Unveiling the comorbidity burden of male breast cancer.

Male breast cancer (MBC) is a rare condition with unique characteristics compared to female breast cancer (FBC). Despite its scarceness, there is growing evidence that MBC should not be studied and treated as FBC due to factors like later diagnosis stage and distinct genetic makeup. Retrospective observational study in the EpiChron Cohort, selecting all the prevalent patients with breast cancer between 2010 and 2019. Logistic models were used to determine associated comorbidities. Between 2010 and 2019, 105 MBC and 11,657 FBC patients were found in the EpiChron Cohort. MBC patients had a high mean age at diagnosis and number of comorbidities. Paying attention to comorbidity prevalences in breast cancer patients, it was clear that MBC patients tended to be prone to cardio-metabolic coexisting diseases, while FBC patients were more prone to hormone-, bone- and mental diseases. There were nine chronic conditions associated to MBC patients, but after a year-by-birth matching only four associations remained. Two of them were associated previously [odds ratio (95% confidence interval)]: "Disorder of lipid metabolism" [1.65 (1.03-2.64)] and "Genitourinary symptoms and ill-defined conditions" [2.03 (1.07-3.87)]; and the other two were new, "Anxiety disorders" [2.05 (1.09-3.87)] and "Osteoporosis" [3.58 (1.26-10.14)]. After comparing associated comorbidities in FBC with those in MBC, it seems MBC patients share some of them, but they have their own particular set of coexisting diseases. In fact, once a year-by-birth matching was performed in MBC patient cohort, it was more obvious MBC comorbidities behave more similar to none-Breast-Cancer male population than to FBC patients. These findings highlight the distinct characteristics of the MBC patient population and the need for a tailored approach of managing MBC.

Impact of Remnant Cholesterol on Cardiovascular Risk in Diabetes.

PURPOSE OF REVIEW: Individuals with diabetes face increased risk of atherosclerotic cardiovascular disease (ASCVD), in part due to hyperlipidemia. Even after LDL cholesterol-lowering, residual ASCVD risk persists, part of which may be attributed to elevated remnant cholesterol. We describe the impact of elevated remnant cholesterol on ASCVD risk in diabetes. RECENT FINDINGS: Preclinical, observational, and Mendelian randomization studies robustly suggest that elevated remnant cholesterol causally increases risk of ASCVD, suggesting remnant cholesterol could be a treatment target. However, the results of recent clinical trials of omega-3 fatty acids and fibrates, which lower levels of remnant cholesterol in individuals with diabetes, are conflicting in terms of ASCVD prevention. This is likely partly due to neutral effects of these drugs on the total level of apolipoprotein B(apoB)-containing lipoproteins. Elevated remnant cholesterol remains a likely cause of ASCVD in diabetes. Remnant cholesterol-lowering therapies should also lower apoB levels to reduce risk of ASCVD.

A systematic review of the claw toe deformity: What is known and what is needed apart from surgical procedures.

The claw toe deformity is a painful condition that mainly affects the adult population. Although there are many different treatments to solve the deformity, there is no optimal procedure to restore the normal foot mechanics. The objective of this review was to identify the technical features of the kinematic evaluation methods used in patients with claw toes. Furthermore, the aim of this review was to clarify what is known and what is needed apart from the surgical procedures to correct the claw toe deformity, with the purpose of reducing risk factors of falling in elderly people. A search in electronic databases, such as Scopus (n = 78), Google Scholar (n = 705) and ScienceDirect (n = 290) was conducted. There were seven articles (43.75%) related to the fixation (arthrodesis) of proximal and distal interphalangeal joints, one article (6.25%) describes the correction of the claw toe through plantar plate tenodesis and release of collateral ligaments, four articles (25%) describe the procedure of tendon transfer, one article (6.25%) describes flexor digitorum brevis tenotomy and a proximal interphalangeal joint arthrolysis, and another article (6.25%) presented the impact of partial phalanx osteotomy to treat the claw toe deformity. In conclusion, the review indicates that there are several studies related to the treatment or correction of claw toe deformity. However, there is a lack of knowledge of the postsurgical effects of treating claw toe condition, especially in the structural mechanics (plantar pressure distribution, stability, gait, foot mechanics and so on) of the foot after the correction of the claw toe deformity. The analysis of the foot mechanics after the correction of the claw toes has to be paramount to determine the benefits of the correction.

