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1.
Front Oncol ; 14: 1360737, 2024.
Article in English | MEDLINE | ID: mdl-38601755

ABSTRACT

Locally advanced breast cancer poses significant challenges to the multidisciplinary team, in particular with hormone receptor (HR) positive, HER2-negative tumors that classically yield lower pathological complete responses with chemotherapy. The increasingly significant use of CDK 4/6 inhibitors (CDK4/6i) plus endocrine therapy (ET) in different breast cancer settings has led to clinical trials focusing on this strategy as a primary treatment, with promising results. The impact of the microbiota on cancer, and vice-versa, is an emerging topic in oncology. The authors report a clinical case of a postmenopausal female patient with an invasive breast carcinoma of the right breast, Luminal B-like, staged as cT4cN3M0 (IIIB). Since the lesion was considered primarily inoperable, the patient started letrozole and ribociclib. Following 6 months of systemic therapy, the clinical response was significant, and surgery with curative intent was performed. The final staging was ypT3ypN2aM0, R1, and the patient started adjuvant letrozole and radiotherapy. This case provides important insights on primary CDK4/6i plus ET in locally advanced unresectable HR+/HER2- breast cancer and its potential implications in disease management further ahead. The patient's gut microbiota was analyzed throughout the disease course and therapeutic approach, evidencing a shift in gut microbial dominance from Firmicutes to Bacteroidetes and a loss of microbial diversity following 6 months of systemic therapy. The analysis of the intratumoral microbiota from the surgical specimen revealed high microbial dissimilarity between the residual tumor and respective margins.

2.
Cureus ; 16(3): e55573, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38576627

ABSTRACT

This narrative review explores the application of point-of-care ultrasound (POCUS) in palliative care and its feasibility in home care settings. POCUS has the potential to streamline diagnostic strategies without patient transfer to the hospital, expedite timely symptomatic relief, and reduce complications from specific palliative interventions. The advent of handheld ultrasound devices has made it an attractive diagnostic and interventional adjunct in acute palliative care. POCUS has gained widespread acceptance as part of routine care in emergency medicine and intensive care, guiding certain procedures and increasing their safety. The modernization and miniaturization of ultrasound equipment have made ultra-portable devices available, allowing for better-quality images at affordable prices. Handheld devices have the potential to revolutionize everyday clinical practice in home-based palliative care, contributing to important bedside clinical decisions. Palliative care patients often require diagnostic examinations in the last months of their lives, with CT being the most frequently performed imaging procedure. However, CT imaging is associated with high costs and burdens, leading to increased suffering and impaired quality of life. Clinical ultrasound, a dialogic imaging modality, offers a safer and more efficient approach to palliative care. POCUS applications, which are cost-effective, non-invasive, and well-tolerated, can be used to improve patient satisfaction and diagnostic understanding. POCUS is a valuable tool in palliative care, improving diagnostic accuracy and reducing the time to diagnosis for various pathologies. It is a standard of care for many procedures and improves patient safety. However, there are limitations to POCUS in palliative care, such as operator-dependent examination variability and limited availability of trained professionals. To overcome these limitations, palliative care physicians should receive mandatory training in POCUS, which can be incorporated into the core curriculum. Additionally, ultrasound teleconsulting can assist less experienced examiners in real-time examinations. The literature on POCUS in palliative care is limited, but research on patient-oriented outcomes is crucial. POCUS should be considered a supplement to good clinical reasoning and regulated radiological evaluations.

3.
Int J Mol Sci ; 25(6)2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38542390

ABSTRACT

In arterial hypertension, the dysregulation of several metabolic pathways is closely associated with chronic immune imbalance and inflammation progression. With time, these disturbances lead to the development of progressive disease and end-organ involvement. However, the influence of cholecalciferol on metabolic pathways as a possible mechanism of its immunomodulatory activity in obesity-related hypertension is not known. In a phase 2, randomized, single-center, 24-week trial, we evaluated, as a secondary outcome, the serum metabolome of 36 age- and gender-matched adults with obesity-related hypertension and vitamin D deficiency, before and after supplementation with cholecalciferol therapy along with routine medication. The defined endpoint was the assessment of circulating metabolites using a nuclear magnetic resonance-based metabolomics approach. Univariate and multivariate analyses were used to evaluate the systemic metabolic alterations caused by cholecalciferol. In comparison with normotensive controls, hypertensive patients presented overall decreased expression of several amino acids (p < 0.05), including amino acids with ketogenic and glucogenic properties as well as aromatic amino acids. Following cholecalciferol supplementation, increases were observed in glutamine (p < 0.001) and histidine levels (p < 0.05), with several other amino acids remaining unaffected. Glucose (p < 0.05) and acetate (p < 0.05) decreased after 24 weeks in the group taking the supplement, and changes in the saturation of fatty acids (p < 0.05) were also observed, suggesting a role of liposoluble vitamin D in lipid metabolism. Long-term cholecalciferol supplementation in chronically obese and overweight hypertensives induced changes in the blood serum metabolome, which reflected systemic metabolism and may have fostered a new microenvironment for cell proliferation and biology. Of note, the increased availability of glutamine may be relevant for the proliferation of different T-cell subsets.


