Beyond the mouth: Uncovering non-secretory multiple myeloma through oral symptoms.

Non-secretory multiple myeloma (NSMM) is a rare cancer of plasma cells characterized by the absence of detectable monoclonal M protein in the blood or urine. A 57-year-old woman presented with mandibular pain but without intraoral swelling. Imaging studies revealed multiple osteolytic lesions in her mandible and pronounced root resorption of the left mandibular second molar. Biopsy results showed atypical plasmacytoid cells positive for anti-kappa, CD138, MUM1, and CD79a antibodies, but negative for anti-lambda and CD20. These results were indicative of a malignant plasma cell neoplasm. No abnormalities were revealed by free light chain assay or by serum or urine protein electrophoresis, leading to a diagnosis of NSMM. The patient began chemotherapy in conjunction with bisphosphonate therapy and achieved remission following treatment. This case underscores the critical role of dentists in the early detection and prevention of NSMM complications, as the disease can initially present in the oral cavity.

Intrathecal dexamethasone as an adjuvant for spinal anesthesia: a systematic review.

INTRODUCTION: Spinal anesthesia is a common anesthetic technique for lower limb and abdominal surgery. Despite its efficacy, its use is limited because of its duration and potential severe side effects, especially in high-risk patients undergoing major surgery. Adjuvants such as dexamethasone offer the potential to prolong the anesthetic effect and reduce the need for local anesthetics while reducing the incidence of serious adverse events. The purpose of this systematic review is to evaluate the efficacy of dexamethasone as an intrathecal adjuvant in prolonging anesthetic duration, delaying pain onset, and minimizing adverse events (PROSPERO registration: CRD42022350218). EVIDENCE ACQUISITION: We included randomized controlled trials conducted in adult patients undergoing spinal anesthesia for lower limb or abdominal surgery and comparing the performance of dexamethasone with alternative spinal treatments. A comprehensive systematic search was conducted on PubMed/MEDLINE, Scopus, CINAHL, EMBASE, CENTRAL, and Cochrane Library from February to June 2023 without language restriction. Risk of bias was assessed using the Cochrane Risk of Bias Tool (RoB2). EVIDENCE SYNTHESIS: Ten studies, nine of which were at high risk of bias, were included (N.=685 patients). Overall, intrathecal dexamethasone was associated with a longer duration of sensory block, improvement in the duration or extent of postoperative analgesia, and significant shortening of block onset. The role of dexamethasone in prolonging motor block was not clear. The incidence of adverse events was low. Intrathecal dexamethasone has been shown to be a potentially valuable adjuvant to prolong the duration of sensory block and improve postoperative analgesia without increasing adverse events. CONCLUSIONS: Given the wide heterogeneity of methodological approaches, further investigation is needed. Considering the limitations of the included studies and awaiting more conclusive evidence, the prudent use of dexamethasone could be recommended in those specific situations where general anesthesia or higher local anesthetics should be avoided.

Mapping trends in preemptive analgesia related to oral surgery with the use of Ibuprofen: a comprehensive quantitative and qualitative analysis of bibliometric parameters.

PURPOSE: This study aims to conduct a thorough analysis, both quantitative and qualitative, of bibliometric parameters related to preemptive analgesia (PA) in oral surgical procedures (OSP). METHODS: Research trends on PA in OSP using ibuprofen were reviewed through bibliometric analysis of 68 journal articles published from 1991 to 2022 in the Web of Science database. Bibliometric indicators were applied to analyze the journal article data, including the annual distribution of publications and literature growth, document types, citation indicators to measure qualitative research performance, and keyword mapping to identify research trends. The results were imported into RStudio, and the Bibliometrix package was used to prepare and analyze the metadata. RESULTS: The 68 included articles received a total of 900 citations, ranging from 1 source to 72 citations with some fluctuations. The papers on PA in OSP using ibuprofen had an average of 16.85 citations per paper. These publications were originated from 25 countries, with the highest contributions from Brazil (n = 17), the USA (n = 13), and Turkey (n = 8). The top five major contributing journals were the International Journal of Oral and Maxillofacial Surgery, Journal of Oral and Maxillofacial Surgery, Journal of Cranio-Maxillo-Facial Surgery, Journal of Periodontology, and Acta Odontologica Scandinavica, representing more than half of all selected papers. CONCLUSION: Papers focused on PA in OSP received numerous citations. The citation per article correlated with the number of publications at the affiliation, author, country, and journal levels. However, there is still a scarcity of studies in this field.