The DEBBRAH trial: Trastuzumab deruxtecan in HER2-positive and HER2-low breast cancer patients with leptomeningeal carcinomatosis.

BACKGROUND: Leptomeningeal disease (LMD) is associated with poor survival and diminished quality of life. Trastuzumab deruxtecan (T-DXd) has shown remarkable intracranial and extracranial activity in human epidermal growth factor receptor 2 (HER2)-positive and HER2-low advanced breast cancer (ABC). The DEBBRAH trial was designed to evaluate its efficacy and safety in patients with HER2-positive and HER2-low ABC with a history of brain metastases (BMs) and/or LMD. Here, we report results from cohort 5, which specifically included patients with pathologically confirmed LMD. METHODS: This single-arm, open-label, five-cohort, phase 2 trial enrolled seven patients in cohort 5 who received 5.4 mg/kg T-DXd intravenously every 21 days until disease progression or unacceptable toxicity. The primary endpoint was overall survival (OS). Key secondary endpoints included progression-free survival (PFS) and safety profile. FINDINGS: At data cutoff (April 4, 2023), the median duration of follow-up was 12.0 months (range, 2.5-18.6). The median OS was 13.3 months (95% confidence interval [CI], 5.7-NA, p < 0.001), meeting the primary endpoint. The median PFS was 8.9 months (95% CI, 2.1-NA). Two (28.6%) of seven patients remained on treatment after 18.6 and 11.9 months, respectively. Of the five patients who progressed and died, none had intracranial progression or clinical worsening of leptomeningeal symptoms. Notably, 71.4% (95% CI, 29.0-96.3) achieved prolonged stabilization (≥24 weeks) by response evaluation criteria in solid tumors (RECIST) v.1.1. No unexpected safety signals and no treatment-related deaths were observed. CONCLUSIONS: T-DXd showed promising antitumor activity in patients with HER2-positive and HER2-low ABC with previously untreated, pathologically confirmed LMD. These encouraging data warrant further investigation to address the unmet need in this difficult-to-treat condition. FUNDING: This work was funded by Daiichi Sankyo/AstraZeneca. This trial is registered with ClinicalTrials.gov: NCT04420598.

Male breast cancer: A multicenter study in Aragon over 27 years.

INTRODUCTION: Male breast cancer accounts for 1% of all breast cancers. Its low frequency leads to a lack of awareness, resulting in significant diagnostic delays. Additionally, this limits the available evidence, which primarily uses diagnostic-therapeutic algorithms based on women. OBJECTIVES: To analyze the prevalence, clinical presentation, anatomical and pathological characteristics, and prognosis of male breast cancer using one of the largest series available. Secondarily, to compare our data with studies conducted in women. MATERIALS AND METHODS: A multicenter, observational, descriptive, retrospective study was conducted in the autonomous community of Aragon, Spain, from 1995 to 2022 including men with a pathological diagnosis of breast cancer. RESULTS: A total of 148 patients were included, with a prevalence of 1%. The most common clinical presentation was a palpable retroareolar mass. Invasive ductal carcinoma was the most frequent type (88.89%), and luminal B was the predominant subtype (47.76%). Surgery was the most utilized treatment; mastectomy was performed in 90.34% and AL in 46.89%. At diagnosis, 52.46% had extramammary involvement. The recurrence rate was 24.1%, and the mortality attributed to the disease was 14.6%. CONCLUSIONS: There is a high rate of metastatic involvement at diagnosis, a high percentage of mutilating surgeries, and a high number of recurrences compared to available studies on males. Additionally, a worse prognosis is observed compared to breast cancer in women, despite these tumors having a less aggressive molecular subtype. These findings highlight the importance of conducting studies focused on men to develop specific protocols.

Light-induced magnetization from magnonic rectification.

