Identification and drug resistance of pathogen of ulcerative skin disease and its immune responses and protective efficacy after vaccination in a giant spiny frog, Quasipaa spinosa.

OBJECTIVE: In order to explore the pathogen of the ulcerative skin disease in giant spiny frog (Quasipaa spinosa), and to provide theoretical basis for the prevention and control of the disease in practical production, this study was carried out to isolate and identify the pathogenic bacteria from the sick frogs suffering from rotting skin disease and to carry out the immunization test of the inactivated vaccine. METHODS: Physiological and biochemical characterization, and molecular biology of the pathogenic bacteria were identified, and drug screening and immunization responses were also carried out. RESULTS: The dominant bacterium QS01 was isolated from the lesions of diseased giant spiny frogs, which was confirmed to be the causative agent of the rotting skin disease of giant spiny frogs by artificial regression infection test. Based on the fact that the pathogen is a gram-negative short bacterium, its phenotypic characteristics and 16S rRNA and gyrB gene sequences were analyzed, and the bacterium was determined to be Citrobacter freundii. The results of the drug sensitivity test showed that the bacterium was sensitive to 11 antibiotics, including Enrofloxacin, Fleroxacin and Ciprofloxacin, including three non-polluting drugs such as Florfenicol, Roxithromycin and Thiamphenicol, as well as three Chinese herbal medicines such as Rheum officinale Baill, Coptis chinensis Franch and Scutellaria baicalensis Georgi. Most non-specific immune responses could go to recovery in 24h. The frogs were vaccinated with QS01 formaldehyde inactivated vaccine by injection, immersion and spraying, and the serum antibody potency of the three immunized groups with the average potency reached the peak at the 20th d after immunization, and the serum antibody potency of the injected immunized group was at the highest ratio of 1:64-128 (101.6), while the immersed group and the spraying group attained the ratio of 1:16-32 (20.2) and 1:16-32 (16) respectively, and lasted until the 30th d. The control group that was not immunized had the highest serum antibody potency of 1:16-32 (20.2) and 1:16-32 (16), and continued until the 30th d. The control group that was not immunized was not immunized. The serum antibody potency of the unimmunized control group was 1:2 to 2(2). The immunoprotection rates after takedown were 100 %, 85.71 % and 71.43 %, respectively. CONCLUSION: C. freundii is the pathogen of the disease in this farm, and the vaccination by immersion and spraying can effectively prevent and control the rotting skin disease in frogs. These results revealed pathogenicity of C. freundii and its activation of host immune response, which will provide a scientific reference for the aquaculture and disease prevention in Q. spinosa culture.

Marijuana use disorder among adults with functional disabilities-A US population-based cross-sectional study.

BACKGROUND AND OBJECTIVES: Recent studies suggest a growing trend in marijuana use, compared to a stable prevalence of marijuana use disorder among US adults over the first 15 years of the 21st century. This study investigated the recent patterns of marijuana use disorder among people with disabilities (PWD). METHODS: We extracted a nationally representative sample (N = 209,058) from the 2015-2019 National Survey on Drug Use and Health data set and examined associations by functional disability status (any disability, disability by type, and number of disabling limitations) with marijuana use disorder using a series of independent multivariable logistic regression models. We also performed trend analyses during the study period. RESULTS: The prevalence of marijuana use disorder (from 1.7% to 2.3%) increased significantly among PWD between 2015 and 2019 (p-trend < .001). PWD were significantly more likely to report marijuana use disorder (odds ratio [OR], 1.37, 95% confidence interval [CI], 1.24-1.52) than people without disability (PWoD). Those with cognitive limitation only (OR, 1.78, 95% CI, 1.53-2.06) and ≥2 limitations (OR, 1.29, 95% CI, 1.10-1.51) were more likely to report marijuana use disorder than PWoD. DISCUSSION AND CONCLUSIONS: PWD had a consistently higher prevalence of marijuana use disorder than PWoD. Additionally, the level of risk for marijuana use disorder varied by disability type and number of disabling limitations. SCIENTIFIC SIGNIFICANCE: Our study provided new nuance on disparities in marijuana use disorder between PWD and PWoD and further revealed the varied risks for marijuana use disorder across different disability statuses.