Rectus sheath block added to parasternal block may improve postoperative pain control and respiratory performance after cardiac surgery: a superiority single-blinded randomized controlled clinical trial.

BACKGROUND: The population undergoing cardiac surgery confronts challenges from uncontrolled post-sternotomy pain, with possible adverse effects on outcome. While the parasternal block can improve analgesia, its coverage may be insufficient to cover epigastric area. In this non-blinded randomized controlled study, we evaluated the analgesic and respiratory effect of adding a rectus sheath block to a parasternal block. METHODS: 58 patients undergoing cardiac surgery via median sternotomy were randomly assigned to receive parasternal block with rectus sheath block (experimental) or parasternal block with epigastric exit sites of chest drains receiving surgical infiltration of local anesthetic (control). The primary outcome of this study was pain at rest at extubation. We also assessed pain scores at rest and during respiratory exercises, opiate consumption and respiratory performance during the first 24 hours after extubation. RESULTS: The median (IQR) maximum pain scores (on a 0-10 Numeric Rate Scale (NRS)) at extubation were 4 (4, 4) in the rectus sheath group and 5 (4, 5) in the control group (difference 1, p value=0.03). Rectus sheath block reduced opioid utilization by 2 mg over 24 hours (IC 95% 0.0 to 2.0; p<0.01), reduced NRS scores at other time points, and improved respiratory performance at 6, 12, and 24 hours after extubation. CONCLUSION: The addition of a rectus sheath block with a parasternal block improves analgesia for cardiac surgery requiring chest drains emerging in the epigastric area. TRIAL REGISTRATION NUMBER: NCT05764616.

Central venous accesses in prone position during the pandemic period: A narrative review.

The unprecedented challenges posed by the global COVID-19 pandemic have magnified the significance of managing intensive care patients in prone positions, particularly those requiring mechanical ventilation. Central venous access is crucial for delivering essential therapies to patients, particularly in intensive care settings. However, the shift in patient management during the pandemic, necessitating prone positioning for improved oxygenation, presented unique hurdles in maintaining and establishing central venous access. Before the pandemic, scant literature detailed the insertion of vascular access devices in prone or unconventional positions. Limited case reports and letters highlighted the feasibility of procedures like ultrasound-guided central catheter placement in patients undergoing surgery or with specific clinical needs. During the pandemic, a surge in case reports and series illuminated the complexities faced by clinicians in maintaining vascular access during pronation procedures. These reports delineated critical scenarios, ranging from rapid clinical deterioration necessitating immediate interventions to challenges with vascular access device (VAD) malfunctions or misplacements during prone maneuvers. Patient selection and device types emerged as critical considerations. Various scenarios, including patients transitioning to prone position from non-invasive ventilation and those requiring additional access for therapies like dialysis, posed challenges in device selection and placement. Successful VAD insertion techniques in prone patients encompassed multiple anatomical sites, including the internal jugular, brachial, femoral, and popliteal veins. However, challenges persisted, particularly with respect to anatomical variations and technical complexities in cannulation. Further research, standardized protocols, and randomized studies are needed to refine and validate the proposed strategies in both pandemic and non-pandemic settings.

Lateral Femoral Cutaneous Nerve Block or Wound Infiltration Combined with Pericapsular Nerve Group (PENG) Block for Postoperative Analgesia following Total Hip Arthroplasty through Posterior Approach: A Randomized Controlled Trial.

