Recognition and control of neutrophil extracellular trap formation by MICL.

Regulation of neutrophil activation is critical for disease control. Neutrophil extracellular traps (NETs), which are web-like structures composed of DNA and neutrophil-derived proteins, are formed following pro-inflammatory signals; however, if this process is uncontrolled, NETs contribute to disease pathogenesis, exacerbating inflammation and host tissue damage1,2. Here we show that myeloid inhibitory C-type lectin-like (MICL), an inhibitory C-type lectin receptor, directly recognizes DNA in NETs; this interaction is vital to regulate neutrophil activation. Loss or inhibition of MICL functionality leads to uncontrolled NET formation through the ROS-PAD4 pathway and the development of an auto-inflammatory feedback loop. We show that in the context of rheumatoid arthritis, such dysregulation leads to exacerbated pathology in both mouse models and in human patients, where autoantibodies to MICL inhibit key functions of this receptor. Of note, we also detect similarly inhibitory anti-MICL autoantibodies in patients with other diseases linked to aberrant NET formation, including lupus and severe COVID-19. By contrast, dysregulation of NET release is protective during systemic infection with the fungal pathogen Aspergillus fumigatus. Together, we show that the recognition of NETs by MICL represents a fundamental autoregulatory pathway that controls neutrophil activity and NET formation.

Understanding inhibitory receptor function in neutrophils through the lens of CLEC12A.

Neutrophils are the first leukocytes recruited from the circulation in response to invading pathogens or injured cells. To eradicate pathogens and contribute to tissue repair, recruited neutrophils generate and release a host of toxic chemicals that can also damage normal cells. To avoid collateral damage leading to tissue injury and organ dysfunction, molecular mechanisms evolved that tightly control neutrophil response threshold to activating signals, the strength and location of the response, and the timing of response termination. One mechanism of response control is interruption of activating intracellular signaling pathways by the 20 inhibitory receptors expressed by neutrophils. The two inhibitory C-type lectin receptors expressed by neutrophils, CLEC12A and DCIR, exhibit both common and distinct molecular and functional mechanisms, and they are associated with different diseases. In this review, we use studies on CLEC12A as a model of inhibitory receptor regulation of neutrophil function and participation in disease. Understanding the molecular mechanisms leading to inhibitory receptor specificity offers the possibility of using physiologic control of neutrophil functions as a pharmacologic tool to control inflammatory diseases.

Integrative tissue, cellular and molecular responsiveness of an innovative ex vivo model of the Staphylococcus aureus-mediated bone infection.

Osteomyelitis is a pathological condition of the bone, frequently associated with the presence of infectious agents - namely Staphylococcus aureus - that induce inflammation and tissue destruction. Recent advances in the understanding of its pathophysiology and the identification of innovative therapeutic approaches were gathered from experimental in vitro and in vivo systems. However, cell culture models offer limited representativeness of the cellular functionality and the cell-cell and cell-matrix interactions, further failing to mimic the three-dimensional tissue organization; and animal models allow for limited mechanistic assessment given the complex nature of systemic and paracrine regulatory systems and are endorsed with ethical constraints. Accordingly, this study aims at the establishment and assessment of a new ex vivo bone infection model, upon the organotypic culture of embryonic chicken femurs colonized with S. aureus, highlighting the model responsiveness at the molecular, cellular, and tissue levels. Upon infection with distinct bacterial inoculums, data reported an initial exponential bacterial growth, followed by diminished metabolic activity. At the tissue level, evidence of S. aureus-mediated tissue destruction was attained and demonstrated through distinct methodologies, conjoined with decreased osteoblastic/osteogenic and increased osteoclastic/osteoclastogenic functionalities-representative of the osteomyelitis clinical course. Overall, the establishment and characterization of an innovative bone tissue infection model that is simple, reproducible, easily manipulated, cost-effective, and simulates many features of human osteomyelitis, further allowing the maintenance of the bone tissue's three-dimensional morphology and cellular arrangement, was achieved. Model responsiveness was further demonstrated, showcasing the capability to improve the research pipeline in bone tissue infection-related research.

Call to action: Harmonization of pharmacovigilance regulations for post-marketing pregnancy and breastfeeding safety studies.