Carbon Dots and Tumor Antigen Conjugates as Nanovaccines for Elevated Cancer Immunotherapy.

Cancer immunotherapy has become one of the current research hotspots. However, the deficiencies including restricted immunogenicity, insufficient antigen presentation, and low responsive rate limited their therapeutic applications. Own to the small size and excellent biocompatibility, carbon dots (CDs) can serve as nanovectors to improve the efficacy of cancer immunotherapy. Herein, a tumor antigen-based nanovaccines (GMal+B16F10-Ag and GMal+CT26-Ag) by the conjugation of CDs with the tumor cell-derived antigens (B16F10-Ag and CT26-Ag) is constructed. These nanovaccines can be effectively taken up by dendritic cells (DC2.4), promote DC cell maturation, cross-present the antigen to T cells, specifically target B16F10 melanoma or CT26 colon cancers, and inhibit tumor growth distinctly. This work illustrates the promise of CDs acting as versatile carriers for antigen delivery to achieve the optimal immunotherapeutic outcomes.

People With Functional Disability and Access to Health Care During the COVID-19 Pandemic: A US Population-based Study.

INTRODUCTION: The COVID-19 pandemic and nationwide restriction measures have disrupted health care delivery and access for the general population. There is limited evidence about access to care issues (delayed and forgone care) due to the pandemic among people with disability (PWD). METHODS: This study used the 2020 National Health Interview Survey data. Disability status was defined by disability severity (moderate and severe disability), type, and the number of disabling limitations. Descriptive analysis and multivariate logistic regression (adjusted for sociodemographic and health-related characteristics) were conducted to estimate delayed/forgone care (yes/no) between PWD and people without disability (PWoD). RESULTS: Among 17,528 US adults, 40.7% reported living with disability. A higher proportion of respondents with severe and moderate disability reported delaying care than PWoD (severe=33.2%; moderate=27.5%; PWoD=20.0%, P <0.001). The same was true for forgone medical care (severe=26.6%; moderate=19.0%; PWoD=12.2%, P <0.001). Respondents with a moderate disability {delayed [odds ratio (OR)=1.33, 95% confidence interval (CI)=1.19, 1.49]; forgone [OR=1.46, 95% CI=1.28, 1.67]} and a severe disability [delayed (OR=1.52, 95% CI=1.27, 1.83); forgone (OR=1.84, 95% CI=1.49, 2.27)] were more likely to report delayed medical care and forgone medical care compared with PWoD. These findings were consistent across the models using disability type and the number of limitations. CONCLUSIONS: PWD were more likely to experience COVID-19-related delays in or forgone medical care compared with PWoD. The more severe and higher frequency of disabling limitations were associated with higher degrees of delayed and forgone medical care. Policymakers need to develop disability-inclusive responses to public health emergencies and postpandemic care provision among PWD.

Association of Medicaid expansion with 2-year survival and time to treatment initiation in gastrointestinal cancer patients: A National Cancer Database study.