Subject(s)
Hypertension , Vitamin D Deficiency , Adult , Humans , Cholecalciferol/pharmacology , Cholecalciferol/therapeutic use , Glutamine/therapeutic use , Glucose/therapeutic use , Vitamin D/therapeutic use , Obesity/complications , Obesity/drug therapy , Dietary Supplements , Vitamin D Deficiency/complications , Hypertension/complications , Hypertension/drug therapy , Amino Acids/metabolism , Double-Blind Method
5.
Article in English | MEDLINE | ID: mdl-38479630

ABSTRACT

BACKGROUND: X-linked agammaglobulinemia (XLA) is an inborn error of immunity that renders boys susceptible to life-threatening infections due to loss of mature B cells and circulating immunoglobulins. It is caused by defects in the gene encoding the Bruton tyrosine kinase (BTK) that mediates the maturation of B cells in the bone marrow and their activation in the periphery. This paper reports on a gene editing protocol to achieve "knock-in" of a therapeutic BTK cassette in hematopoietic stem and progenitor cells (HSPCs) as a treatment for XLA. METHODS: To rescue BTK expression, this study employed a clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 system that creates a DNA double-strand break in an early exon of the BTK locus and an adeno-associated virus 6 virus that carries the donor template for homology-directed repair. The investigators evaluated the efficacy of the gene editing approach in HSPCs from patients with XLA that were cultured in vitro under B-cell differentiation conditions or that were transplanted in immunodeficient mice to study B-cell output in vivo. RESULTS: A (feeder-free) B-cell differentiation protocol was successfully applied to blood-mobilized HSPCs to reproduce in vitro the defects in B-cell maturation observed in patients with XLA. Using this system, the investigators could show the rescue of B-cell maturation by gene editing. Transplantation of edited XLA HSPCs into immunodeficient mice led to restoration of the human B-cell lineage compartment in the bone marrow and immunoglobulin production in the periphery. CONCLUSIONS: Gene editing efficiencies above 30% could be consistently achieved in human HSPCs. Given the potential selective advantage of corrected cells, as suggested by skewed X-linked inactivation in carrier females and by competitive repopulating experiments in mouse models, this work demonstrates the potential of this strategy as a future definitive therapy for XLA.

6.
BMC Psychol ; 12(1): 63, 2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38326847

ABSTRACT

BACKGROUND: Childhood emotional disorders (EDs; i.e., anxiety and depressive disorders) are currently a public health concern. Their high prevalence, long-term effects, and profound influence on the lives of children and families highlight the need to identify and treat these disorders as early and effectively as possible. This clinical trial will examine the efficacy of a blended version (i.e., combining face-to-face and online sessions into one treatment protocol) of the Unified Protocol for Children (the "Emotion Detectives In-Out" program). This program is a manualized cognitive-behavioral therapy for the transdiagnostic treatment of EDs in children aged 7 to 12 years that aims to reduce the intensity and frequency of strong and aversive emotional experiences by helping children learn how to confront those emotions and respond to them in more adaptive ways. METHODS: This study is designed as a multicenter equivalence randomized controlled parallel-group two-arm trial comparing the Emotion Detectives In-Out program with an evidenced-based group intervention for children with anxiety disorders (the Coping Cat program). Participants will be children aged between 7 and 12 years with an anxiety disorder or with clinically significant anxiety symptoms as well as one of their parents or a legal representative. A minimum sample size of 138 children (69 per group) is needed to test whether the efficacy of the proposed intervention is equivalent to that of the well-established Coping Cat intervention. DISCUSSION: We expect Emotion Detectives In-Out to be a feasible and efficacious alternative intervention for treating children's EDs by allowing for a greater increase in children's access to care. A blended format is expected to overcome common barriers to treatment (e.g., parents´ lack of time to attend regular sessions) and make the intervention more accessible to families. TRIAL REGISTRATION: The clinical trial is registered at ClinicalTrials.gov (Identifier: NCT05747131, date assigned February 28, 2023).


