The Influence of the Diameter of Orthodontic Mini-Implants on Primary Stability: Bending Tests-An In Vitro Study.

Orthodontic Mini-Implants have a high success rate, but it is crucial to assess the load that they bear in order to maintain their primary stability. Increasing the diameter can improve this stability, but there are limitations due to the proximity of the tooth roots. To avoid damage, smaller diameters are used, which can decrease resistance and cause permanent deformations. OBJECTIVE: The objective of this study is to evaluate the influence of the diameter of Mini-Implants through bending force tests, taking into account primary stability after one and two insertions. METHODS: Here, 40 Ti6AI4V alloy Mini-Implants of two different brands and diameters were divided into eight groups, half of which received one insertion in the artificial bone, and the rest received two. All were subjected to a constant bending force using an INSTRON-Electropuls E10000LT (Norwood, MA, USA) until fracture. RESULTS: The smaller-diameter Mini-Implants were less resistant to fracture, but both were able to withstand the necessary loads produced by orthodontic movements. As for the inserts, there were no statistically significant differences. CONCLUSIONS: There is an advantage to using 1.6 mm Mini-Implants over 2.0 mm ones, as a smaller diameter does not lead to fracture due to the forces used in orthodontic treatment. Having one or two inserts did not have a statistically significant effect.

Understanding the Kinematic Profile of 2 Underwater Pullout Breaststroke Techniques.

PURPOSE: To compare the kinematic profile of 2 underwater pullout breaststroke techniques. METHODS: Sixteen swimmers (9 men, 20.67 [2.71] y old; 7 women, 18.86 [0.83] y old) performed 3 × 25-m breaststroke using 2 pullout breaststroke techniques: Fly-Kick first and Combined. A speedometer was used to assess the peak and the mean velocity during the glide, propulsion, and recovery phases of both techniques, as well as for the total underwater sequence. The underwater distance was retrieved from video footage and was considered for each pullout technique. The range of motion of the knee during the fly-kick was also retrieved, and the time to complete the 25 m was considered the performance outcome, accompanied by the mean velocity, stroke rate, stroke length, and stroke index. RESULTS: Velocity-time series showed different profiles between pullout techniques (P ≤ .05) mostly in the glide and propulsion phases for males and females, respectively. The mean velocity of 25 m was shown to be greater in females when using the Fly-Kick first technique (P = .05, d = 0.36). Greater values in total underwater distance and knee range of motion were also observed for this technique in both cohorts. Conclusions: Female swimmers presented a higher performance when using the Fly-Kick first technique. Different kinematic profiles arise when swimmers use different underwater pullout techniques where the Fly-Kick first may allow them to reach higher kinematical standard.

Taking climate-smart governance to the high seas.

Comprehensive spatial planning in international waters is key to achieving ocean sustainability.

Case report: Primary CDK4/6 inhibitor and endocrine therapy in locally advanced breast cancer and its effect on gut and intratumoral microbiota.

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.

Home Ultrasound: A Contemporary and Valuable Tool for Palliative Medicine.

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.

Hematopoietic stem cell gene editing rescues B-cell development in X-linked agammaglobulinemia.

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.

Standard Doses of Cholecalciferol Reduce Glucose and Increase Glutamine in Obesity-Related Hypertension: Results of a Randomized Trial.

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.

Study protocol for a randomized controlled trial testing the efficacy of Emotion Detectives In-Out: a blended version of the unified protocol for transdiagnostic treatment of emotional disorders in Portuguese children.

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).

Tryptase in Acute Appendicitis: Unveiling Allergic Connections through Compelling Evidence.

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.

Nonlinear Analysis of the Hand and Foot Force-Time Profiles in the Four Competitive Swimming Strokes.

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.

Investigating Cox-2 and EGFR as Biomarkers in Canine Oral Squamous Cell Carcinoma: Implications for Diagnosis and Therapy.

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.

Reviewing particulate delivery systems loaded with repurposed tetracyclines - From micro to nanoparticles.

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.

A Rare Case of a Chylous Pleural Effusion as the Initial Manifestation of Synchronous Tumors.

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.

Ectopic Intrathyroidal Parathyroid Adenoma Presenting With Osteoporotic Fractures in a Young Man: A Case Report.

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.

A comparison of load cell and pressure sensors to measure in-water force in young competitive swimmers.

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.

Some new insights into the biological activities of carboxymethylated polysaccharides from Lasiodiplodia theobromae.

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.

Long-term locoregional recurrence in patients treated for breast cancer.

BACKGROUND/PURPOSE: Locoregional control in breast cancer is a fundamental part of treatment and determinant for survival outcomes. It has been reported that most locoregional recurrence (LRR) events occur in the first 5 years after treatment. However, LRR continue to occur after this timeline, with unclear risk factors and unknown survival impact. METHODS: Retrospective singe-centered cohort of patients treated for primary breast cancer, between January 2002 and December 2004. Primary outcome was LRR; secondary outcomes were overall survival (OS), disease-free survival (DFS), and predictive factors for LRR. RESULTS: This analysis included 1001 patients, of which 959 (95%) had invasive carcinoma. A mastectomy was performed in 501 (50%) and 500 (50%) had breast conservative surgery (BCS). Median follow-up time was 197 [Inter-quartile range (IQR) 96-211] months. Global LRR rate was 7.6%, with median time to recurrence of 45 [IQR 21-91] months. There was no difference in LRR rate after mastectomy vs BCS, adjusted to tumor stage (p > 0.05). The 10-year OS and DFS rates were 68.4 and 77.8%, respectively. Factors associated with LRR were metastatic axillary lymph nodes and high histologic grade (p < 0.05). Estrogen-negative (ER) tumors had higher LRR rates than ER-positive tumors in the first 5 years (p < 0.05); but no difference was observed with longer follow-up (p > 0.05). LRR was associated with OS (p < 0.05). DISCUSSION AND CONCLUSIONS: Global LRR in this cohort was 7.6% (with over 16 years of follow-up). LRR associates with decreased OS. Time to LRR varies significantly with tumor biology, supporting differentiation of follow-up regimens.

Frequency of CDH1, CTNNA1 and CTNND1 Germline Variants in Families with Diffuse and Mixed Gastric Cancer.

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.