Rectification describes the conversion of an oscillating field or current into a quasi-static one and the most basic example of a rectifier is an AC/DC converter in electronics. This principle can be translated to nonlinear light-matter interactions, where optical rectification converts the oscillating electric field component of light into a quasi-static polarization and phononic rectification converts a lattice vibration into a quasi-static structural distortion. Here, we present a rectification mechanism for magnetism that we call magnonic rectification, where a spin precession is converted into a quasi-static magnetization through the force exerted by a coupled chiral phonon mode. The transiently induced magnetic state resembles that of a canted antiferromagnet, opening an avenue toward creating dynamical spin configurations that are not accessible in equilibrium.

Influence of the kinesiophobia and its pain intensity relationship in subjects with onychocryptosis.

Background: Onychocryptosis is a nail deformity that occurs when the side of the nail grows into soft tissue, which causes pain, sepsis and the formation of granulation. The aim of the study was to evaluate and compare different levels of kinesiophobia in subjects with onychocryptosis before and after surgery to eliminate this condition. Methods: A descriptive and observational study was conducted with a total sample size of 25 subjects with a mean age of 40.96 ± 18.25 years. The pretest sample was composed of the 25 subjects before the surgical treatment of onychocryptosis and the posttest sample was composed of the same 25 subjects after the surgical treatment of onychocryptosis. Kinesiophobia levels and total scores were self-reported using the Spanish version of the Tampa Scale for Kinesiophobia (TSK-11). Results: The Wilcoxon test for related samples and the Mann-Whitney U test for independent samples were used to compare the results before and after the surgical treatment. It was observed that in all the items as well as in the total score, there were significant changes in the levels of kinesiophobia, after the surgical intervention for onychocryptosis (P < 0.05) compared to the levels before surgery, except for items 4 and 11 in which there were no significant differences (P > 0.05). Before surgery, 0% of the subjects with onychocryptosis reported not being afraid of movement, 16% reported mild fear of movement, 8% reported moderate fear of movement and 76% of the subjects with onychocryptosis reported severe and maximum fear of movement. On the other hand, 100% of the subjects did not report kinesiophobia after surgical treatment (P < 0.01). Conclusions: The levels of kinesiophobia were higher in the subjects with onychocryptosis compared to the subjects after having undergone surgery to eliminate onychocryptosis.

HIV Symptom Clusters Among Sexual Minority Men in Ghana, West Africa: A Cross-sectional Study.

ABSTRACT: The aims of this study were to determine if HIV symptoms among sexual minority men formed clusters and to examine the sociodemographic and clinical characteristics that are associated with these clusters. We analyzed cross-sectional data from Ghanaian sexual minority men (N = 225) living with HIV. We used both principal component analysis and multivariable linear regression. Our findings indicate that sadness (64.0%) and headache (62.7%) were the most prevalent symptoms among our sample. Seven symptom clusters were identified: neurological symptoms, psychological symptoms, gastrointestinal symptoms, dermatological symptoms, self-concept/self-esteem, weight/diet-related symptoms, and sleepquality and potential disturbances. Late HIV diagnosis was significantly associated with higher distress scores for all symptom clusters except for the self-concept/self-esteem and gastrointestinal symptoms clusters. The findings emphasize the importance of early HIV symptom identification.

Influence of the biomechanical evaluation of rupture using two shapes of same intramedullary implant after proximal interphalangeal joint arthrodesis to correct the claw/hammer pathology: A finite element study.

We used finite element analysis to study the mechanical stress distribution of a new intramedullary implant used for proximal interphalangeal joint (PIPJ) arthrodesis (PIPJA) to surgically correct the claw-hammer toe deformity that affects 20% of the population. After geometric reconstruction of the foot skeleton from claw toe images of a 36-year-old male patient, two implants were positioned, in the virtual model, one neutral implant (NI) and another one 10° angled (10°AI) within the PIPJ of the second through fourth HT during the toe-off phase of gait and results were compared to those derived for the non-surgical foot (NSF). A PIPJA was performed on the second toe using a NI reduced tensile stress at the proximal phalanx (PP) (45.83 MPa) compared to the NSF (59.44 MPa; p < 0.001). When using the 10°AI, the tensile stress was much higher at PP and middle phalanges (MP) of the same toe, measuring 147.58 and 160.58 MPa, respectively, versus 59.44 and 74.95 MPa at corresponding joints in the NSF (all p < 0.001). Similar results were found for compressive stresses. The NI reduced compressive stress at the second PP (-65.12 MPa) compared to the NSF (-113.23 MPa) and the 10°AI (-142 MPa) (all p < 0.001). The von Mises stresses within the implant were also significantly lower when using NI versus 10°AI (p < 0.001). Therefore, we do not recommend performing a PIPJA using the 10°AI due to the increase in stress concentration primarily at the second PP and MP, which could promote implant breakage.