Subject(s)
Anxiety Disorders , Emotions , Mood Disorders , Child , Humans , Anxiety Disorders/diagnosis , Anxiety Disorders/therapy , Mood Disorders/diagnosis , Mood Disorders/therapy , Portugal , Treatment Outcome , Randomized Controlled Trials as Topic , Multicenter Studies as Topic
7.
J Hum Kinet ; 90: 71-88, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38380297

ABSTRACT

Human locomotion on water depends on the force produced by the swimmer to propel the body forward. Performance of highly complex motor tasks like swimming can yield minor variations that only nonlinear analysis can be sensitive enough to detect. The purpose of the present study was to examine the nonlinear properties of the hand/feet forces and describe their variations across the four competitive swimming strokes performing segmental and full-body swimming. Swimmers performed all-out bouts of 25 m in the four swimming strokes, swimming the full-body stroke, with the arm-pull only and with the leg kicking only. Hand/foot force and swimming velocity were measured. The Higuchi's fractal dimension (HFD) and sample entropy (SampEn) were used for the nonlinear analysis of force and velocity. Both the arm-pull and leg kicking alone were found to produce similar peak and mean hand/foot forces as swimming the full-body stroke. Hand force was more complex in breaststroke and butterfly stroke; conversely, kicking conditions were more complex in front crawl and backstroke. Moreover, the arm-pull and kicking alone tended to be more complex (higher HFD) but more predictable (lower SampEn) than while swimming the full-body stroke. There was no loss of force production from segmental swimming to the full-body counterpart. In conclusion, the number of segments in action influences the nonlinear behavior of the force produced and, when combining the four limbs, the complexity of the hand/foot force tends to decrease.

8.
Int J Mol Sci ; 25(3)2024 Jan 29.
Article in English | MEDLINE | ID: mdl-38338923

ABSTRACT

The aetiology of acute appendicitis (AA), the most frequent abdominal surgical emergency, is still unclarified. Recent epidemiologic, clinical and laboratorial data point to an allergic component in the pathophysiology of AA. Mastocytes participate in the Th2 immune response, releasing inflammatory mediators from their granules upon stimulation by IgE-specific antigens. Among the well-known mediators are histamine, serotonin and tryptase, which are responsible for the clinical manifestations of allergies. We conducted a prospective single-centre study to measure histamine and serotonin (commercial ELISA kit) and tryptase (ImmunoCAP System) concentrations in appendicular lavage fluid (ALF) and serum. Consecutive patients presenting to the emergency department with a clinical diagnosis of AA were enrolled: 22 patients with phlegmonous AA and 24 with gangrenous AA The control group was composed of 14 patients referred for colectomy for colon malignancy. Appendectomy was performed during colectomy. Tryptase levels were strikingly different between histological groups, both in ALF and serum (p < 0.001); ALF levels were higher than serum levels. Tryptase concentrations in ALF were 109 times higher in phlegmonous AA (APA) (796.8 (194.1-980.5) pg/mL) and 114 times higher in gangrenous AA (AGA) (837.4 (272.6-1075.1) pg/mL) than in the control group (7.3 (4.5-10.3) pg/mL. For the diagnosis of AA, the discriminative power of serum tryptase concentration was good (AUC = 0.825), but discriminative power was weak (AUC = 0.559) for the differential diagnosis between APA and AGA. Mastocytes are involved in AA during clinical presentations of both phlegmonous and gangrenous appendicitis, and no significant differences in concentration were found. No differences were found in serum and ALF concentrations of histamine and serotonin between histological groups. Due to their short half-lives, these might have elapsed by the time the samples were collected. In future research, these determinations should be made immediately after appendectomy. Our findings confirm the hypersensitivity type I reaction as an event occurring in the pathogenesis of AA: tryptase levels in ALF and serum were higher among patients with AA when compared to the control group, which is in line with a Th2 immune response and supports the concept of the presence of an allergic reaction in the pathogenesis of acute appendicitis. Our results, if confirmed, may have clinical implications for the treatment of AA.


