The Effect of Exercise on Reducing Lymphedema Severity in Breast Cancer Survivors.

Exercise has been repeatedly shown to be safe and beneficial for cancer survivors. However, there is no normative guideline for exercise prescription, and it is still under exploration. Therefore, this literature review aims to provide some advice for the formulation of exercise prescriptions for patients with breast cancer-related lymphedema (BCRL) from the perspective of reducing lymphedema severity. A review of relevant studies published before November 2023 was conducted using three scientific databases: PubMed, Embase, and Scopus. A total of 2696 articles were found. Eventually, 13 studies fulfilled the inclusion criteria and were included in this literature review. We concluded that daily, or nearly daily, exercise at home can be recommended. Moreover, reduced lymphedema severity may not be maintained after ceasing the exercise program, so exercise should be a lifelong practice.

Epidemiological characteristics of human infections with avian influenza A(H5N6) virus, China and Laos: A multiple case descriptive analysis, February 2014-June 2023.

Background: The first human infection with highly pathogenic avian influenza A(H5N6) virus was reported in 2014. From then until June 30, 2023, 85 human cases with confirmed A(H5N6) infection have been reported worldwide. Objective: To address the present gap in knowledge of the overall epidemiology of human A(H5N6) infections, the epidemiological characteristics of human infection with A(H5N6) in China from February 2014 to June 2023 are described. Methods: Considering the severity of human infections with A(H5N6) virus (case fatality rate: 39%), the increased frequency of case reports from 2021 to present day, and lack of comprehensive epidemiologic analysis of all cases, we conducted a multiple-case descriptive analysis and a literature review to create an epidemiologic profile of reported human cases. Case data was obtained via a literature search and using official intelligence sources captured by the Public Health Agency of Canada's International Monitoring and Assessment Tool (IMAT), including Event Information Site posts from the World Health Organization. Results: Most human A(H5N6) cases have been reported from China (China: 84; Laos: 1), with severe health outcomes, including hospitalization and death, reported among at-risk populations. The majority (84%) of cases reported contact with birds prior to illness onset. Cases were detected throughout the course of the year, with a slight decrease in illness incidence in the warmer months. Conclusion: As A(H5N6) continues to circulate and cause severe illness, surveillance and prompt information sharing is important for creating and implementing effective public health measures to reduce the likelihood of additional human infections.

Revisiting the role of behavior-mediated structuring in the survival of populations in hostile environments.

Increasing the population density of target species is a major goal of ecosystem and agricultural management. This task is especially challenging in hazardous environments with a high abundance of natural enemies such as parasites and predators. Safe locations with lower mortality have been long considered a beneficial factor in enhancing population survival, being a promising tool in commercial fish farming and restoration of threatened species. Here we challenge this opinion and revisit the role of behavior structuring in a hostile environment in shaping the population density. We build a mathematical model, where individuals are structured according to their defensive tactics against natural enemies. The model predicts that although each safe zone enhances the survival of an individual, for an insufficient number of such zones, the entire population experiences a greater overall mortality. This is a result of the interplay of emergent dynamical behavioral structuring and strong intraspecific competition for safe zones. Non-plastic structuring in individuals' boldness reduces the mentioned negative effects. We demonstrate emergence of non-plastic behavioral structuring: the evolutionary branching of a monomorphic population into a dimorphic one with bold/shy strains. We apply our modelling approach to explore fish farming of salmonids in an environment infected by trematode parasites.

Survival outcomes and predicting intracranial metastasis in stage III non-small cell lung cancer treated with definitive chemoradiation: Real-world data from a tertiary cancer center.