INTRODUCTION: We evaluated whether Medicaid expansion (ME) was associated with improved 2-year survival and time to treatment initiation (TTI) among patients with gastrointestinal (GI) cancer. METHODS: GI cancer patients diagnosed 40-64 years were queried from the National Cancer Database. Those diagnosed from 2010 to 2012 were considered pre-expansion; those diagnosed from 2014 to 2016 were considered post-expansion. Cox models estimated hazard ratios and 95% confidence intervals (CIs) for 2-year overall survival. Generalized estimating equations (GEE) estimated odds ratios (OR) and 95% CI of TTI within 30- and 90 days. Multivariable Difference-in-Difference models were used to compare expansion/nonexpansion cohorts pre-/post-expansion, adjusting for patient, clinical, and hospital factors. RESULTS: 377,063 patients were included. No significant difference in 2-year survival was demonstrated across ME and non-ME states overall or in site-based subgroup analysis. In stage-based subgroup analysis, 2-year survival significantly improved among stage II cancer, with an 8% decreased hazard of death at 2 years (0.92; 0.87-0.97). Those with stage IV had a 4% increased hazard of death at 2 years (1.04; 1.01-1.07). Multivariable GEE models showed increased TTI within 30 days (1.12; 1.09-1.16) and 90 days (1.22; 1.17-1.27). Site-based subgroup analyses indicated increased likelihood of TTI within 30 and 90 days among colon, liver, pancreas, rectum, and stomach cancers, by 30 days for small intestinal cancer, and by 90 days for esophageal cancer. In subgroup analyses, all stages experienced improved odds of TTI within 30 and 90 days. CONCLUSION: ME was not associated with significant improvement in 2-year survival for those with GI cancer. Although TTI increased after ME for both cohorts, the 30- and 90-day odds of TTI was higher for those from ME compared with non-ME states. Our findings add to growing evidence of associations with ME for those diagnosed with GI cancer.

A near-infrared probe for detecting and interposing amyloid beta oligomerization in early Alzheimer's disease.

BACKGROUND: The misfolding and deposition of amyloid beta (Aß) in human brain is the main hallmark of Alzheimer's disease (AD) pathology. One of the drivers of Alzheimer´s pathogenesis is the production of soluble oligomeric Aß, which could potentially serve as a biomarker of AD. METHODS: Given that the diphenylalanine (FF) at the C-terminus of Aß fragments plays a key role in inducing the AD pathology, based on the hydrophobic structure of FF, we synthesized a near-infrared BF2-dipyrrolmethane fluorescent imaging probe (NB) to detect both soluble and insoluble Aß. RESULTS: We found that NB not only binds Aß, particularly oligomeric Aß, but also interposes self-assembly of Aß through π-π interaction between NB and FF. CONCLUSION: This work holds great promise in the early detection of AD and may also provide an innovative approach to decelerate and even halt AD onset and progression.

Utilization of inpatient palliative care services among adolescents and young adults with cancer: Evidence from National Inpatient Sample 2016-2019.

OBJECTIVES: Palliative care can improve the quality of life of adolescents and young adults (AYA) with cancer. However, little is known about the utilization of palliative care among AYA cancer patients. Identifying factors associated with the utilization of palliative care could inform efforts to improve palliative care access among AYA patients living with cancer. METHODS: Using data from the National Inpatient Sample 2016-2019, a representative sample of US hospitalizations, we examined palliative care encounters and associated characteristics among hospitalizations of AYA with cancer and high inpatient mortality risk. Survey design-adjusted bivariate and multivariable logistic regression models were used to examine associations of patient- and hospital-level characteristics with palliative care. RESULTS: Of 10,979 hospitalizations by AYA cancer patients with high mortality risk, 19.9% received palliative care services between 2016 and 2019. After adjusting for all characteristics, independent predictors of palliative care use were as follows: older age (25-39 years old vs. 25-39 years; odds ratio [OR] 1.31, 95% confidence interval [CI] 1.15-1.49), Hispanic/Latinx (vs. non-Hispanic White; OR 1.16, 95% CI 1.01-1.34), female (vs. male; OR 1.27, 95% CI 1.14-1.41), public insurance (vs. private insurance; OR 1.23, 95% CI 1.10-1.38), hospital location in the US South (vs. Northeast; OR 0.78, 95% CI 0.66-0.94), and a large hospital (vs. small; OR 0.83, 95% CI 0.72-0.96). SIGNIFICANCE OF RESULTS: Less than 20% of AYAs with cancer and high risk of mortality received inpatient palliative care services. Further research is needed to explore the reasons for lower palliative care utilization in the younger age groups.

Endocrine adherence in male versus female breast cancer: a seer-medicare review.