Globally, more than 200 million women become pregnant each year, most of whom receive medications despite limited information on their safe use during pregnancy. The paucity of drug safety data on pregnant and breastfeeding women stems from the routine exclusion of this population from clinical trials due to scientific, ethical, regulatory and legal concerns. Consequently, at the time of initial drug approval, there may be scant safety data to inform the drug benefit-risk balance to the mother, foetus or infant. Although momentum is growing to include this underrepresented population in clinical trials, most information on drug exposure outcomes comes from data collected in the postmarketing setting. Regulatory guidance and legislation on medication use in pregnancy and breastfeeding were reviewed globally by the TransCelerate IGR PV Pregnancy and Breastfeeding Team. The International Conference of Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) standards and Council for International Organizations of Medical Sciences guidelines served as benchmarks for national safety regulations and guidance. The landscape assessment identified a lack of harmonization of global regulations on research in pregnant and breastfeeding women and a lack of specific regulations on this topic in the majority of the territories included in the assessment. This article focuses on the ambiguities and lack of harmonization in global regulations on postmarketing pregnancy and breastfeeding safety studies. There is currently no ICH standard to guide these types of safety studies and, in most regions reviewed, there are no clear regulations or guidance on when and how to conduct them. While a challenging undertaking, greater clarity and harmonization would facilitate more timely completion of postmarketing pregnancy safety studies that would ultimately generate the critical data needed to optimize benefit-risk decisions for women who may conceive, as well as pregnant and breastfeeding women.

Effect of galcanezumab in women with episodic migraine meeting criteria for menstrually related migraine: A post hoc analysis of EVOLVE-1 and EVOLVE-2.

BACKGROUND: We evaluated galcanezumab for migraine prevention in patients who met International Classification of Headache Disorders, 3rd edition criteria for menstrually related migraine (MRM). METHODS: Patients were identified post hoc from three double-blind, randomized, phase 3 clinical trials in patients with episodic migraine. Patients completed a 1-month prospective baseline period and up to 6 months (EVOLVE-1 and -2, studies pooled) of double-blind treatment with galcanezumab (120 mg/month) or placebo. Menses and headache information were recorded by electronic daily diary. Patients with a migraine attack starting during the 5-day perimenstrual interval (first day of bleeding ± 2 days) for ≥2 of their first three diary-recorded menstrual cycles were categorized as having MRM. The primary efficacy measure was mean change in monthly migraine headache days from baseline, averaged over Months 4 through 6. Response rates, change in monthly perimenstrual migraine headache days, monthly non-perimenstrual migraine headache days, and quality of life were also assessed. RESULTS: Post hoc MRM analysis criteria were met by 462/1133 women (41%). Mean (standard deviation) baseline monthly migraine headache days were 9.7 (±3.1; n = 146) for galcanezumab-treated patients and 9.6 (±2.8; n = 316) for placebo-treated patients. The mean change (standard error [SE]) in migraine headache days over Months 4 through 6 was -5.1 days (±0.39) for galcanezumab versus -3.2 (±0.35) for placebo (p < 0.001). The mean change (SE) in perimenstrual migraine headache days over Months 4 through 6 was -0.75 days (±0.08) for galcanezumab versus -0.49 (±0.07) for placebo (p = 0.004). For migraine headache days outside the perimenstrual period, the mean change in migraine headache days was -4.6 (±0.38) for galcanezumab and -2.8 (±0.33) for placebo (p < 0.001). Improvements in response rates and the Migraine-Specific Quality of Life Questionnaire were also observed over Months 4 through 6. CONCLUSION: Galcanezumab was effective for migraine prevention in women with MRM.

Mucoadhesive delivery systems for oral candidiasis treatment: A systematic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis aimed to evaluate the clinical and mycological effectiveness of mucoadhesives as vehicles for drugs or natural products in the treatment of oral candidiasis. MATERIALS AND METHODS: The search for articles was carried out in the Medline/PubMed, SCOPUS, EMBASE, Web of Science, Cochrane Library, and SciELO databases before August 2023. We selected the studies, extracted the data, evaluated the study quality, graded the evidence, performed the risk of bias, and carried out meta-analysis. RESULTS: A total of 389 potentially relevant articles were identified, and 11 studies (1869 participants) met the inclusion criteria of the systematic review. The overall risk of bias was considered low. The most common presentation of mucoadhesives was tablets, with miconazole being the most frequently drug used in the delivery system. Mucoadhesives demonstrated comparable efficacy with topical or systemic antifungal agents, with no significant differences between treatments in terms of clinical (RR = 0.907; 95CI = 0.3-1.297; p = 0.591; I2 = 64.648) or mycological (RR = 0.95; 95CI = 0.667-1.360; p = 0.789; I2 = 73.271) efficacy. CONCLUSIONS: Mucoadhesives may be a suitable alternative to conventional treatments, with the advantage of reducing the frequency of application by up to 5 times and the daily dosage by up to 20 times.