Subject(s)
Appendicitis , Hypersensitivity , Humans , Appendicitis/diagnosis , Appendicitis/surgery , Appendicitis/etiology , Tryptases , Histamine , Prospective Studies , Serotonin , Hypersensitivity/complications
9.
Curr Issues Mol Biol ; 46(1): 485-497, 2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38248333

ABSTRACT

Oral squamous cell carcinoma (OSCC) is a common and highly aggressive dog tumor known for its local invasiveness and metastatic potential. Understanding the molecular mechanisms driving the development and progression of OSCC is crucial for improving diagnostic and therapeutic strategies. Additionally, spontaneous oral squamous cell carcinomas in dogs are an excellent model for studying human counterparts. In this study, we aimed to investigate the significance of two key molecular components, Cox-2 and EGFR, in canine OSCC. We examined 34 tumor sections from various dog breeds to assess the immunoexpression of Cox-2 and EGFR. Our findings revealed that Cox-2 was highly expressed in 70.6% of cases, while EGFR overexpression was observed in 44.1%. Cox-2 overexpression showed association with histological grade of malignancy (HGM) (p = 0.006) and EGFR with vascular invasion (p = 0.006). COX-2 and EGFR concurrent expression was associated with HGM (p = 0.002), as well as with the presence of vascular invasion (p = 0.002). These data suggest that Cox-2 and EGFR could be promising biomarkers and potential therapeutic targets, opening avenues for developing novel treatment strategies for dogs affected by OSCC. Further studies are warranted to delve deeper into these findings and translate them into clinical practice.

10.
Int J Pharm ; 649: 123642, 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-38029863

ABSTRACT

Tetracyclines (TCs) are a class of broad-spectrum antibacterial agents recognized for their multifaceted properties, including anti-inflammatory, angiogenic and osteogenic effects. This versatility positions them as suitable candidates for drug repurposing, benefitting from well-characterized safety and pharmacological profiles. In the attempt to explore both their antibacterial and pleiotropic effects locally, innovative therapeutic strategies were set on engineering tetracycline-loaded micro and nanoparticles to tackle a vast number of clinical applications. Moreover, the conjoined drug carrier can function as an active component of the therapeutic approach, reducing off-target effects and accumulation, synergizing to an improvement of the therapeutic efficacy. In this comprehensive review we will critically evaluate recent advances involving the use of tetracyclines loaded onto micro- or nanoparticles, intended for biomedical applications, and discuss emerging approaches and current limitations associated with these drug carriers. Owing to their distinctive physical, chemical, and biological properties, these novel carriers have the potential to become a platform technology in personalized regenerative medicine and other therapeutic applications.


Subject(s)
Nanoparticles , Tetracyclines , Tetracyclines/pharmacology , Drug Delivery Systems , Drug Carriers/chemistry , Anti-Bacterial Agents , Nanoparticles/chemistry
12.
Cureus ; 15(10): e47461, 2023 Oct.
Article in English | MEDLINE | ID: mdl-38021888

ABSTRACT

Primary hyperparathyroidism (PHPT) can be associated with osteoporosis (OP) and fractures. We present a case of a 49-year-old male referred to our osteoporosis outpatient clinic due to a right femur osteoporotic fracture. At the age of 38, a right plantar nodular lesion was excised, and its histology was compatible with a deep dermis nodule formed by mononuclear and giant osteoclast-like cells. He has reported osteoporotic fractures since age 39 and renal colic episodes since age 45. His father had lipomas and renal colic episodes, and his paternal grandmother had lipomas. The laboratory evaluation was compatible with PHPT. A cervical ultrasound showed a 10mm single solid nodule in the left thyroid lobe, strongly hypoechogenic, with microcalcifications. Its cytology showed parathyroid tissue without atypia. Parathyroid scintigraphy had no uptake. A dual-energy X-ray absorptiometry scan showed a femoral neck Z-score of -4.3. He started alendronate/cholecalciferol (70mg/5600IU) weekly. He was submitted to a left hemithyroidectomy. Its histology showed an intrathyroidal parathyroid adenoma. Ectopic parathyroid adenomas are rare, of which 0.7%-6% are intrathyroidal. The excised foot lesion could be a brown tumour. Furthermore, calcium metabolism evaluation at that time might have allowed a PHPT diagnosis and its morbidity prevention. Osteoporotic fractures in young men must alert to secondary OP.