Shared germline genomic variants in two patients with double primary gastrointestinal stromal tumours (GISTs).

BACKGROUND: Gastrointestinal stromal tumours (GISTs) are prevalent mesenchymal tumours of the gastrointestinal tract, commonly exhibiting structural variations in KIT and PDGFRA genes. While the mutational profiling of somatic tumours is well described, the genes behind the susceptibility to develop GIST are not yet fully discovered. This study explores the genomic landscape of two primary GIST cases, aiming to identify shared germline pathogenic variants and shed light on potential key players in tumourigenesis. METHODS: Two patients with distinct genotypically and phenotypically GISTs underwent germline whole genome sequencing. CNV and single nucleotide variant (SNV) analyses were performed. RESULTS: Both patients harbouring low-risk GISTs with different mutations (PDGFRA and KIT) shared homozygous germline pathogenic deletions in both CFHR1 and CFHR3 genes. CNV analysis revealed additional shared pathogenic deletions in other genes such as SLC25A24. No particular pathogenic SNV shared by both patients was detected. CONCLUSION: Our study provides new insights into germline variants that can be associated with the development of GISTs, namely, CFHR1 and CFHR3 deep deletions. Further functional validation is warranted to elucidate the precise contributions of identified germline mutations in GIST development.

Do Ethnic Identity, Familial, and Community Contexts Impact the Association Between Adverse Childhood Experiences and Psychopathology Among Latinx Adolescents?

OBJECTIVE: Few studies have explored the interplay of how individual identity, parental, familial, and contextual factors impact associations between Latinx adolescent adversities and psychopathology. This study aimed to examine whether these factors mediate the relationship between adversities and psychopathology in Latinx youth. METHOD: Latinx youth (n = 2,411) data from the Adolescent Brain Cognitive Development (ABCD) Study were used to examine path models with adverse childhood experiences (ACEs) as the predictor and either youth- or caregiver-rated internalizing/externalizing scores over 4 timepoints as the outcome (ages 9-13 years). Models examined 3 potential mediators: (1) ethnic identity, (2) familial context (comprising parental monitoring, family conflict, and caregiver acceptance), and (3) community cohesion. Models were conducted separately for internalizing and externalizing symptoms. RESULTS: Greater adversity was associated with greater youth- and caregiver-rated internalizing/externalizing psychopathology over time. Greater adversity was associated with lower family functioning and lower ethnic identity, and greater family functioning was associated with lower psychopathology. Family functioning mediated associations between adversity and psychopathology over time (youth-reported internalizing: 95% CI = 0.012-0.019; youth-reported externalizing: 95% CI = 0.020-0.028). In contrast, there was not strong evidence for ethnic identity and community cohesion mediating associations between adversities and psychopathology over time. CONCLUSION: Unlike previous studies, ethnic identity did not influence the relationship between ACEs and psychopathology over time. Additional research is needed to identify whether possible tensions rise as Latinx youth acculturate into US culture and achieve optimal levels of ethnic identity formation. Providers need to assess specific Latinx parental and familial contexts that may interfere with youth identity formation.

Contribution of the abbreviated CAVE-st questionnaire in Spanish: the attitudes toward childbirth experiences.