PURPOSE/OBJECTIVE: Around 30% of patients with non-small cell lung cancers (NSCLC) are diagnosed with stage III disease at presentation, of which about 50% are treated with definitive chemoradiation (CRT). Around 65-80% of patients will eventually develop intracranial metastases (IM), though associated risk factors are not clearly described. We report survival outcomes and risk factors for development of IM in a cohort of patients with stage III NSCLC treated with CRT at a tertiary cancer center. MATERIALS/METHODS: We identified 195 patients with stage III NSCLC treated with CRT from January 2010 to May 2021. Multivariable logistic regression was used to generate odds ratios for covariates associated with development of IM. Kaplan-Meier analysis with the Log Rank test was used for unadjusted time-to-event analyses. P-value for statistical significance was set at < 0.05 with a two-sided test. RESULTS: Out of 195 patients, 108 (55.4%) had stage IIIA disease and 103 (52.8%) had adenocarcinoma histology. The median age and follow-up (in months) was 67 (IQR 60-74) and 21 (IQR 12-43), respectively. The dose of radiation was 60 Gy in 30 fractions for148 patients (75.9%). Of the 77 patients who received treatment since immunotherapy was available and standard at our cancer center, 45 (58.4%) received at least one cycle. During follow-up, 84 patients (43.1%) developed any metastasis, and 33 (16.9%) developed IM (either alone or with extracranial metastasis). 150 patients (76.9%) experienced a treatment delay (interval between diagnosis and treatment > 4 weeks). Factors associated with developing any metastasis included higher overall stage at diagnosis (p = 0.013) and higher prescribed dose (p = 0.022). Factors associated with developing IM included higher ratio of involved over sampled lymph nodes (p = 0.001) and receipt of pre-CRT systemic or radiotherapy for any reason (p = 0.034). On multivariate logistical regression, treatment delay (OR 3.9, p = 0.036) and overall stage at diagnosis (IIIA vs. IIIB/IIIC) (OR 2.8, p = 0.02) predicted development of IM. These findings were sustained on sensitivity analysis using different delay intervals. Median OS was not reached for the overall cohort, and was 43.1 months for patients with IM and 40.3 months in those with extracranial-only metastasis (p = 0.968). In patients with any metastasis, median OS was longer (p = 0.003) for those who experienced a treatment delay (48.4 months) compared to those that did not (12.2 months), likely due to expedited diagnosis and treatment in patients with a higher symptom burden secondary to more advanced disease. CONCLUSIONS: In patients with stage III NSCLC treated with definitive CRT, the risk of IM appears to increase with overall stage at diagnosis and, importantly, may be associated with experiencing a treatment delay (> 4 weeks). Metastatic disease of any kind remains the primary life-limiting prognostic factor in these patients with advanced lung cancer. In patients with metastatic disease, treatment delay was associated with better survival. Patients who experience a treatment delay and those initially diagnosed at a more advanced overall stage may warrant more frequent surveillance for early diagnosis and treatment of IM. Healthcare system stakeholders should strive to mitigate treatment delay in patients with locally NSCLC to reduce the risk of IM. Further research is needed to better understand factors associated with survival, treatment delay, and the development of IM after CRT in the immunotherapy era.

The impact of short term, long term and intermittent E. coli infection on male C57BL/6J mouse prostate histology and urinary physiology.

Prostatic inflammation and prostatic fibrosis are associated with lower urinary tract dysfunction in men. Prostatic inflammation arising from a transurethral uropathogenic E. coli infection is sufficient to increase prostatic collagen content in male mice. It is not known whether and how the sequence, duration and chronology of prostatic infection influence urinary function, prostatic inflammation and collagen content. We placed a transurethral catheter into adult male C57BL/6J mice to deliver uropathogenic E. coli UTI189 two-weeks prior to study endpoint (to evaluate the short-term impact of infection), 10-weeks prior to study endpoint (to evaluate the long-term impact of infection), or two-, six-, and ten-weeks prior to endpoint (to evaluate the impact of repeated intermittent infection). Mice were catheterized the same number of times across all experimental groups and instilled with sterile saline when not instilled with E. coli to control for the variable of catheterization. We measured bacterial load in free catch urine, body weight and weight of bladder and dorsal prostate; prostatic density of leukocytes, collagen and procollagen 1A1 producing cells, and urinary function. Transurethral E. coli instillation caused more severe and persistent bacteriuria in mice with a history of one or more transurethral instillations of sterile saline or E. coli. Repeated intermittent infections resulted in a greater relative bladder wet weight than single infections. However, voiding function, as measured by the void spot assay, and the density of collagen and ProCOL1A1+ cells in dorsal prostate tissue sections did not significantly differ among infection groups. The density of CD45+ leukocytes was greater in the dorsal prostate of mice infected two weeks prior to study endpoint but not in other infection groups compared to uninfected controls.