Background: Pericapsular nerve group (PENG) block, although effective for pain management following total hip arthroplasty (THA), does not cover skin analgesia. In this randomized controlled trial, we compared the effectiveness of PENG block combined with lateral femoral cutaneous nerve (LFCN) block or wound infiltration (WI) on postoperative analgesia and functional outcomes. Methods: Fifty patients undergoing posterior-approached THA under spinal anesthesia were randomly allocated to receive LFCN block with 10 mL of 0.5% ropivacaine or WI with 20 mL of 0.5% ropivacaine. In both groups, PENG block was performed by injecting 20 mL of 0.5% ropivacaine. Primary outcomes were static and dynamic pain scores (0-10 numeric rating scale) measured in the first 24 h after surgery. Secondary outcomes included postoperative opioid consumption, functional assessment and length of hospital stay. Results: Postoperative static NRS of patients receiving LFCN was higher than that of patients receiving WI at 6 h but lower at 24 h, with a median (IQR) of 3 (2-4) vs. 2 (1-2) (p < 0.001) and 2 (2-3) vs. 3 (3-4) (p = 0.02), respectively. Static pain scores at 12 h did not show significant differences, with an NRS of 3 (2-4) for WI vs. 3 (3-4) for LFCN (p = 0.94). Dynamic pain and range of movement followed a similar trend. No significant differences were detected in other outcomes. Conclusions: LFCN block was not inferior to WI for postoperative analgesia and functional recovery in association with PENG block during the first postoperative day, although it had worse short-term pain scores. Based on these results, it is reasonable to consider LFCN block as a valid alternative to WI or even a complementary technique added to WI to enhance skin analgesia during the first 24 h after THA. Future studies are expected to confirm this hypothesis and find the best combination between PENG block and other techniques to enhance analgesia after THA.

Chemotherapy increases the prevalence of radiotherapy-related trismus in head and neck cancer patients: A systematic review and meta-analysis.

Background: To evaluate the influence of chemotherapy on the prevalence of trismus in irradiated head and neck cancer patients. Material and Methods: This systematic review guided by PRISMA-2020 and registered in PROSPERO (CRD42021255377) screened 963 articles in 7 scientific-databases (PubMed, Lilacs, Livivo, Scopus, Embase, Web of Science, EBSCO) and 3 grey-literature databases (Open Grey, Google Scholar, ProQuest) and eight articles were included for qualitative synthesis, meta-analysis (combined odds ratio, inverse variance method plus random effects), heterogeneity analysis (I² and Tau²), one-of-out evaluation and publication bias analysis (Eggs' and Begg's tests) (RevMan®, p<0.05). The Newcastle-Ottawa Quality Assessment Scale Cohort Studies was used to assess the risk of bias (RoB). The classification assessment, development, and recommendations (GRADE) approach was used to assess the certainty of evidence. Results: The eight articles evaluated 1474 patients treated with chemoradiotherapy and 858 patients treated with radiotherapy. Five articles had low RoB, and three had high RoB. Chemoradiotherapy significantly (p=0.0003) increased the prevalence of trismus (OR=2.55, 95% CI = 1.53-4.23) compared to radiotherapy, with significant (p=0.010) but low heterogeneity (I²=59%;Tau²=0.29). There was no significant risk of publication bias, one-out analysis showed no significant difference between studies, and GRADE showed a moderate level of evidence. Trismus was directly associated to worse quality of life. Conclusions: The incidence of trismus increases when chemotherapy is combined with radiotherapy for head and neck cancer, which negatively impacts the quality of life. Key words:Radiotherapy, Chemoradiotherapy, Head and Neck Neoplasms, Trismus, Quality of Life.

Extracorporeal Membrane Oxygenation in Acute Respiratory Failure due to Hemorrhagic Alveolitis in a Patient with Acute Myeloblastic Leukemia.

Introduction. Extracorporeal membrane oxygenation (ECMO) support for severe acute respiratory distress syndrome (ARDS) is nowadays widely used with notable results on the overall survival as reported in the ELSO registry near to 55% at 90 days. This is the reason why ECMO teams force the use of this extreme technique to several populations, even though there is still a lack of data about its use on hematological patients. Case Report. A 39-year-old woman without a history of previous diseases, but a new diagnosis of acute myeloblastic leukemia (AML) was admitted to intensive care unit (ICU) for worsening hypoxia and respiratory acidosis, presenting an ARDS with PaO2/FiO2 < 100 in spontaneous breathing treated with noninvasive ventilation via full-face mask. Meanwhile, chemotherapy was started leading to a severe bone marrow aplasia that was managed with multiple blood and platelet transfusions. These conditions did not allow physicians to start any invasive approaches. After 14 days, ARDS worsened whereas bone marrow recovered, making possible the beginning of an invasive mechanical ventilation, with low positive end-expiratory pressure and a low tidal volume. Moreover, an immediate extracorporeal CO2 removal (ECCO2R) therapy was added. Despite these efforts, no improvement was achieved, and that is why venovenous ECMO throughout femoral-jugular cannulation was applied. A full protective lung ventilation by ultralow tidal volumes was guaranteed. After 2 weeks of ECMO, a gradual weaning from ECMO support was started and completed after two days. No ECMO-related complications were registered. In the end, the patient started her weaning from the mechanical ventilation and reached 12 hours of spontaneous ventilation in oxygen therapy. Discussion. ECMO is used as a rescue therapy in patients affected by severe respiratory failure with life-threatening hypoxia and respiratory acidosis nonresponsive to other maneuvers. However, immunosuppression and coagulopathies of hematological malignancies are considered relative contraindications for ECMO, while long-lasting respiratory failure represents another relative contraindication to extracorporeal support. ECMO could be a valid option to improve the survival of hematological patients with severe ARDS and thrombocytopenia, and management could change case by case, even if high incidence of recurrency.