PURPOSE: Breast cancer in men (BC-M) is almost exclusively hormone receptor positive. We conducted a large review of the SEER-Medicare linked database to compare endocrine therapy adherence, discontinuation, and survival outcomes of male versus female patients with breast cancer. METHODS: Study data were obtained through the SEER-Medicare linked database. The study included patients age ≥ 65 years-old diagnosed with breast cancer between 2007 and 2015. The primary endpoints were rates of adherence and discontinuation of endocrine therapy (ET). Adherence was defined as a gap of less than 90 days in-between consecutive Medicare prescriptions. Discontinuation was defined as a gap of greater than 12 months in-between Medicare prescriptions. Secondary endpoint was the association of use of ET with overall survival (OS). RESULTS: Of the 363 male patients on ET, 214 patients (59.0%) were adherent to the therapy, and 149 patients (41.0%) were nonadherent. Of the 20,722 females on ET, 10,752 (51.9%) were adherent to the therapy, and 9970 (48.1%) were nonadherent. 39 male patients (10.7%) discontinued therapy, while 324 (89.3%) did not discontinue therapy. 1849 female patients (8.9%) discontinued therapy, while 18,873 (91.1%) patients did not. Men were significantly more adherent than women (p = 0.008), but there was no significant difference in discontinuation among men and women (p = 0.228). Survival was significantly improved in both men (HR 0.77, 95% CI 0.60-0.99, p = 0.039) and women (HR 0.84, 95% CI 0.81-0.87, p < 0.001) on ET. CONCLUSION: Identification of contributing factors impacting adherence and discontinuation is needed to allow physicians to address barriers to long term use of ET.

Deep Tumor Penetrating Gold Nano-Adjuvant for NIR-II-Triggered In Situ Tumor Vaccination.

Local tumor photothermal treatment with the near-infrared light at the second window (NIR-II) is a promising strategy in triggering the in situ tumor vaccination (ISTV) for cancer therapy. However, limited penetration of photothermal agents within tumors seriously limits their spatial effect in generating sufficient tumor-associated antigens, a key factor to the success of ISTV. In this study, a nano-adjuvant system is fabricated based on the NIR-II-absorbable gold nanostars decorated with hyaluronidases and immunostimulatory oligodeoxynucleotides CpG for ISTV. The nano-adjuvant displays a deep tumor penetration capacity via loosening the dense extracellular matrix of tumors. Upon NIR-II light irradiation, the nano-adjuvant significantly inhibits the tumor growth, induces a cascade of immune responses, generates an obvious adaptive immunity against the re-challenged cancers, boosts the abscopal effect, and completely inhibits the pulmonary metastases. The study highlights an advanced nano-adjuvant formulation featuring deep tumor penetration for NIR-II-triggered ISTV.

A general carbon dot-based platform for intracellular delivery of proteins.

The shortcomings of proteins, such as poor stability in biological environments, the impermeability of the membrane and the susceptibility to enzymolysis, restrict their potential applications. Therefore, constructing universal nanocarriers for intracellular delivery of a variety of proteins remains a great challenge. In this work, gallic acid (GA) and L-lysine were used as starting materials to synthesize carbon dots (CDs). The CDs were used as carriers to interact with bovine serum albumin (BSA), enhanced green fluorescent protein (EGFP) and glucose oxidase (GOx) via supramolecular interaction to construct CDs-protein nanocomposites CDs-BSA, CDs-EGFP and CDs-GOx. Furthermore, CDs-EGFP and CDs-GOx can achieve intracellular protein delivery and maintain 89% of the biological activity of GOx. In this work, the latency of CDs is projected as a universal platform for effective intracellular delivery of proteins.

Multivariate Strategy Preparation of Nanoscale Ru-Doped Metal-Organic Frameworks with Boosted Photoactivity for Bioimaging and Reactive Oxygen Species Generation.