Prospective Placebo-Controlled Assessment of Spore-Based Probiotic Supplementation on Sebum Production, Skin Barrier Function, and Acne.

Probiotic supplementation has been shown to modulate the gut-skin axis. The goal of this study was to investigate whether oral spore-based probiotic ingestion modulates the gut microbiome, plasma short-chain fatty acids (SCFAs), and skin biophysical properties. This was a single-blinded, 8-week study (NCT03605108) in which 25 participants, 7 with noncystic acne, were assigned to take placebo capsules for the first 4 weeks, followed by 4 weeks of probiotic supplementation. Blood and stool collection, facial photography, sebum production, transepidermal water loss (TEWL), skin hydration measurements, and acne assessments were performed at baseline, 4, and 8 weeks. Probiotic supplementation resulted in a decreasing trend for the facial sebum excretion rate and increased TEWL overall. Subanalysis of the participants with acne showed improvement in total, noninflammatory, and inflammatory lesion counts, along with improvements in markers of gut permeability. The gut microbiome of the nonacne population had an increase in the relative abundance of Akkermansia, while the subpopulation of those with acne had an increase in the relative abundance of Lachnospiraceae and Ruminococcus gnavus. Probiotic supplementation augmented the circulating acetate/propionate ratio. There is preliminary evidence for the use of spore-based probiotic supplementation to shift the gut microbiome and augment short-chain fatty acids in those with and without acne. Further spore-based supplementation studies in those with noncystic acne are warranted.

Emerging PET Tracers in Cardiac Molecular Imaging.

18F-fluorodeoxyglucose (FDG) and 18F-sodium fluoride (NaF) represent emerging PET tracers used to assess atherosclerosis-related inflammation and molecular calcification, respectively. By localizing to sites with high glucose utilization, FDG has been used to assess myocardial viability for decades, and its role in evaluating cardiac sarcoidosis has come to represent a major application. In addition to determining late-stage changes such as loss of perfusion or viability, by targeting mechanisms present in atherosclerosis, PET-based techniques have the ability to characterize atherogenesis in the early stages to guide intervention. Although it was once thought that FDG would be a reliable indicator of ongoing plaque formation, micro-calcification as portrayed by NaF-PET/CT appears to be a superior method of monitoring disease progression. PET imaging with NaF has the additional advantage of being able to determine abnormal uptake due to coronary artery disease, which is obscured by physiologic myocardial activity on FDG-PET/CT. In this review, we discuss the evolving roles of FDG, NaF, and other PET tracers in cardiac molecular imaging.

Atherosclerosis Imaging: Positron Emission Tomography.

Assessment of molecular changes by PET has introduced a new paradigm in atherosclerosis imaging, which has traditionally relied on anatomic changes visualized by conventional angiography or computed tomography. The use of 18F-fluorodeoxyglucose (FDG) to identify atherosclerotic changes in the vessel wall was first described more than 2 decades ago. Since then, PET tracers targeting macrophage activity, neoangiogenesis, smooth muscle activity, and other aspects of atherogenic changes have been proposed. The evolving roles of PET tracers including frontrunners FDG and 18F-sodium fluoride, which show arterial wall inflammation and microcalcification, respectively, are discussed.

Revisiting implementation of multiple natural enemies in pest management.

A major goal of biological control is the reduction and/or eradication of pests using various natural enemies, in particular, via deliberate infection of the target species by parasites. To enhance the biological control, a promising strategy seems to implement a multi-enemy assemblage rather than a single control agent. Although a large body of theoretical studies exists on co-infections in epidemiology and ecology, there is still a big gap in modelling outcomes of multi-enemy biological control. Here we theoretically investigate how the efficiency of biological control of a pest depends on the number of natural enemies used. We implement a combination of eco-epidemiological modelling and the Adaptive Dynamics game theory framework. We found that a progressive addition of parasite species increases the evolutionarily stable virulence of each parasite, and thus enhances the mortality of the target pest. However, using multiple enemies may have only a marginal effect on the success of biological control, or can even be counter-productive when the number of enemies is excessive. We found the possibility of evolutionary suicide, where one or several parasite species go extinct over the course of evolution. Finally, we demonstrate an interesting scenario of coexistence of multiple parasites at the edge of extinction.