13.
Cureus ; 15(10): e46903, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37954778

ABSTRACT

Multiple primary malignancies (MPMs) are defined as two or more histopathologically distinct malignancies in the same individual. MPMs are classified as synchronous when tumors are diagnosed within six months of each other. The most common malignancies in MPMs are melanoma, breast, lung, and prostate cancer. Synchronous lymphoma and solid tumors are relatively rare. In these cases, a multi-disciplinary approach to treatment is essential. The early detection of additional primary malignancies such as myeloid and lymphatic tumors will enable prompt management with curative intent. The authors present a case of diffuse B-cell non-Hodgkin lymphoma and invasive lobular breast carcinoma presented as a chylous pleural effusion.

14.
BMC Complement Med Ther ; 23(1): 356, 2023 Oct 07.
Article in English | MEDLINE | ID: mdl-37805488

ABSTRACT

BACKGROUND: Carboxymethylated Lasiodiplodan (LaEPS-C), Lasiodiplodia theobromae ß-glucan exopolysaccharide derivative, has a well-known range of biological activities. Compared to LaEPS-C, its fractions, Linear (LLaEPS-C) and Branched (BLaEPS-C), have biological potentialities scarcely described in the literature. So, in this study, we investigate the immunomodulatory, antiviral, antiproliferative, and anticoagulant activities of LLaEPS-C and BLaEPS-C and compare them to the LaEPS-C. METHODS: LaEPS was obtained from L. theobromae MMBJ. After carboxymethylation, LaEPS-C structural characteristics were confirmed by Elementary Composition Analysis by Energy Dispersive X-Ray Detector (EDS), Fourier Transform Infrared (FTIR), and Nuclear Magnetic Resonance (NMR). The immunomodulatory activity on cytokine secretion was evaluated in human monocyte-derived macrophage cultures. The antiviral activity was evaluated by Hep-2 cell viability in the presence or absence of hRSV (human respiratory syncytial virus). In vitro antiproliferative activity was tested by sulforhodamine B assay. The anticoagulant activity was determined by APTT (Activated Partial Thromboplastin Time) and PT (Prothrombin Time). RESULTS: LaEPS-C showed low macrophage cell viability only at 100 µg/mL (52.84 ± 24.06, 48 h), and LLaEPS-C presented no effect. Conversely, BLaEPS-C showed cytotoxicity from 25 to 100 µg/mL (44.36 ± 20.16, 40.64 ± 25.55, 33.87 ± 25.16; 48 h). LaEPS-C and LLaEPS-C showed anti-inflammatory activity. LaEPS-C presented this at 100 µg/mL (36.75 ± 5.53, 48 h) for IL-10, and LLaEPS-C reduces TNF-α cytokine productions at 100 µg/mL (18.27 ± 5.80, 48 h). LLaEPS-C showed an anti-hRSV activity (0.7 µg/ml) plus a low cytotoxic activity for Hep-2 cells (1.4 µg/ml). LaEPS-C presented an antiproliferative activity for NCI-ADR/RES (GI50 65.3 µg/mL). A better PT was achieved for LLaEPS-C at 5.0 µg/mL (11.85 ± 0.87s). CONCLUSIONS: These findings demonstrated that carboxymethylation effectively improves the biological potential of the LaEPS-C and their fractions. From those polysaccharides tested, LLaEPS provided the best results with low toxicity for anti-inflammatory, antiviral, and anticoagulant activities.


Subject(s)
Cytokines , Polysaccharides , Humans , Polysaccharides/pharmacology , Polysaccharides/chemistry , Anti-Inflammatory Agents/pharmacology , Anticoagulants/pharmacology , Antiviral Agents/pharmacology
15.
J Biomech ; 160: 111815, 2023 Sep 29.
Article in English | MEDLINE | ID: mdl-37783185

ABSTRACT

The purpose of this study was to compare the in-water force of young competitive swimmers using tethered swimming and differential pressure sensors. Thirty-one swimmers (16 girls and 15 boys) were randomly assigned to perform two in-water tests. Swimmers completed two maximum bouts of 25 m front crawl with a differential pressure system and a 30 s maximum bout with an attached load cell (tethered-swimming). The peak force (FPEAK, in N) of dominant and non-dominant upper limbs was retrieved for further analysis. Comparison between methods revealed significant differences in all force variables (p ≤ 0.05) and the biases (mean differences) were large in girls (FPEAK dominant, 45.89 N; FPEAK non-dominant, 43.79 N) and boys (FPEAK dominant, 67.26 N; FPEAK non-dominant, 61.78 N). Despite that, simple linear regression models between the two methods showed significant relationships with a moderate effect in all variables for girls, whereas in boys a high and moderate effect was verified for FPEAK of dominant and non-dominant limbs (respectively). It seems that using pressure sensors and tethered swimming leads to different FPEAK values in young competitive, where correction factors are needed to compare data between both methods.