Role of MTHFR, IRF6, PAX7 and TP63 SNPs in susceptibility to non-syndromic orofacial cleft, a candidate gene study in a Portuguese population.

BACKGROUND: Non-syndromic orofacial cleft (NSOC) is a complex phenotype, involving multiple genetic and environmental factors. Association studies exploring the genetic susceptibility to this prevalent oral malformation show variability of results in different populations. Using a candidate gene approach, we aimed to verify the role of four single-nucleotide polymorphisms (SNPs) in the susceptibility to NSOC in Portuguese patients. METHODS: A total of 254 non-consanguineous individuals of Portuguese were recruited, including 120 patients with NSOC and 134 controls. About 92% of these patients had non-syndromic cleft lip with or without cleft palate (NSCL/P) and 8% had only non-syndromic cleft palate (NSCP). SNPs in the MTHFR (rs1801133), IRF6 (rs642961), PAX7 (rs742071) and TP63 (rs9332461) genes were studied, using a real-time approach with TaqMan probes. Allelic, genotypic, dominant, recessive and over-dominant models were explored using a chi-squared test. Adjusted p-value was calculated for multiple comparisons using the Benjamini-Hochberg false discovery rate (FDR). RESULTS: All SNPs were in Hardy-Weinberg equilibrium. For MTHFR, IRF6, and PAX7 SNPs, no statistically significant difference was highlighted for any of the evaluated models. For TP63 SNP, data fitted an over-dominant model, with a protective effect for heterozygotes (OR 1.897; CI 95% [1.144-3.147]; p < .016, when comparing controls vs. cases), but significance was lost when applying adjusted p-value for multiple comparisons (4 × 5 tests). CONCLUSION: In this Portuguese population, there was no evidence of an association between the evaluated SNPs and NSOC. For TP63 SNP, the possibility of a protective effect of heterozygotes should be further investigated.

The Effect of Dexlansoprazole on Gastroesophageal Reflux Disease: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis evaluated the efficacy of dexlansoprazole (a proton pump inhibitor-PPI) in resolving heartburn, reflux, and other symptoms and complications resulting from gastroesophageal reflux disease (GERD). The study followed PRISMA 2020 and was registered in PROSPERO (CRD42020206513). The search strategy used MeSH and free terms appropriately adapted for each database. Only randomized clinical trials (RCTs) were included. The Cochrane tool (RoB 2.0) was used to assess the risk of bias, and the certainty of evidence was rated using GRADE. Ten RCTs were included. Dexlansoprazole outperformed the placebo and other PPIs in the resolution of heartburn and reflux symptoms in patients with GERD, with benefits during and after treatment, especially in those with moderate and severe symptoms. The meta-analyses indicated that dexlansoprazole at doses of 30 and 60 mg had more 24 h heartburn-free days and nights compared to the placebo medications; no difference was reported between dexlansoprazole at doses of 30 and 60 mg in heartburn-free nights. A low bias risk and a moderate certainty of evidence were observed. This review confirms the therapeutic effect of dexlansoprazole (placebo-controlled) and its improvements in GERD symptoms compared to another PPI. However, the interpretation of the results should be carried out cautiously due to the small number of included studies and other reported limitations.

Evaluation of lidocaine administration into the ovarian pedicle for the control of intraoperative and early postoperative pain during ovariohysterectomy in dogs.