There are several factors that influence women's childbirth experience, and personal interactions with health professionals are of particular significance. The main objective of this study was to present the validation of an abbreviated form of an existing questionnaire on attitudes about childbirth in medical and nursing students. We used a sample of 512 perinatal medicine and nursing students who received the original 52-item CAVE-st questionnaire to obtain a shorter version with proper psychometric properties. We used Cronbach's alpha coefficient to evaluate the new version's internal consistency. The Kaiser- Meyer-Olkin test and the Barlett sphericity test were performed to assess the suitability of exploratory factor analysis (EFA). Subsequently, confirmatory factor analysis (CFA) was performed using structural equation models in a second sample of 139 medical students. We obtained a 15-item version with a Cronbach's alpha of 0.82. The EFA revealed a four-dimensional structure, similar to the full 52-item version. In the CFA the adjustment indexes showed good model fitness, RMSEA= 0.046 [CI 0.00-0.07]; CFI = 0.978. We can conclude that the 15-item version is a valid tool for evaluating the attitude of students toward childbirth, pointing out the matters that should be improved in their training to avoid obstetric trauma by the promotion of a positive experience in women during childbirth.

Short-term outcomes of dogs and cats undergoing lung lobectomy using either a self-ligating loop or a thoracoabdominal stapler.

OBJECTIVE: To assess clinical outcomes of lung lobectomies in dogs and cats using either self-ligating loops (SLLs) or thoracoabdominal (TA) staplers, aiming to inform sample size calculations for future superiority trials. STUDY DESIGN: Retrospective study. ANIMALS: A total of 72 dogs and 15 cats. METHODS: Records from January 2003 to October 2023 at a single institution were reviewed. Cases with lung lobectomy performed via TA stapler or SLL with a minimum 14-day postoperative follow-up were included. Pre-, intra-, and postoperative data were collected, with outcomes of interest including the frequency of intra- and postoperative complications. Outcome comparisons between techniques were performed to inform sample size calculations. RESULTS: A total of 101 lung lobectomies were performed. The TA stapler was used in 83 (82.2%) and the SLL in 18 (17.8%) lung lobectomies. Intraoperative complications were identified in 14/101 lung lobectomies (13.9%), including intraoperative hemorrhage in 12/101 lobectomies (11.8%) and air leakage in 2/101 lobectomies (1.9%). Postoperative complications were identified in 12/87 cases (13.8%), including 4 (4.6%) catastrophic complications and 5 (5.8%) major complications. All intra- and postoperative complications occurred in cases having undergone stapled lung lobectomy; however, no differences were identified between surgical technique and either intraoperative (p = .069) or postoperative complications (p = .112). A sample size of 103 lobectomies per technique group would be required for appropriate evaluation. CONCLUSION: Lung lobectomy using either surgical technique provided a good short-term outcome in this population. CLINICAL SIGNIFICANCE: Self-ligating loop lung lobectomy provided a comparable alternative to stapled lung lobectomy. Further studies are needed to assess technique superiority.

Polymerase Chain Reaction and Dot-Blot Hybridization for Leptospira Detection in Water Samples.

The dot-blot is a simple, fast, sensitive, and versatile technique that enables the identification of minimal quantities of DNA specifically targeted by probe hybridization in the presence of carrier DNA. It is based on the transfer of a known amount of DNA onto an inert solid support, such as a nylon membrane, utilizing the dot-blot apparatus and without electrophoretic separation. Nylon membranes have the advantage of high nucleic acid binding capacity (400 µg/cm2), high strength, and are positively or neutrally charged. The probe used is a highly specific ssDNA fragment of 18 to 20 bases long labeled with digoxigenin (DIG). The probe will conjugate with the Leptospira DNA. Once the probe has hybridized with the target DNA, it is detected by an anti-digoxigenin antibody, allowing its easy detection through its emissions revealed in an X-ray film. The dots with an emission will correspond to the DNA fragments of interest. This method employs the non-isotopic labeling of the probe, which may have a very long half-life. The drawback of this standard immuno-label is a lower sensitivity than isotopic probes. Nevertheless, it is mitigated by coupling polymerase chain reaction (PCR) and dot-blot assays. This approach enables the enrichment of the target sequence and its detection. Additionally, it may be used as a quantitative application when compared against a serial dilution of a well-known standard. A dot-blot application to detect Leptospira from the three main clades in water samples is presented here. This methodology can be applied to large amounts of water once they have been concentrated by centrifugation to provide evidence of the presence of Leptospiral DNA. This is a valuable and satisfactory tool for general screening purposes, and may be used for other non-culturable bacteria that may be present in water, enhancing the comprehension of the ecosystem.