Investigating Cutaneous Squamous Cell Carcinoma in vitro and in vivo: Novel 3D Tools and Animal Models.

Cutaneous Squamous Cell Carcinoma (cSCC) represents the second most common type of skin cancer, which incidence is continuously increasing worldwide. Given its high frequency, cSCC represents a major public health problem. Therefore, to provide the best patients' care, it is necessary having a detailed understanding of the molecular processes underlying cSCC development, progression, and invasion. Extensive efforts have been made in developing new models allowing to study the molecular pathogenesis of solid tumors, including cSCC tumors. Traditionally, in vitro studies were performed with cells grown in a two-dimensional context, which, however, does not represent the complexity of tumor in vivo. In the recent years, new in vitro models have been developed aiming to mimic the three-dimensionality (3D) of the tumor, allowing the evaluation of tumor cell-cell and tumor-microenvironment interaction in an in vivo-like setting. These models include spheroids, organotypic cultures, skin reconstructs and organoids. Although 3D models demonstrate high potential to enhance the overall knowledge in cancer research, they lack systemic components which may be solved only by using animal models. Zebrafish is emerging as an alternative xenotransplant model in cancer research, offering a high-throughput approach for drug screening and real-time in vivo imaging to study cell invasion. Moreover, several categories of mouse models were developed for pre-clinical purpose, including xeno- and syngeneic transplantation models, autochthonous models of chemically or UV-induced skin squamous carcinogenesis, and genetically engineered mouse models (GEMMs) of cSCC. These models have been instrumental in examining the molecular mechanisms of cSCC and drug response in an in vivo setting. The present review proposes an overview of in vitro, particularly 3D, and in vivo models and their application in cutaneous SCC research.

Lifetime caffeine intake and the risk of epithelial ovarian cancer.

BACKGROUND: Caffeine intake has been inconsistently associated with the risk of ovarian cancer in previous studies. The measure of caffeine in these studies has not always distinguished between caffeinated and decaffeinated sources, and the time for which intake was assessed was often for late adulthood and thus may have excluded the etiologic window. We investigated lifetime caffeine intake from caffeinated coffee, black tea, green tea and cola sodas in relation to ovarian cancer risk. METHODS: Among 497 cases and 904 controls in a population-based case-control study in Montreal, Canada, lifetime intake of caffeinated coffee, black tea, green tea and cola sodas was assessed and used to calculate lifetime total intake of caffeine. Unconditional multivariable logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the association between caffeine intake and ovarian cancer risk overall, as well as by menopausal status. Multivariable polytomous logistic regression was used to estimate the associations for invasive and borderline ovarian cancers separately. RESULTS: Almost all participants (98.4% of cases and 97.5% of controls) had consumed caffeine in their lifetime. The mean (standard deviation) daily consumption of caffeine over the lifetime was of 117 (89) mg/day among cases and 120 (118) mg/day among controls. The OR (95% CI) of ovarian cancer for the highest versus lowest quartile of lifetime caffeine intake was 1.17 (0.83-1.64). According to menopausal status, the OR (95% CI) was 1.56 (0.85-2.86) for premenopausal women and 0.94 (0.66-1.34) for postmenopausal women, comparing the highest to lowest tertiles of intake. Associations for invasive and borderline ovarian cancers separately were similar to that observed for ovarian cancer overall. CONCLUSION: Lifetime caffeine intake was not strongly associated with ovarian cancer risk. A difference in relationship by menopausal status is possible.

How does feedback from phage infections influence the evolution of phase variation in Campylobacter?