OBJECTIVE: To evaluate effects of lidocaine 2% administration into the ovarian pedicle on intraoperative nociception and early postoperative pain in dogs undergoing ovariohysterectomy. STUDY DESIGN: Prospective, randomized, blinded clinical study. ANIMALS: A total of 20 healthy adult female dogs of different breeds. METHODS: Dogs were premedicated with acepromazine (0.02 mg kg-1) and morphine (0.5 mg kg-1) intramuscularly, anesthesia induced with propofol and maintained with isoflurane. Dogs were randomly assigned to be administered 2 mL of saline (group S) or lidocaine 2% (group L) into the mesovarium (1 mL each side). Heart rate (HR) and noninvasive systemic arterial pressure were recorded before surgery (T0), before (T1) and during ligation of the right ovarian pedicle (T2), before (T3) and during ligation of the left ovarian pedicle (T4). Rescue treatment (propofol) was administered if HR or systolic arterial pressure (SAP) increased by 20% compared with the previous time point. Pain, assessed with the Glasgow Composite Measure Pain Scale-Short Form (CMPS-SF) was recorded before premedication (baseline) and after extubation. Administration of postoperative rescue analgesia was recorded. RESULTS: In group S, HR was higher at T2 than T1 (112 ± 18 versus 89 ± 21 beats minute-1, p = 0.001) There were no significant differences between treatments at any time. SAP was higher at T2 than T1 in group S (110 ± 12 versus 100 ± 10 mmHg, p = 0.031). SAP was higher in group S than group L at T3 (113 ± 12 and 91 ± 10 mmHg, respectively, p = 0.001). No dogs required propofol intraoperatively. All dogs required postoperative rescue analgesia. Compared with baseline, CMPS-SF increased 60 minutes after extubation (group S; p = 0.019, group L; p = 0.043). CONCLUSIONS AND CLINICAL RELEVANCE: Administration of lidocaine 2% into the mesovarium did not reduce intraoperative nociception and did not improve postoperative analgesia.

The effectiveness of mindfulness for the management of anxiety in the nursing staff: Systematic review and meta-analysis.

A systematic review with meta-analysis following Joanna Briggs Institute recommendations. It aimed to determine the effectiveness of mindfulness for the management of anxiety symptoms in the nursing staff and stress as a secondary outcome. The databases searched were MEDLINE, Embase, LILACS, CINAHL, Web of Science, Scopus and Psycinfo. Search was conducted in October 2022. Independent reviewers used standardized methods to research, track, and code the included studies. Data meta-analysis was performed using random effects models. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was used as an approach to assess the quality and certainty of evidence in research studies. The review examined the effectiveness of mindfulness on nursing staff in 13 studies. The meta-analysis revealed a statistically significant decrease in anxiety and stress after treatment, with an average reduction of 0.36 in anxiety and 0.48 in stress. The results emphasizes the possibility of mindfulness being an effective intervention to the management of anxiety and stress in nursing staff. However, the studies analyzed presented limitations in the design and sampling in the development of the intervention, which impact the conclusive statements about the effectiveness of mindfulness and the generalization of the results. The implications to the nursing field involve adopting evidence-based research and practices to improve the well-being and quality of life of nursing professionals, as well as strengthening the evidence base surrounding mindfulness interventions in nursing practice. This may lead to changes in healthcare policies, care practices, and recognition of the importance of nurses' well-being for effective healthcare delivery.

Retinoic acid induces the osteogenic differentiation of cat adipose tissue-derived stromal cells from distinct anatomical sites.

Mesenchymal stromal cells-based regenerative orthopedic therapies have been used in cats as a promising and innovative therapeutic approach to enhance the repair of bone defects. Adipose tissue-derived stromal cells (ADSCs) can be obtained from two main sites-subcutaneous and visceral-with established differences regarding structure, composition, cell content, and functionality. However, in cats, to the best of the authors' knowledge, no studies have been conducted to compare the functional activity of the ADSCs isolated from the two sites, and the impact of these differences on the induced osteogenic potential. Additionally, retinoic acid has been recently regarded as a new osteogenic inducer within cells of distinct species, with undisclosed functionality on cat-derived cell populations. Thus, the present study aimed to evaluate the functional activity of ADSCs isolated from the subcutaneous and visceral adipose sites (SCAT and VAT, respectively) of the cat, as well as the effects of two osteogenic-inducing conditions-the classic dexamethasone, ß-glycerophosphate and ascorbic acid-supplemented media (Dex + ß + AAM), and Retinoic Acid-supplemented media (RAM). The adipose tissue of subcutaneous and visceral origin was isolated, characterized, and ADSCs were isolated and grown in the presence of the two osteogenic-inducing conditions, and characterized in terms of proliferation, metabolic activity, morphology, and osteogenic activity. Our results demonstrated a distinct biological profile of the two adipose tissue sites regarding cell size, vascularization, and morphology. Further, osteogenic-induced ADSCs from both sites presented an increased expression of alkaline phosphatase activity (ALP) and cytochemical staining, as compared with control. Overall, RAM induced higher levels of ALP activity than Dex + ß + AAM, supporting an increased osteogenic activation. Additionally, VAT was the tissue with the best osteogenic potential, showing higher levels of ALP expression, particularly with RAM. In conclusion, different characteristics were found between the two adipose tissue sites-SCAT and VAT, which probably reflect the differences found in the functionality of isolated ADSCs from both tissues. Furthermore, for cat, VAT shows a greater osteogenic-inductive capacity than SCAT, particularly with RAM, which can be of therapeutic relevance for regenerative medicine applications.