The Role of TAP/RS Block in Minor Gynecologic Laparoscopic Surgery: A Randomized Clinical Trial.

OBJECTIVES: The aim of the study was to compare, in patients undergoing minor gynecological laparoscopic procedures, the effects of ultrasound (US)-guided transversus abdominis plane (TAP) + rectus sheath (RS) block versus no TAP/RS block in terms of post-surgical pain control using the numeric pain rating scale (NRS) and the degree of patient satisfaction, according to the main goals of Early Recovery After Surgery (ERAS) programs. The primary outcome is to value the postoperative abdominal pain using NRS in both groups. Secondary outcomes are to evaluate blood values, presence of postoperative nausea and vomiting (PONV), postoperative ileus, level of patient expected satisfaction, time of discharge, length of stay (LOS), and the amounts of additional analgesics required. DESIGN: In this prospective randomized controlled trial, patients were randomly assigned to loco-regional anesthesia (LRA) group, who received TAP and RS block under US guidance, or no loco-regional anesthesia (N-LRA) group. Enrolled patients were randomized 1:1 to either receive bilateral TAP/RS block with ropivacaine or sham treatment (patches were applied on the abdominal wall of the patients under general anesthesia). PARTICIPANTS: All patients aged between 18 and 75 years, with ASA (American Society of Anesthesiologists) physical status 1-2, undergoing laparoscopic minor gynecological surgery, were enrolled. SETTING: The study was conducted to the University of Campus Bio-Medico Hospital of Rome. METHODS: Half an hour before surgery, all patients received gabapentin 300 mg per os. Once the patient underwent general anesthesia, US-guided bilateral TAP/RS block was performed by the anesthesiology team, while the uterine manipulator was positioned by a gynecology resident (not involved in the study). In the operative room, all patients received the same standardized anesthetic regimen. Postoperative abdominal pain was assessed at rest, after palpation, during movement, and after a cough by evaluating the patient at 6, 12, 18, 24, 36, 48, and 72 h after surgery, using the NRS from 0 to 10 in both groups. The amount of drug used for analgesia in the first 48 h after surgery was recorded. Moreover, hemoglobin, white blood cells, and c-reactive protein levels were recorded at 24, 48, and 72 h. The presence of PONV and the postoperative ileus was recorded throughout convalescence. The expected level of patient satisfaction at discharge and finally the LOS were assessed. LIMITATIONS: The major weakness of this study is that 60 mL of 0.5% ropivacaine was administered to each patient, without considering weight differences, yet contemporary literature rarely suggests volume/dose titration in fascial blocks. RESULTS: A total of 104 women, undergoing gynecological minor laparoscopic surgery, were enrolled and assigned to LRA group (53 pts) and N-LRA group (51 pts). Postoperative pain was significantly reduced in patients who received TAP/RS block. A reduction in the intake of non-steroidal anti-inflammatory drugs after surgery was registered in LRA group (p < 0.01). Moreover, a significant reduction of LOS (45.97 ± 9.87 vs. 65.08 ± 17.32 h; p < 0.01) and PONV was observed in the LRA group, as well as a better level of patient satisfaction at discharge (9.43 ± 0.94 vs. 8.26 ± 1.19; p < 0.01), compared to the N-LRA group. CONCLUSIONS: US-guided TAP and RS block significantly reduces postoperative pain after minor gynecologic laparoscopic surgery and improves patients' post-operative recovery.