How to incorporate chromophores into MOFs is a key for the development of multifunctional photoactive systems. The poor internalization by cancer cells and low efficiency of ROS generation hamper the potential clinic application of Ru-based molecular agents. In this work, a nanoscale Ru-doped metal-organic framework Hf-UiO-Ru (Hf-Ru) with framework-boosted photoactivities was prepared via a multivariate strategy for use in bioimaging and ROS generation. The as-synthesized Hf-Ru nanocrystals not only maintain the well regular morphology and crystal structure in comparison with that of the Hf-UiO-66 prototype but also give an oxygen-independent emission with a much longer lifetime, higher quantum yield, and stronger ROS generation than molecular Ru(dcbpy)3. Additionally, the enhanced cellular uptake and high brightness in fluorescence and CT imaging of Hf-Ru nanocrystals have also been well studied in vitro. This multivariate strategy may be utilized as a general paradigm to develop a photoactive nanosystem for bioimaging and cancer treatment.

Injectable self-healing hydrogel fabricated from antibacterial carbon dots and ɛ-polylysine for promoting bacteria-infected wound healing.

Developing highly efficient pharmaceuticals to eradicate pathogens and facilitate wound healing is of great concern. Despite some cationic carbon dots (CDs) have been used for sterilization, hardly any anionic CDs with antimicrobial activity have appeared. In the present work, we engineered a string of anionic CDs (especially CD31) as valid broad-spectrum bactericides to kill bacteria. Furthermore, CD31 conjugated with ɛ-polylysine (Plys) to construct injectable, and self-healing hydrogel (CD-Plys) that possess the advantages of remarkable broad spectrum antibacterial activity, excellent wound healing ability and satisfied biocompatibility. CD-Plys could dramatically accelerate wound healing with epithelization and enhanced angiogenesis. Taken together, this work provides a two-pronged strategy to explore CDs-based antimicrobial agents for disease therapy and tissue engineering.

Two-dimensional metal-organic frameworks: from synthesis to bioapplications.

As a typical class of crystalline porous materials, metal-organic framework possesses unique features including versatile functionality, structural and compositional tunability. After being reduced to two-dimension, ultrathin metal-organic framework layers possess more external excellent properties favoring various technological applications. In this review article, the unique structural properties of the ultrathin metal-organic framework nanosheets benefiting from the planar topography were highlighted, involving light transmittance, and electrical conductivity. Moreover, the design strategy and versatile fabrication methodology were summarized covering discussions on their applicability and accessibility, especially for porphyritic metal-organic framework nanosheet. The current achievements in the bioapplications of two-dimensional metal-organic frameworks were presented comprising biocatalysis, biosensor, and theranostic, with an emphasis on reactive oxygen species-based nanomedicine for oncology treatment. Furthermore, current challenges confronting the utilization of two-dimensional metal-organic frameworks and future opportunities in emerging research frontiers were presented.

Ionic Covalent-Organic Framework Nanozyme as Effective Cascade Catalyst against Bacterial Wound Infection.

The increasing resistance risks of conventional antibiotic abuse and the formed biofilm on the surface of wounds have been demonstrated to be the main problems for bacteria-caused infections and unsuccessful wound healing. Treatment by reactive oxygen species, such as the commercial H2 O2 , is a feasible way to solve those problems, but limits in its lower efficiency. Herein, an ionic covalent-organic framework-based nanozyme (GFeF) with self-promoting antibacterial effect and good biocompatibility has been developed as glucose-triggered cascade catalyst against bacterial wound infection. Besides the efficient conversion of glucose to hydrogen peroxide, the produced gluconic acid by loading glucose oxidase can supply a compatible catalytic environment to substantially improve the peroxidase activity for generating more toxic hydroxyl radicals. Meanwhile, the adhesion between the positively charged GFeF and the bacterial membrane can greatly enhance the healing effects. This glucose-triggered cascade strategy can reduce the harmful side effects by indirectly producing H2 O2 , potentially used in the wound healing of diabetic patients.

Reduction-Sensitive Fluorinated-Pt(IV) Universal Transfection Nanoplatform Facilitating CT45-Targeted CRISPR/dCas9 Activation for Synergistic and Individualized Treatment of Ovarian Cancer.

