through a vertical methodology, by means of theoretical training provided by teaching staff, and two hours of clinical simulation, where the students were able to practice the techniques on professional simulators. At the other two sessions, participants received an explanation of the theoretical aspects of the session, one hour of clinical simulation, and one hour of gamification, in which they had to pass tests based on the performance of practical activities on the subject of the session. At the end of the gamification session, all the participants received a certificate as winners of the "nursing game". Results: There was an improvement in the satisfaction and the knowledge level in the gamification sessions. Both were statistically significant (P < 0.001). There was an improvement in the items related to the development of critical thinking and the mobilizing concepts from theory to practice in the gamification sessions. Conclusion: The intervention was effective in improving the satisfaction of the sessions received and in knowledge development.

Multiple Genomic Landscapes of Recombination and Genomic Divergence in Wild Populations of House Mice-The Role of Chromosomal Fusions and Prdm9.

Chromosomal fusions represent one of the most common types of chromosomal rearrangements found in nature. Yet, their role in shaping the genomic landscape of recombination and hence genome evolution remains largely unexplored. Here, we take advantage of wild mice populations with chromosomal fusions to evaluate the effect of this type of structural variant on genomic landscapes of recombination and divergence. To this aim, we combined cytological analysis of meiotic crossovers in primary spermatocytes with inferred analysis of recombination rates based on linkage disequilibrium using single nucleotide polymorphisms. Our results suggest the presence of a combined effect of Robertsonian fusions and Prdm9 allelic background, a gene involved in the formation of meiotic double strand breaks and postzygotic reproductive isolation, in reshaping genomic landscapes of recombination. We detected a chromosomal redistribution of meiotic recombination toward telomeric regions in metacentric chromosomes in mice with Robertsonian fusions when compared to nonfused mice. This repatterning was accompanied by increased levels of crossover interference and reduced levels of estimated recombination rates between populations, together with high levels of genomic divergence. Interestingly, we detected that Prdm9 allelic background was a major determinant of recombination rates at the population level, whereas Robertsonian fusions showed limited effects, restricted to centromeric regions of fused chromosomes. Altogether, our results provide new insights into the effect of Robertsonian fusions and Prdm9 background on meiotic recombination.

The Effects of Online Home-Based Pilates Combined with Diet on Body Composition in Women Affected by Obesity: A Preliminary Study.

Diet and exercise intervention are the first strategies to counteract obesity. An online home-based exercise program may be a feasible approach in an obese population. Therefore, this study aimed to investigate the effects of twelve weeks of online Pilates plus diet on body composition in individuals affected by obesity. Thirty-five females were randomly assigned to a home-based Pilates group (PG, n = 18) or a group without intervention (control group, CG, n = 17). All participants followed a Mediterranean diet. The PG followed a twelve-week online Pilates Matwork program (three times/week; 180 min/week), while the CG was not involved in any structured physical exercise program. Body composition and handgrip strength were evaluated at baseline (T0) and after the intervention (T1). A significant group × time interaction (p < 0.05) was found for the fat mass percentage (pFM). Specifically, the pFM was significantly lower at T1 than at T0 in the PG. Significant group × time interactions for fat-free mass (p < 0.05), appendicular skeletal muscle mass (p < 0.05), and skeletal muscle mass (p < 0.01) were found. All these variables were significantly higher at T1 than at T0 in the PG (p < 0.05). Home-based Pilates combined with diet intervention may represent an effective strategy to improve body composition in terms of fat mass reduction and muscle mass gain in adults affected by obesity.

Impact of Pharmacogenetic Testing on Clozapine Treatment Efficacy in Patients with Treatment-Resistant Schizophrenia.

Managing schizophrenia with clozapine poses a significant challenge due to prevalent therapeutic failures. The increasing interest in personalized medicine underscores the importance of integrating pharmacogenetic information for effective pharmacotherapeutic monitoring in patients. The objective of this study was to explore the correlation between DRD2, HTR2A, SLC6A4, CYP1A2, and ABCB1 polymorphisms and clozapine response in 100 patients with Treatment-Resistant Schizophrenia. Different scales such as the Positive and Negative Syndrome Scale (PANSS), the Warwick-Edinburgh Mental Wellbeing Scale (SWEMWBS), the Global Assessment of Functioning Scale (GAF), the Brief Negative Symptom Scale (BNSS), and pharmacokinetic parameters were used to analyse the efficacy of the treatment. Patients who exclusively responded to clozapine compared to the patients with augmentation strategies exhibited distinctive features, such as lower doses, plasma levels, and presented less-pronounced symptomatology. Genetic associations were explored, highlighting SLC6A4, HTR2A, and the *1F/*1F polymorphism for the CYP1A2 gene.

Updated antimicrobial dosing recommendations for obese patients.

The prevalence of obesity has increased considerably in the last few decades. Pathophysiological changes in obese patients lead to pharmacokinetic (PK) and pharmacodynamic (PD) alterations that can condition the correct exposure to antimicrobials if standard dosages are used. Inadequate dosing in obese patients can lead to toxicity or therapeutic failure. In recent years, additional antimicrobial PK/PD data, extended infusion strategies, and studies in critically ill patients have made it possible to obtain data to provide a better dosage in obese patients. Despite this, it is usually difficult to find information on drug dosing in this population, which is sometimes contradictory. This is a comprehensive review of the dosing of different types of antimicrobials (antibiotics, antifungals, antivirals, and antituberculosis drugs) in obese patients, where the literature on PK and possible dosing strategies in obese adults was critically assessed.

Real-world evidence of tumor and patient characteristics and survival with avelumab maintenance after chemotherapy for advanced and metastatic urothelial carcinoma.

PURPOSE: Despite the prospective randomized controlled JAVELIN Bladder 100 trial, no real-world evidence exists regarding tumor characteristics, adverse events (AE) and survival of avelumab maintenance (AVM) treated patients with partial/complete response or stable disease after previous platinum-based chemotherapy for advanced/metastatic urothelial carcinoma (mUC). METHODS: We relied on our institutional database to identify mUC patients who received AVM between 01/2021-12/2023. The main outcomes consisted of overall (OS) and progression-free survival (PFS) and were computed by Kaplan-Meier estimates. Stratification was performed according to PD-L1 status. RESULTS: Overall, 24 AVM patients were identified at a median age of 71 (interquartile range [IQR]: 67-76) years of which 67% were males. Of these, 63%, 21% and 17% received AVM therapy for bladder cancer and upper tract urothelial carcinoma or both, respectively. PD-L1 status was positive in 45% of patients. During AVM treatment, AEs were observed in 33% of patients, however, were limited to ≤2 grade AEs. At a median follow-up of eight (IQR 4-20) months, 71% of patients had progressed under AVM with median PFS of 6.2 months (CI: 3.2-18.2). Median OS was 13.4 (CI: 6.9-not reached [NR]) months. One-year OS after AVM was 52%. In PD-L1 positive patients, median PFS and OS were 6.4 (CI: 2.7 - NR) months and 13.4 (CI: 7.7 months - NR), respectively. CONCLUSION: AVM is associated with moderate AE rates. Despite similarities in baseline characteristics compared to trial-selected JAVELIN Bladder 100 mUC patients, AVM resulted in longer/similar PFS but significantly shorter OS in in real-world setting.