Avaliação da sonolência e queixas de sono dos estudantes de odontologia da Universidade Federal do Ceará / Evaluation of sleepness and sleep complaints among dentistry students from the federal University of Ceará / Evaluación de somnolencia y quejas de sueño en estudiantes de odontología de la Universidad Federal de Ceará

O sono é um estado essencial para sobrevivência humana, ele exerce função biológica, restauradora e de conservação energética do organismo, promovendo equilíbrio físico e mental. Alta prevalência da má qualidade de sono e sonolência diurna excessiva (SDE) têm sido relatadas por estudantes universitários de diversos cursos, ocasionando prejuízos na concentração e queda dos rendimentos acadêmicos. O objetivo deste trabalho foi avaliar a qualidade de sono, a SDE e suas possíveis associações com sintomas depressivos em estudantes de odontologia. Foi realizado um estudo transversal e descritivo com 251 alunos do curso de odontologia da Faculdade de Farmácia, Odontologia e Enfermagem da Universidade Federal do Ceará. Os instrumentos utilizados foram o Índice de Qualidade de Sono de Pittsburgh (IQSP), Escala de Sonolência de Epworth (ESE) e Inventário de Depressão de Beck (IDB). Verificou-se uma alta prevalência de má qualidade de sono (53,4%) e SDE (35,1%) entre os estudantes, sem diferença significante em relação ao sexo para ambas. Foi encontrada correlação positiva entre IDB com IQSP e ESE (r = 0,478; p = 0,000 e r = 0,202; p = 0,000, respectivamente). Os resultados mostraram uma alta prevalência de má qualidade de sono e SDE e ambos os achados apresentaram associação com sintomas depressivos.

Sleep is an essential state for human survival. It has a biological, restorative and energy conservation function for the organism, promoting physical and mental balance. A high prevalence of poor sleep quality and excessive daytime sleepiness (EDS) has been reported among university students from different courses, causing impaired concentration and a drop in academic performance. This study evaluates sleep quality, EDS and their possible associations with depressive symptoms in dentistry students. A cross-sectional descriptive research was conducted with 251 students from the Dentistry Course at the School of Pharmacy, Dentistry and Nursing, Federal University of Ceará. Variables of interest were assessed by Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS) and Beck Depression Inventory (BDI). Results show a high prevalence of poor sleep quality (53.4%) and EDS (35.1%) among students, with no significant difference regarding gender. BDI had a positive correlation with PSQI and ESS (r= 0.478, p= 0.000; and r= 0.202, p =0.000, respectively). Both findings were associated with depressive symptoms.

El sueño es un estado esencial para la supervivencia humana, tiene una función biológica, reparadora y de conservación de energía para el organismo, favoreciendo el equilibrio físico y mental. Se ha reportado una alta prevalencia de mala calidad del sueño y somnolencia diurna excesiva (SDE) en estudiantes universitarios de diferentes carreras que provoca alteración de la concentración y caída del rendimiento académico. El objetivo de este trabajo fue evaluar la calidad del sueño, la SDE y sus posibles asociaciones con síntomas depresivos en estudiantes de odontología. Se realizó un estudio descriptivo transversal con 251 estudiantes de la carrera de Odontología de la Facultad de Farmacia, Odontología y Enfermería de la Universidad Federal de Ceará. Los instrumentos utilizados fueron el Índice de Calidad del Sueño de Pittsburgh (PSQI), la Escala de Somnolencia de Epworth (ESS) y el Inventario de Depresión de Beck (BDI). Hubo una alta prevalencia de mala calidad del sueño (53,4%) y SDE (35,1%) entre los estudiantes, sin diferencia significativa en relación con el género para ambos. Se encontró una correlación positiva entre BDI con PSQI y ESS (r= 0,478; p= 0,000 y r= 0,202; p = 0,000, respectivamente). Los resultados mostraron una alta prevalencia de mala calidad del sueño y SDE, y ambos hallazgos se asociaron con síntomas depresivos.

Salivary immunoglobulin levels and periodontal indices in Brazilian children with and without type 1 diabetes

Abstract This cross-sectional study evaluated the association between salivary immunoglobulins, plaque index, and gingival index in Brazilian children with and without type 1 diabetes mellitus (DM1). The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for the reporting of observational studies was followed. The DM1 group had 38 children, and an equal number of volunteers matched by sex and age were recruited as controls. Clinical examination was performed for plaque index and gingival index determination. Non-stimulated whole saliva was collected. Concentrations of IgA, IgG, and IgM were determined by ELISA test. Data were tested by the Kolmogorov-Smirnov, Mann-Whitney, and Spearman tests and a multiple linear regression model (p<0.05) was performed. Gingival index was higher in the Control (DM1: 0.16±0.17; Control: 0.24±0.23, p=0.040). In DM1, there was a correlation between IgA and age (rho=0.371, p=0.024), IgM and IgG (rho=0.459, p=0.007), and IgM and gingival index (rho=0.394, p=0.014). In DM1, multiple linear regression showed that age (p=0.041; β=0.363), gingival index (p=0.041; β=0.398), and plaque index (p=0.008; β=-0.506) were good predictors of IgA levels in saliva. Thus, IgA was the only researched immunoglobulin that was directly associated with plaque and gingival indices in Brazilian children with DM1, but not in control subjects.