Compared to traditional clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) system, CRISPR/dead Cas9 (dCas9) system can precisely regulate endogenous gene expression without damaging the host gene, representing a greater potential for cancer therapy. Cancer/testis antigen 45 (CT45) is proved to enhance platinum-based chemosensitivity for individualized ovarian cancer therapy. However, the development of a single nanocarrier codelivering CRISPR/dCas9 system and chemotherapeutics for synergistic cancer therapy still faces challenges. Herein, a reduction-sensitive fluorinated-Pt(IV) universal transfection nanoplatform (PtUTP-F) is developed for the CT45-targeted CRISPR/dCas9 activation to achieve synergistic and individualized treatment of ovarian cancer. Overcoming multiple physiological barriers, PtUTP-F condensed gene can efficiently transfect into different cells including 293T cells, A2780, SKOV3, A549, and A2780/cisplatin (DDP) cancer cells, which is superior to Lipofectamine 6000. With the responsive release of gene and Pt(II) in the intracellular reducing microenvironment, PtUTP-F/dCas9-CT45 can generate CRISPR/dCas9 activation of CT45 expression for protein phosphatase 4C (PP4C) activity inhibition to hinder the DNA repair pathway and thus enhances the sensitivity to Pt(II) drugs for individualized A2780 tumor therapy. The PtUTP-F not only represents a powerful nanoplatform for CRISPR/dCas9 system delivery but also initiates a novel strategy for synergistic and individualized treatment of CRISPR/dCas9-based gene therapy with chemotherapy.

Self-assembly of chiral foldamers with alternating hydrophilic and hydrophobic side chains into acid-sensitive and solvent-exchangeable vesicular particles.

It is difficult for the same molecule to self-assemble into stable vesicular particles in water and aliphatic hydrocarbon (oil), respectively. Here we demonstrated that chiral oligo(methylene-p-phenyleneethynylene)s with alternating hydrophilic and hydrophobic side chains were able to self-assemble into vesicular particles independent of solvent polarity. These particles were well dispersed in aliphatic hydrocarbon, alcohol or water for at least one month at room temperature, and readily transferred from organic to aqueous phases via dialysis. They displayed a noticeable response to the acidity of the aqueous phase, and could be used as simple cargos for loading hydrophilic or hydrophobic molecules in aqueous cores, which were different from loading in polymersomes. The vesicular particles loaded with hydrophobic paclitaxel exhibited comparable anti-HeLa cell activity to free paclitaxel in vitro.

Defect Engineering of Nanoscale Hf-Based Metal-Organic Frameworks for Highly Efficient Iodine Capture.

With the rapid development of the nuclear industry, how to deal with radioactive iodine waste in a timely and effective manner has become an important issue to be solved urgently. Herein, the defect-engineering strategy has been applied to develop a metal-organic framework (MOF)-based solid adsorbent by using the classical UiO-type Hf-UiO-66 as an example. After simple acid treatment, the produced defect-containing Hf-UiO-66 (DHUN) not only retains its topological structure, high crystallization, and regular shape but also shows a great increase in the Brunauer-Emmett-Teller value and pore size in comparison with the original Hf-UiO (HUN). These formed defects within DHUN have been demonstrated to be important for the great enhancement of the iodine capture and following application in computed tomography imaging in vitro. This present work gives a new insight into the control and formation of defect sites, and this simple and efficient defect-engineering strategy also shows great promise for the development of novel solid adsorbents and other functional MOF materials.

A redox-responsive dihydroartemisinin dimeric nanoprodrug for enhanced antitumor activity.