Repurposing sarecycline for osteoinductive therapies: an in vitro and ex vivo assessment.

INTRODUCTION: Tetracyclines (TCs) embrace a class of broad-spectrum antibiotics with unrelated effects at sub-antimicrobial levels, including an effective anti-inflammatory activity and stimulation of osteogenesis, allowing their repurposing for different clinical applications. Recently, sarecycline (SA)-a new-generation molecule with a narrower antimicrobial spectrum-was clinically approved due to its anti-inflammatory profile and reduced adverse effects verified with prolonged use. Notwithstanding, little is known about its osteogenic potential, previously verified for early generation TCs. MATERIALS AND METHODS: Accordingly, the present study is focused on the assessment of the response of human bone marrow-derived mesenchymal stromal cells (hBMSCs) to a concentration range of SA, addressing the metabolic activity, morphology and osteoblastic differentiation capability, further detailing the modulation of Wnt, Hedgehog, and Notch signaling pathways. In addition, an ex vivo organotypic bone development system was established in the presence of SA and characterized by microtomographic and histochemical analysis. RESULTS: hBMSCs cultured with SA presented a significantly increased metabolic activity compared to control, with an indistinguishable cell morphology. Moreover, RUNX2 expression was upregulated 2.5-fold, and ALP expression was increased around sevenfold in the presence of SA. Further, GLI2 expression was significantly upregulated, while HEY1 and HNF1A were downregulated, substantiating Hedgehog and Notch signaling pathways' modulation. The ex vivo model developed in the presence of SA presented a significantly enhanced collagen deposition, extended migration areas of osteogenesis, and an increased bone mineral content, substantiating an increased osteogenic development. CONCLUSION: Summarizing, SA is a promising candidate for drug repurposing within therapies envisaging the enhancement of bone healing/regeneration.

Circular RNAs: Promising Targets in Osteoporosis.

PURPOSE OF REVIEW: Circular RNAs (circRNAs) are RNA transcripts derived from fragments of pre-messenger RNAs through a back-splicing process. An advantage that rises from their circular covalently closed conformation is their high stability, when compared with their linear counterparts. The current review focuses on the emerging roles of circRNAs in osteoporosis, including in osteogenic differentiation and osteoclastogenesis. Their potential as osteoporosis biomarkers will also be discussed. RECENT FINDINGS: Although firstly described as non-coding, some of these single-stranded RNAs were recently reported to possess protein-coding capacity. On the other hand, the circRNAs exhibit cell and tissue-specific patterns at the transcriptome level in eukaryotes and are regulated throughout the development or disease progression. Even though thousands of these circular transcripts are listed and annotated, only a limited number of studies describe their biological role in bone processes. Recent evidence indicates inhibitory activator roles in both osteoblasts and osteoclasts differentiation and function. Latest screenings in the blood, plasma, or serum of osteoporosis patients support the potential for circRNA signature to be used as biomarkers in osteoporosis, but further validation is required. While intense research into circRNAs has been detailing their biological roles, there remains a need for standardization and further research to fulfil the future potential of this emerging and highly promising class of regulatory molecules.

Structural modification of naturally occurring phenolics as a strategy for developing cytotoxic molecules towards cancer cells.