Mandibular assessment of panoramic radiographs for sex identification / Análise do dimorfismo sexual através de índices radiomorfométricos em radiografias panorâmicas

ABSTRACT Sex determination plays a crucial role in the post-mortem identification of human remains. One effective approach for obtaining sex-related data is to use measurements of anatomical structures such as the mandible. This study aimed to evaluate the potential of mandibular radiomorphometric indices from panoramic radiographs (PRs) for the identification of sexual dimorphism. The study sample included 300 PRs of individuals aged 51 to 80 years from the northeastern region of Brazil. Four linear measures and three numerical indices were analyzed with Inkscape® version 1.0.1 for Windows by two blinded evaluators. After statistical analysis, the results showed that the linear measurements obtained from PRs are a reliable method for sex identification. However, the calculated indices of these measurements exhibited lower efficacy for the same purpose. Therefore, PRs proved to be a valuable method for sexual identification through mandibular assessment.

RESUMO A determinação do sexo é um dado importante para a identificação post-mortem de um indivíduo ou de restos mortais humanos. Uma maneira de adquirir dados quanto ao sexo é utilizar mensurações de estruturas como a mandíbula. O objetivo principal deste estudo é avaliar a utilização de índices radiomorfométricos de mandíbulas para a identificação de dimorfismo sexual, através de radiografias panorâmicas. O estudo foi realizado em exames radiográficos panorâmicos de 300 indivíduos entre 51 e 80 anos, residentes do Nordeste brasileiro. Foram analisadas quatro medidas lineares e três índices numéricos no software Inkscape® versão 1.0.1 para Windows, por dois avaliadores cegos. Após análise estatística, os resultados demostraram que as medidas lineares obtidas se configuram como um método seguro para a identificação sexual. Entretanto, os índices obtidos através destas medidas demostraram menor eficiência para o mesmo fim. Logo, as radiografias panorâmicas podem ser utilizadas como método eficaz para a obtenção da caracterização sexual através da mandíbula.

Management of Cancer Therapy-Induced Oral Mucositis Using Photobiomodulation Therapy: An Overview of Systematic Reviews.

Objective: To systematically summarize the evidence for photobiomodulation therapy (PBMT) in the prevention and treatment of oral mucositis (OM) in patients undergoing cancer treatment. An electronic search was conducted in 8 databases and grey literature. Background: PBMT is recommended for the management of OM resulting from cancer treatment, with several systematic reviews (SRs) being published in recent years on this topic. Methods: Only SRs with outcomes from clinical trials were included, with no language or year restriction. The AMSTAR 2 tool was used to assess the methodological quality of the SRs. Results: Five thousand eight hundred fifty-six references were found, and 16 were selected for this review. OM prevention and treatment were favorable for PBMT in most studies, with a significant reduction in OM severity. Most studies obtained moderate confidence. Conclusions: PBMT represents an effective strategy in the management of OM, and this evidence is supported by studies with acceptable methodological quality.

Identification of potential inhibitors of casein kinase 2 alpha of Plasmodium falciparum with potent in vitro activity.

Drug resistance to commercially available antimalarials is a major obstacle in malaria control and elimination, creating the need to find new antiparasitic compounds with novel mechanisms of action. The success of kinase inhibitors for oncological treatments has paved the way for the exploitation of protein kinases as drug targets in various diseases, including malaria. Casein kinases are ubiquitous serine/threonine kinases involved in a wide range of cellular processes such as mitotic checkpoint signaling, DNA damage response, and circadian rhythm. In Plasmodium, it is suggested that these protein kinases are essential for both asexual and sexual blood-stage parasites, reinforcing their potential as targets for multi-stage antimalarials. To identify new putative PfCK2α inhibitors, we utilized an in silico chemogenomic strategy involving virtual screening with docking simulations and quantitative structure-activity relationship predictions. Our investigation resulted in the discovery of a new quinazoline molecule (542), which exhibited potent activity against asexual blood stages and a high selectivity index (>100). Subsequently, we conducted chemical-genetic interaction analysis on yeasts with mutations in casein kinases. Our chemical-genetic interaction results are consistent with the hypothesis that 542 inhibits yeast Cka1, which has a hinge region with high similarity to PfCK2α. This finding is in agreement with our in silico results suggesting that 542 inhibits PfCK2α via hinge region interaction.