Campylobacter jejuni (C. jejuni) causes gastroenteritis following the consumption of contaminated poultry meat, resulting in a large health and economic burden worldwide. Phage therapy is a promising technique for eradicating C. jejuni from poultry flocks and chicken carcasses. However, C. jejuni can resist infections by some phages through stochastic, phase-variable ON/OFF switching of the phage receptors mediated by simple sequence repeats (SSR). While selection strength and exposure time influence the evolution of SSR-mediated phase variation (PV), phages offer a more complex evolutionary environment as phage replication depends on having a permissive host organism. Here, we build and explore several continuous culture bacteria-phage computational models, each analysing different phase-variable scenarios calibrated to the experimental SSR rates of C. jejuni loci and replication parameters for the F336 phage. We simulate the evolution of PV rates via the adaptive dynamics framework for varying levels of selective pressures that act on the phage-resistant state. Our results indicate that growth reducing counter-selection on a single PV locus results in the stable maintenance of the phage, while compensatory selection between bacterial states affects the evolutionary stable mutation rates (i.e. very high and very low mutation rates are evolutionarily disadvantageous), whereas, in the absence of either selective pressure the evolution of PV rates results in mutation rates below the basal values. Contrastingly, a biologically-relevant model with two phase-variable loci resulted in phage extinction and locking of the bacteria into a phage-resistant state suggesting that another counter-selective pressure is required, instance, the use of a distinct phage whose receptor is an F336-phage-resistant state. We conclude that a delicate balance between counter-selection and phage-attack can result in both the evolution of phase-variable phage receptors and persistence of PV-receptor-specific phage.

Revisiting the Role of Hyperparasitism in the Evolution of Virulence.

AbstractHyperparasitism denotes the natural phenomenon where a parasite infecting a host is in turn infected by its own parasite. Hyperparasites can shape the dynamics of host-parasite interactions and often have a deleterious impact on pathogens, an important class of parasites, causing a reduction in their virulence and transmission rate. Hyperparasitism thus could be an important tool of biological control. However, host-parasite-hyperparasite systems have so far been outside the mainstream of modeling studies, especially those dealing with eco-evolutionary aspects of species interactions. Here, we theoretically explore the evolution of life-history traits in a generic host-parasite-hyperparasite system, focusing on parasite virulence and the positive impact that hyperparasitism has on the host population. We also explore the coevolution of life-history traits of the parasite and hyperparasite, using adaptive dynamics and quantitative genetics frameworks to identify evolutionarily singular strategies. We find that in the presence of hyperparasites, the evolutionarily optimal pathogen virulence generally shifts toward more virulent strains. However, even in this case the use of hyperparasites in biocontrol could be justified, since overall host mortality decreases. An intriguing possible outcome of the evolution of the hyperparasite can be its evolutionary suicide.

A uropathogenic E. coli UTI89 model of prostatic inflammation and collagen accumulation for use in studying aberrant collagen production in the prostate.

Bacterial infection is one known etiology of prostatic inflammation. Prostatic inflammation is associated with prostatic collagen accumulation and both are linked to progressive lower urinary tract symptoms in men. We characterized a model of prostatic inflammation using transurethral instillations of Escherichia coli UTI89 in C57BL/6J male mice with the goal of determining the optimal instillation conditions, understanding the impact of instillation conditions on urinary physiology, and identifying ideal prostatic lobes and collagen 1a1 prostatic cell types for further analysis. The smallest instillation volume tested (50 µL) distributed exclusively to the bladder, 100- and 200-µL volumes distributed to the bladder and prostate, and a 500-µL volume distributed to the bladder, prostate, and ureter. A threshold optical density of 0.4 E. coli UTI89 in the instillation fluid was necessary for significant (P < 0.05) prostate colonization. E. coli UTI89 infection resulted in a low frequency, high volume spontaneous voiding pattern. This phenotype was due to exposure to E. coli UTI89, not catheterization alone, and was minimally altered by a 50-µL increase in instillation volume and doubling of E. coli concentration. Prostate inflammation was isolated to the dorsal prostate and was accompanied by increased collagen density. This was partnered with increased density of protein tyrosine phosphatase receptor type C+, procollagen type I-α1+ copositive cells and decreased density of α2-smooth muscle actin+, procollagen type I-α1+ copositive cells. Overall, we determined that this model is effective in altering urinary phenotype and producing prostatic inflammation and collagen accumulation in mice.

Randomized double-blind vehicle controlled study of the effects of topical acetyl zingerone on photoaging.