16.
Cancers (Basel) ; 15(17)2023 Aug 29.
Article in English | MEDLINE | ID: mdl-37686589

ABSTRACT

The most well-characterized hereditary form of gastric cancer is hereditary diffuse gastric cancer (HDGC), an autosomal dominant syndrome characterized by an increased risk of diffuse gastric and lobular breast cancer. HDGC is predominantly caused by germline pathogenic variants in the CDH1 gene, and more rarely in the CTNNA1 gene. Furthermore, the International Gastric Cancer Linkage Consortium (IGCLC) guidelines do not clarify whether or not mixed gastric cancer (with a diffuse component) should be considered in the HDGC genetic testing criteria. We aimed to evaluate the contribution of CTNNA1 and CTNND1 germline variants to HDGC. Additionally, we also intended to compare the frequencies of CDH1 and CTNNA1 (and eventually CTNND1) germline variants between patients with diffuse and mixed gastric carcinomas to evaluate if genetic testing for these genes should or should not be considered in patients with the latter. We analyzed the CDH1 gene in 67 cases affected with early-onset/familial mixed gastric carcinomas and the CTNNA1 and CTNND1 genes in 208 cases with diffuse or mixed gastric cancer who had tested negative for CDH1 pathogenic germline variants. A deleterious CTNNA1 germline variant was found in 0.7% (1/141) of diffuse gastric cancer patients meeting the 2020 IGCLC criteria, as compared to the rate of 2.8% of CDH1 deleterious variants found by us in this setting. No deleterious variants were found in CTNND1, but six variants of uncertain significance were identified in this gene. We did not find any pathogenic CDH1, CTNNA1 or CTNND1 variant in index patients with early-onset/familial mixed gastric cancer, so there is no evidence that supports including this tumor type in the testing criteria for germline variants in these genes. The role of the CTNND1 gene in inherited gastric cancer predisposition is still unclear.

17.
Cells ; 12(18)2023 09 10.
Article in English | MEDLINE | ID: mdl-37759467

ABSTRACT

Tetracyclines (TCs) are a class of broad-spectrum antibiotics with diverse pharmacotherapeutic properties due to their various functional groups being attached to a common core structure. Beyond their antibacterial activity, TCs trigger pleiotropic effects on eukaryotic cells, including anti-inflammatory and potentially osteogenic capabilities. Consequently, TCs hold promise for repurposing in various clinical applications, including bone-related conditions. This study presents the first comprehensive comparison of the in vitro osteogenic potential of four TCs-tetracycline, doxycycline, minocycline, and sarecycline, within human mesenchymal stem cells. Cultures were characterized for metabolic activity, cell morphology and cytoskeleton organization, osteogenic gene expression, alkaline phosphatase (ALP) activity, and the activation of relevant signaling pathways. TCs stimulated actin remodeling processes, inducing morphological shifts consistent with osteogenic differentiation. Osteogenic gene expression and ALP activity supported the osteoinduction by TCs, demonstrating significant increases in ALP levels and the upregulation of RUNX2, SP7, and SPARC genes. Minocycline and sarecycline exhibited the most potent osteogenic induction, comparable to conventional osteogenic inducers. Signaling pathway analysis revealed that tetracycline and doxycycline activate the Wnt pathway, while minocycline and sarecycline upregulated Hedgehog signaling. Overall, the present findings suggest that TCs promote osteogenic differentiation through distinct pathways, making them promising candidates for targeted therapy in specific bone-related disorders.