TP53 gain-of-function mutation modulates the immunosuppressive microenvironment in non-HPV-associated oral squamous cell carcinoma.

BACKGROUND: TP53, the most mutated gene in solid cancers, has a profound impact on most hallmarks of cancer. Somatic TP53 mutations occur in high frequencies in head and neck cancers, including oral squamous cell carcinoma (OSCC). Our study aims to understand the role of TP53 gain-of-function mutation in modulating the tumor immune microenvironment (TIME) in OSCC. METHODS: Short hairpin RNA knockdown of mutant p53R172H in syngeneic oral tumors demonstrated changes in tumor growth between immunocompetent and immunodeficient mice. HTG EdgeSeq targeted messenger RNA sequencing was used to analyze cytokine and immune cell markers in tumors with inactivated mutant p53R172H. Flow cytometry and multiplex immunofluorescence (mIF) confirmed the role of mutant p53R172H in the TIME. The gene expression of patients with OSCC was analyzed by CIBERSORT and mIF was used to validate the immune landscape at the protein level. RESULTS: Mutant p53R172H contributes to a cytokine transcriptome network that inhibits the infiltration of cytotoxic CD8+ T cells and promotes intratumoral recruitment of regulatory T cells and M2 macrophages. Moreover, p53R172H also regulates the spatial distribution of immunocyte populations, and their distribution between central and peripheral intratumoral locations. Interestingly, p53R172H-mutated tumors are infiltrated with CD8+ and CD4+ T cells expressing programmed cell death protein 1, and these tumors responded to immune checkpoint inhibitor and stimulator of interferon gene 1 agonist therapy. CIBERSORT analysis of human OSCC samples revealed associations between immune cell populations and the TP53R175H mutation, which paralleled the findings from our syngeneic mouse tumor model. CONCLUSIONS: These findings demonstrate that syngeneic tumors bearing the TP53R172H gain-of-function mutation modulate the TIME to evade tumor immunity, leading to tumor progression and decreased survival.

Effectiveness of low-intensity laser photobiomodulation in reducing inflammatory events (pain, edema, and trismus) after orthognathic surgery: a systematic review and meta-analysis of randomized clinical trials.

OBJECTIVE: This systematic review aimed to answer whether, in (P) individuals undergoing orthognathic surgery, (I) low-level laser therapy (LLLT) during or shortly after the surgical procedure compared to (C) pharmacologic therapy alone or no therapy for improvement of post-intervention complications relieves (O) postoperative inflammatory events in (S) randomized clinical trials. MATERIAL AND METHODS: A preliminary electronic search was conducted for references with language following a Latin (Roman) alphabet in seven databases index, and gray literature without restriction on language or publication period. Risk of bias was performed by RoB 2.0 tool, and meta-analysis used mean differences (MD) for edema and mouth opening and standardized mean differences (SMD) for pain scores (p < 0.05, Revman®). RESULTS: A total of 91 control patients and 114 LLLT patients were included. The wavelengths ranged from 660 to 940 nm, and the applied energy density was between 5 and 100 J/cm2 at mostly extraoral distributed points. LLLT significantly reduced edema (MD = - 4.27, CI95% - 5.13 to - 3.41 mm) in the period from 5 days to 2 weeks postoperatively (p < 0.001) and showed strongly reduced pain scores (SMD = - 1.37, I95% = - 1.99 to - 0.75) between 1 day and 5 weeks (p < 0.001), without significantly interfering with mouth opening (p = 0.110). Despite the low risk of bias, high heterogeneity among studies (I2 > 70%) and small sample sizes made the certainty of GRADE evidence low. CONCLUSION: This SR demonstrated that LLLT effectively controls pain and edema after orthognathic surgery. CLINICAL RELEVANCE: Systematic review that summarizes the use of photobiomodulation on orthognathic surgery.