Biological maturity vs. relative age: Independent impact on physical performance in male and female youth handball players.

Maturity status and relative age are two of the determining factors in talent development. The aim of the study was to analyze the influence of biological maturity status and relative age on physical performance in young male and female handball players. The sample included 48 males (14.11 ± 1.17 years) and 41 females (14.25 ± 1.64 years) players from one Spanish professional handball academy. Anthropometric data (height, sitting height, body mass and self-reported biological parent heights) and physical performance data (CMJ, DJ, 20 m speed, T-test and throwing velocity) were collected. Biological maturity status was determined as the percentage of predicted adult height, while relative age was estimated in birth quartiles based on biennial age grouping (Q1-Q8). The results showed a positive correlation between maturity status and CMJ in male players (p < 0.01). Differences in CMJ performance according to maturity status were identified (p < 0.05), with higher jump heights being recorded especially in early maturing boys (p < 0.01) and first lines and wings (p < 0.05). The variance in CMJ test scores could be explained by the maturity status by 42.90% in U-15 (p < 0.05) and 72.60% in U-16 male players (p < 0.001). By contrast, no differences were found in girls (p > 0.05). Moreover, no relationships were found between relative age and indices of physical performance (p > 0.05). Overall, maturity status had greater impacts on the tests of physical performance than relative age. Stakeholders should monitor the maturity status of young handball players to avoid physical performance biases that do not allow them to develop their sporting potential.

Flotillin-mediated stabilization of unfolded proteins in bacterial membrane microdomains.

The function of many bacterial processes depends on the formation of functional membrane microdomains (FMMs), which resemble the lipid rafts of eukaryotic cells. However, the mechanism and the biological function of these membrane microdomains remain unclear. Here, we show that FMMs in the pathogen methicillin-resistant Staphylococcus aureus (MRSA) are dedicated to confining and stabilizing proteins unfolded due to cellular stress. The FMM scaffold protein flotillin forms a clamp-shaped oligomer that holds unfolded proteins, stabilizing them and favoring their correct folding. This process does not impose a direct energy cost on the cell and is crucial to survival of ATP-depleted bacteria, and thus to pathogenesis. Consequently, FMM disassembling causes the accumulation of unfolded proteins, which compromise MRSA viability during infection and cause penicillin re-sensitization due to PBP2a unfolding. Thus, our results indicate that FMMs mediate ATP-independent stabilization of unfolded proteins, which is essential for bacterial viability during infection.

Transparency and Reproducibility in the Adolescent Brain Cognitive Development (ABCD) Study.

Background: Transparency can build trust in the scientific process, but scientific findings can be undermined by poor and obscure data use and reporting practices. The purpose of this work is to report how data from the Adolescent Brain Cognitive Development (ABCD) Study has been used to date, and to provide practical recommendations on how to improve the transparency and reproducibility of findings. Methods: Articles published from 2017 to 2023 that used ABCD Study data were reviewed using more than 30 data extraction items to gather information on data use practices. Total frequencies were reported for each extraction item, along with computation of a Level of Completeness (LOC) score that represented overall endorsement of extraction items. Univariate linear regression models were used to examine the correlation between LOC scores and individual extraction items. Post hoc analysis included examination of whether LOC scores were correlated with the logged 2-year journal impact factor. Results: There were 549 full-length articles included in the main analysis. Analytic scripts were shared in 30% of full-length articles. The number of participants excluded due to missing data was reported in 60% of articles, and information on missing data for individual variables (e.g., household income) was provided in 38% of articles. A table describing the analytic sample was included in 83% of articles. A race and/or ethnicity variable was included in 78% of reviewed articles, while its inclusion was justified in only 41% of these articles. LOC scores were highly correlated with extraction items related to examination of missing data. A bottom 10% of LOC score was significantly correlated with a lower logged journal impact factor when compared to the top 10% of LOC scores (ß=-0.77, 95% -1.02, -0.51; p-value < 0.0001). Conclusion: These findings highlight opportunities for improvement in future papers using ABCD Study data to readily adapt analytic practices for better transparency and reproducibility efforts. A list of recommendations is provided to facilitate adherence in future research.