Subject(s)
Bone Diseases , Heterocyclic Compounds , Mesenchymal Stem Cells , Humans , Hedgehog Proteins , Minocycline , Doxycycline/pharmacology , Tetracycline , Osteogenesis , Anti-Bacterial Agents/pharmacology , Immunologic Factors
18.
J Funct Biomater ; 14(9)2023 Sep 08.
Article in English | MEDLINE | ID: mdl-37754877

ABSTRACT

This research investigates pH changes during the green synthesis of ZnO nanoparticles (NPs) and emphasises its importance in their physicochemical, antibacterial, and biological properties. Varying the synthesis pH from 8 to 12 using "Bravo de Esmolfe" apple extracts neither affected the morphology nor crystallinity of ZnO but impacted NP phytochemical loads. This difference is because alkaline hydrolysis of phytochemicals occurred with increasing pH, resulting in BE-ZnO with distinct phytocargos. To determine the toxicity of BE-ZnO NPs, Galleria mellonella was used as an alternative to non-rodent models. These assays showed no adverse effects on larvae up to a concentration of 200 mg/kg and that NPs excess was relieved by faeces and silk fibres. This was evaluated by utilising fluorescence-lifetime imaging microscopy (FLIM) to track NPs' intrinsic fluorescence. The antibacterial efficacy against Staphylococcus aureus was higher for BE-ZnO12 than for BE-ZnO8; however, a different trend was attained in an in vivo infection model. This result may be related to NPs' residence in larvae haemocytes, modulated by their phytocargos. This research demonstrates, for the first time, the potential of green synthesis to modulate the biosafety and antibacterial activity of NPs in an advanced G. mellonella infection model. These findings support future strategies to overcome antimicrobial resistance by utilizing distinct phytocargos to modulate NPs' action over time.

19.
Psychooncology ; 32(11): 1702-1709, 2023 11.
Article in English | MEDLINE | ID: mdl-37749768

ABSTRACT

BACKGROUND: The first medical oncology appointment serves as a platform for patients to comprehend their diagnosis and prognostic implications of cancer. This study aimed to determine patients' communication preferences during their first medical oncology appointment and to assess the disparities between patients' preferences and perceptions. METHODS: A total of 169 cancer patients participated by completing the Communication in First Medical Oncology Appointment Questionnaire (C-FAQ), a two-section questionnaire designed to assess patients' preferences and perceptions regarding Content (information provided and its extent), Facilitation (timing and location of information delivery), and Support (emotional support) during their first medical oncology appointment. A comparative analysis was conducted to assess the variations between preferences and perceptions. RESULTS: Content emerged as the most significant dimension compared to Facilitation and Support. The physician's knowledge, honesty, and ability to provide clear information were considered the most important attributes. Patients evaluated most of their preferences as "very important". Patients' perception of the communication dimensions present during their appointment was below preferences for 11 items, indicating significant discrepancies in clinical practice. CONCLUSIONS: Patients highly valued their preferences concerning Content, Facilitation, and Support dimensions of communication. However, patient preferences were more prominently oriented towards the Content dimension. The discrepancies between preferences and perceptions should be viewed as an opportunity for enhancing communication skills through training.


Subject(s)
Neoplasms , Physician-Patient Relations , Humans , Neoplasms/psychology , Medical Oncology , Communication , Patient Preference/psychology
20.
J Sports Sci Med ; 22(3): 417-424, 2023 09.
Article in English | MEDLINE | ID: mdl-37711703

ABSTRACT

The aim of the present study was two-fold: (i) to analyze the progression and variability of swimming performance (from entry times to best performances) in the 50, 100, and 200 m at the most recent FINA World Championships and (ii) to compare the performance of the Top16, semifinalists, and finalists between all rounds. Swimmers who qualified with the FINA A and B standards for the Budapest 2022 World Championships were considered. A total of 1102 individual performances swimmers were analyzed in freestyle, backstroke, breaststroke, and butterfly events. The data was retrieved from the official open-access websites of OMEGA and FINA. Wilcoxon test was used to compare swimmers' entry times and best performances. Repeated measures ANOVA followed by the Bonferroni post-hoc test were performed to analyze the round-to-round progression. The percentage of improvement and variation in the swimmers' performance was computed between rounds. A negative progression (entry times better than best performance) and a high variability (> 0.69%) were found for most events. The finalists showed a positive progression with a greater improvement (~1%) from the heats to the semifinals. However, the performance progression remained unchanged between the semifinals and finals. The variability tended to decrease between rounds making each round more homogeneous. Coaches and swimmers can use these indicators to prepare a race strategy between rounds.


Subject(s)
Hot Temperature , Swimming , Humans
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