Natural products belonging to different chemical classes have been established as a promising source of novel anticancer drugs. Several low-molecular-weight compounds from the classes of monoterpenes, phenylpropanoids, and flavonoids were shown to possess anticancer activities in previous studies. In this work, over 20 semisynthetic derivatives of molecules belonging to these classes, namely thymol, eugenol, and 6-hydroxyflavanone were synthesized and tested for their cytotoxicity against two human cancer cell lines, namely AGS cells (gastric adenocarcinoma) and A549 cells (human lung carcinoma). An initial screening based on viability assessment was performed to identify the most cytotoxic compounds at 100 µM. The results evidenced that two 6-hydroxyflavanone derivatives were the most cytotoxic among the compounds tested, being selected for further studies. These derivatives displayed enhanced toxicity when compared with their natural counterparts. Moreover, the lactate dehydrogenase (LDH) assay showed that the loss of cell viability was not accompanied by a loss of membrane integrity, thus ruling out a necrotic process. Morphological studies with AGS cells demonstrated chromatin condensation compatible with apoptosis, confirmed by the activation of caspase 3/7. Furthermore, a viability assay on a noncancer human embryonic lung fibroblast cell line (MRC-5) confirmed that these two derivatives possess selective anticancer activity.

Microgap and bacterial microleakage during the osseointegration period: An in vitro assessment of the cover screw and healing abutment in a platform-switched implant system.

STATEMENT OF PROBLEM: Microgap and bacterial microleakage at the implant-prosthetic abutment interface are recognized concerns for implant-supported restorations, leading to inflammation of the peri-implant tissues, with deleterious consequences for crestal bone levels. However, little is known regarding the interface established between the implant and the healing abutment or cover screw placed for the osseointegration phase. PURPOSE: The purpose of this in vitro study was to characterize the implant-cover screw and implant-healing abutment interfaces of a platform-switched implant system to determine the microgap and bacterial microleakage of the system and evaluate the biological response and functionality of an interface sealing agent. MATERIAL AND METHODS: The interfacial microgaps of the implant-healing abutment and implant-cover screw interfaces were characterized by scanning electron microscopy (n=10), and bacterial microleakage was evaluated after colonization with Enterococcus faecalis in a 30-day follow-up (n=10). The sealing efficacy and irritation potential of a silicone-based sealer were determined by using the hen's egg test on chorioallantoic membrane assay. The 2-sample t test was performed to compare means between groups, and data presented with the Kaplan-Meier method were compared statistically by using the log-rank test (α=.05). RESULTS: The interfacial microgap was less than 2.5 µm for both systems. Bacterial microleakage was noted in approximately 50% of the specimens, particularly at early time points, at both the healing abutment and cover screw interfaces. The silicone-based sealer prevented bacterial leakage in the experimental setting. CONCLUSIONS: The implant-healing abutment and implant-cover screw interfaces of the tested system, despite the low microgap, allowed for bacterial microleakage after internal colonization. The use of a nonirritating silicone-based sealing agent effectively sealed the system.

Barriers and Facilitators to Integrating Depression Treatment Within a TB Program and Primary Care in Brazil.

Tuberculosis (TB) and depression is common and is associated with poor TB outcomes. The World Health Organization End TB Strategy explicitly calls for the integration of TB and mental health services. Interpersonal Counseling (IPC) is a brief evidence-based treatment for depression that can be delivered by non-mental health specialists with expert supervision. The goal of this study was to explore potential barriers and facilitators to training non-specialist providers to deliver IPC within the TB Control Program and primary care in Itaboraí, Rio de Janeiro state. Data collection consisted of six focus groups (n = 42) with health professionals (n = 29), program coordinators (n = 7), and persons with TB (n = 6). We used open coding to analyze the data, followed by deductive coding using the Chaudoir multi-level framework for implementation outcomes. The main structural barriers identified were poverty, limited access to treatment, political instability, violence, and social stigma. Organizational barriers included an overburdened and under-resourced health system with high staff turnover. Despite high levels of stress and burnout among health professionals, several provider-level facilitators emerged including a high receptivity to, and demand for, mental health training; strong community relationships through the community health workers; and overall acceptance of IPC delivered by any type of health provider. Patients were also receptive to IPC being delivered by any type of professional. No intervention-specific barriers or facilitators were identified. Despite many challenges, integrating depression treatment into primary care in Itaboraí using IPC was perceived as acceptable, feasible, and desirable.