OBJECTIVE: Acetyl zingerone (AZ), a derivative of the phytochemical zingerone from Zingiber officinale (ginger), is a novel compound that is purported to have antiaging properties. The objective of this clinical study was to assess the role of acetyl zingerone in its ability to improve the appearance of facial skin wrinkles, redness, pigmentation, and photoaging was assessed. METHODS: Thirty-one healthy participants (age 44 ± 7 years) were randomized in blinded fashion to apply either 1% AZ or placebo, consisting of the vehicle base cream, to the full face twice daily for 8 weeks with a total of 3 visits. Signs of photoaging, including wrinkles, dyspigmentation, and redness were assessed with facial image analysis photography and software. RESULTS: There was a significant decrease in average wrinkle severity (P = .019; Mean=-25.7% change), total wrinkle volume (P = .003; Mean=-30.1% change), pigment intensity (P = .021; Mean=-25.6% change), and redness intensity (P = .035; Mean=-20.7% change) in the AZ group by 8 weeks compared with the placebo. No significant itching, burning, or stinging was noted by study participants. There was also no significant difference between both groups in the clinical assessment of scaling, erythema, hypopigmentation, or hyperpigmentation. CONCLUSIONS AND RELEVANCE: Topical AZ improves photodamage and decreases the appearance of wrinkles, dyspigmentation, and redness intensity when compared to placebo (vehicle) formulation. Acetyl zingerone is well tolerated with daily use.

A retrospective review of canine benign prostatic hyperplasia with and without prostatitis.

Benign prostatic hyperplasia (BPH) is the most common prostatic disorder in older intact male dogs, but despite its prevalence, there are inconsistencies in clinical diagnosis and treatment. Although prostate size was historically considered the hallmark feature of BPH in men, currently, there is only a weak correlation between prostate size and clinical severity. We performed a retrospective cohort study with the primary objective of assessing clinical signs, ultrasonographic findings, treatments, and outcomes in dogs diagnosed with BPH, with and without concurrent prostatitis. We reviewed medical records and obtained data on presenting signs, prostatic imaging, and prevalence of concurrent bacteriuria. Prostate size was determined by ultrasonography and compared to the calculated expected size based on patient age and weight. Treatment and outcome were described for the cases with a minimum 2 months follow-up. Median age of dogs diagnosed with BPH was 8 years. Clinical signs were present in 16/25 dogs and scored as mild to moderate (median Zambelli's Symptom Index for BPH score 12). The median prostatic volume to body mass ratio was 1.60 mm3/kg. Prostate size did not correlate with the symptom severity. Concurrent bacteriuria was confirmed in 4/25 cases via bacterial culture and/or cytology. Treatments pursued and responses were only available in a subpopulation of dogs (n = 9) and were highly variable. Studies are needed to determine if current treatment options for BPH in dogs resolve associated clinical signs in addition to reducing prostate size.

Urethral luminal epithelia are castration-insensitive cells of the proximal prostate.

BACKGROUND: Castration-insensitive epithelial progenitors capable of regenerating the prostate have been proposed to be concentrated in the proximal region based on facultative assays. Functional characterization of prostate epithelial populations isolated with individual cell surface markers has failed to provide a consensus on the anatomical and transcriptional identity of proximal prostate progenitors. METHODS: Here, we use single-cell RNA sequencing to obtain a complete transcriptomic profile of all epithelial cells in the mouse prostate and urethra to objectively identify cellular subtypes. Pan-transcriptomic comparison to human prostate cell types identified a mouse equivalent of human urethral luminal cells, which highly expressed putative prostate progenitor markers. Validation of the urethral luminal cell cluster was performed using immunostaining and flow cytometry. RESULTS: Our data reveal that previously identified facultative progenitors marked by Trop2, Sca-1, KRT4, and PSCA are actually luminal epithelial cells of the urethra that extend into the proximal region of the prostate, and are resistant to castration-induced androgen deprivation. Mouse urethral luminal cells were identified to be the equivalent of previously identified human club and hillock cells that similarly extend into proximal prostate ducts. Benign prostatic hyperplasia (BPH) has long been considered an "embryonic reawakening," but the cellular origin of the hyperplastic growth concentrated in the periurethral region is unclear. We demonstrate an increase in urethral luminal cells within glandular nodules from BPH patients. Urethral luminal cells are further increased in patients treated with a 5-α reductase inhibitor. CONCLUSIONS: Our data demonstrate that cells of the proximal prostate that express putative progenitor markers, and are enriched by castration in the proximal prostate, are urethral luminal cells and that these cells may play an important role in the etiology of human BPH.