Redox-responsive drug delivery system emerges as a hopeful platform for tumor treatment. Dihydroartemisinin (DHA) has been investigated as an innovative tumor therapeutic agent. Herein, a DHA dimeric prodrug bridged with disulfide bond as linker (DHA2-SS) has been designed and synthesized. The prepared prodrugs could self-assemble into nanoparticles (SS NPs) with high DHA content (> 90%) and robust stability. These SS NPs display sensitive redox responsive capability and can release DHA under the tumor heterogeneity microenvironment. SS NPs possess preferable antitumor therapeutic activity in contrast with free DHA. Moreover, the possible anti-cancer mechanism of SS NPs was investigated through RNA-seq analysis, bioinformatics and molecular biological method. SS NPs could induce apoptosis via mitochondrial apoptosis pathway, as well as glycolysis inhibition associate with the regulation of PI3K/AKT/HIF-1α signal path, which may offer an underlying therapeutic target for liver cancer. Our study highlights the potential of using redox responsive prodrug nanoparticles to treat cancer, meanwhile provides insights into the anti-cancer mechanism of DHA prodrug.

The neural stem cell/carnitine malnutrition hypothesis: new prospects for effective reduction of autism risk?

Autism spectrum disorders (ASDs) are developmental neuropsychiatric disorders with heterogeneous etiologies. As the incidence of these disorders is rising, such disorders represent a major human health problem with escalating social cost. Although recent years witnessed advances in our understanding of the genetic basis of some dysmorphic ASDs, little progress has been made in translating the improved understanding into effective strategies for ASD management or minimization of general ASD risk. Here we explore the idea, described in terms of the neural stem cell (NSC)/carnitine malnutrition hypothesis, that an unappreciated risk factor for ASD is diminished capacity for carnitine-dependent long-chain fatty acid ß-oxidation in neural stem cells of the developing mammalian brain. The basic premise is that fetal carnitine status is a significant metabolic component in determining NSC vulnerability to derangements in their self-renewal program and, therefore, to fetal ASD risk. As fetal carnitine status exhibits a genetic component that relates to de novo carnitine biosynthesis and is sensitive to environmental and behavioral factors that affect maternal circulating carnitine levels, to which the fetus is exposed, we propose that reduced carnitine availability during gestation is a common risk factor that lurks beneath the genetically complex ASD horizon. One major prediction of the NSC/carnitine malnutrition hypothesis is that a significant component of ASD risk might be effectively managed from a public policy perspective by implementing a carnitine surveillance and dietary supplementation strategy for women planning pregnancies and for women in their first trimester of pregnancy. We argue that this prediction deserves serious clinical interrogation.

Outcomes of primary endocrine therapy in elderly women with stage I-III breast cancer: a SEER database analysis.

BACKGROUND: Frail elderly women with nonmetastatic hormone receptor-positive breast cancer often receive primary endocrine therapy. Limited data are available on the outcomes associated with this population and treatment approach. METHODS: We selected patients with an initial primary diagnosis of stage I-III ER-positive breast cancer from 2001 to 2015 in Surveillance, Epidemiology, and End Results (SEER)-Medicare data. Patients were excluded if they received surgery, radiation, chemotherapy, or other targeted drug treatment including anti-HER2 agents. Two Cox proportional-hazards models were constructed to determine the predictors of breast cancer-specific survival and overall survival after a cancer diagnosis. RESULTS: A total of 552 patients were identified, with 82.1% of the patients being 80 years or older and 81.7% of patients being non-Hispanic White. PR positive (OR 1.77; 95% CI 1.09-2.85; p = 0.025) and tumor size larger than 50 mm (OR 1.99; 95% CI 1.05-3.75; p = 0.035) were associated with higher adherence to endocrine therapy. In the multivariable Cox analyses, patients who were adherent of endocrine therapy had significantly worse survival (HR 1.40; 95% CI 1.17-1.69; p < 0.001). The other two factors associated with worse survival were larger tumor size and more comorbidities. The competing risk model demonstrated no statistically significant difference between patients who were adherent to endocrine therapy and those who were not in terms of risk of dying from breast cancer. CONCLUSION: In elderly women with localized ER-positive breast cancer, there were no statistically significant differences in breast cancer-specific or overall mortality between those who were adherent to endocrine therapy and those who were not.