The development of interprofessional education and collaborative practice in Latin America and the Caribbean: preliminary observations.

The Pan-American Health Organization (PAHO) and World Health Organization have encouraged countries across Latin America and the Caribbean (LAC) to incorporate interprofessional education and collaborative practice (IPECP) into policies on the health workforce, and support policymakers in expanding its use. PAHO recommend countries to promote the development of interprofessional teams in integrated health services networks using IPECP. The creation of the Regional Network for Interprofessional Education in the Americas, the mobilization of a series of IPECP regional meetings, and the development of national IPECP action plans are the most promising results achieved thus far. This report describes the process of implementing IPECP in LAC countries as an innovative initiative in interprofessional health policy.

The student experience during a rural clerkship in Brazil.

INTRODUCTION: Universities have the ability to bring science and comprehensive care to remote regions. This can be done through the creation of rural clerkships during the training of health professionals. METHODS: Report of students' experiences during their rural clerkships in Brazil. RESULTS: Rural clerkships made contact possible between students from different areas of health, such as medicine, nutrition, psychology, social assistance, and nursing. This multidisciplinary team expanded the possibilities of care in the region, which often suffers from a shortage of healthcare professionals. DISCUSSION: Students noticed that the use of management and treatment guided by evidence-based medicine was more common in their university than in rural facilities. The relationship between students and local health professionals provided discussions and application of new scientific evidence and updates. Due to the greater number of students and residents of the multi-professional health team, it was possible to initiate health education, integrated case discussions, and territorialization projects. Areas with untreated sewage and a high local concentration of scorpions were identified, which allowed a targeted intervention. The students noticed the numerous differences between the tertiary care they were used to at medical school and the access to health and resources in a rural area. Collaboration between educational institutions and rural areas with scarce resources makes it possible to exchange knowledge between students and local professionals. In addition, these rural clerkships expand the possibilities for care for local patients and make it possible to carry out projects related to health education.

EGFR Mutations and PD-L1 Expression in Early-Stage Non-Small Cell Lung Cancer: A Real-World Data From a Single Center in Brazil.

BACKGROUND: Targeted and immunotherapies are currently moving toward early-stage settings for patients with non-small cell lung cancer (NSCLC). Predictive biomarkers data are scarce in this scenario. We aimed to describe the frequency of EGFR mutations and PD-L1 expression levels in early-stage non-squamous patients with NSCLC from a large, single Brazilian oncology center. METHODS: We retrospectively evaluated patients with NSCLC diagnosed at an early-stage (IB to IIIA-AJCC seventh edition) at Barretos Cancer Hospital (n = 302). EGFR mutational status was assessed in FFPE tumor tissues using distinct methodologies (NGS, Cobas, or Sanger sequencing). PD-L1 expression was evaluated by immunohistochemistry (clone 22C3) and reported as Tumor Proportion Score (TPS), categorized as <1%, 1-49%, and ≥50%. We evaluated the association between EGFR mutational status and PD-L1 expression with sociodemographic and clinicopathological parameters by Fisher's test, qui-square test, and logistic regression. Survival analysis was assessed by the Kaplan-Meier method and Cox regression model. RESULTS: EGFR mutations were detected in 17.3% (n = 48) of cases and were associated with female sex, never smokers, and longer overall and event-free survival. PD-L1 positivity was observed in 36.7% (n = 69) of cases [TPS 1-49% n = 44(23.4%); TPS ≥50% n = 25(13.3%)]. PD-L1 positivity was associated with smoking, weight loss, and higher disease stages (IIB/IIIA). CONCLUSION: The frequencies of EGFR mutations and PD-L1 positivity were described for early-stage non-squamous patients with NSCLC. These results will be essential for guiding treatment strategies with the recent approvals of osimertinib and immunotherapy in the adjuvant setting.

CT of Ovarian Cancer for Primary Treatment Planning: What the Surgeon Needs to Know-Radiology In Training.

A 60-year-old woman presented with intermittent abdominal pain, an elevated serum CA-125 level, and an abnormal CT examination and was ultimately diagnosed with advanced-stage high-grade serous ovarian cancer. Key tumor locations on CT scans that should be highlighted by the radiologist to guide treatment selection are discussed.