Within the vulnerable time period between injuries, rmTBI produces long-term cognitive deficits independent of increased amyloid β or tau phosphorylation. In this model, cognitive outcome is not influenced by APOE4 status. The data have implications for the long-term mental health of athletes who suffer multiple concussions.

Radiation therapy dose escalation using stereotactic body radiation therapy may significantly improve both local control (LC) and overall survival (OS) for patients with inoperable pancreas cancer. However, ablative dose cannot be routinely offered because of the risk of causing severe injury to adjacent normal organs. Stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) represents a novel technique that may achieve safe delivery of ablative dose and improve long-term outcomes. Methods and Materials: We performed a single institution retrospective analysis of 35 consecutive pancreatic cancer patients treated with SMART in mid-inspiration breath hold on an MR-linear accelerator. Most had locally advanced disease (80%) and received induction chemotherapy (91.4%) for a median 3.9 months before stereotactic body radiation therapy. All were prescribed 5 fractions delivered in consecutive days to a median total dose of 50 Gy (BED 10 100 Gy 10), typically with a 120% to 130% hotspot. Elective nodal irradiation was delivered to 20 (57.1%) patients. No patient had fiducial markers placed and all were treated with continuous intrafraction MR visualization and automatic beam triggering. Results: With median follow-up of 10.3 months from SMART, acute (2.9%) and late (2.9%) grade 3 toxicities were uncommon. Oneyear LC, distant metastasis-free survival, progression-free survival, cause-specific survival, and OS were 87.8%, 63.1%, 52.4%, 77.6%, and 58.9%, respectively.

Megaplasmids in Campylobacter spp. likely play important roles in antibiotic resistance, virulence, and horizontal gene transfer. In this study, megaplasmids pCJDM202 (119 kb) and pCJDM67L (116 kb) from C. jejuni strains WP2-202 and OD2-67, respectively, were sequenced and characterized. These megaplasmids contained genes for tetracycline resistance [tet(O)], the Type IV secretion system, conjugative transfer and the Type VI secretion system (T6SS). The T6SS genes in Campylobacter plasmids encoded genes and proteins that were similar to those identified in Campylobacter chromosomal DNA. When the megaplasmid pCJDM202 from C. jejuni WP2-202 was transferred via conjugation to C. jejuni NCTC11168 Nal + , transconconjugants acquired tetracycline resistance and enhanced cytotoxicity towards red blood cells. A T6SS mutant of strain WP2-202 was generated and designated Δhcp3; the mutant was significantly impaired in its ability to lyse red blood cells and survive in defibrinated blood. The cytotoxicity of Campylobacter strains towards the human embryonic kidney cell line HEK 293 was not impacted by the T6SS. In summary, the T6SS encoded by Campylobacter megaplasmids mediates lysis of RBcs and likely contributes to survival on retail meats where blood cells are abundant. The high prevalence of Campylobacter spp. in retail chicken products is associated with campylobacteriosis outbreaks worldwide 1 and reflects the challenges in preventing Campylobacter contamination in retail meat production and storage 2,3. The consumption of undercooked liver dishes prepared from contaminated chicken liver products was responsible for the multistate outbreaks of campylobacteriosis in the USA 4-6. The antimicrobial resistance and virulence genes in Campylobacter have substantially increased the difficulty in controlling campylobacteriosis 7 , and the transmission of drug-resistant foodborne pathogens through livestock, food products and humans creates a huge public health burden 8. Various aspects of Campylobacter contamination, transmission, and pathogenicity remain unexplored 9. The genetic transfer of antimicrobial resistance and virulence genes between organisms in environmental niches is a common route of acquisition by foodborne pathogens 8. Plasmids in foodborne pathogens such as Campylobacter often encode antimicrobial resistance genes such as tetracycline resistance (tetO); furthermore, pVir plasmids in Campylobacter are frequently involved in virulence 10,11. Many Campylobacter plasmid sequences have been deposited in GenBank 12,13 , and these plasmids have been categorized according to size and genomic composition 14. The complete sequences for several C. jejuni megaplasmids are available but the potential role of these genes in virulence and survival is not clear 13. The Type VI secretion system (T6SS) has been identified in diverse species of Gram-negative bacteria and functions to kill competing bacteria via a bacteriophage-like invasion and injection mechanism 15,16. Various foodborne pathogens, including Salmonella spp., ...

ImportanceThe time interval between COVID-19 infection and surgery is a potentially modifiable but understudied risk factor for postoperative complications.ObjectiveTo examine the association between time to surgery after COVID-19 diagnosis and the risk of a composite of major postoperative cardiovascular morbidity events within 30 days of surgery.Design, Setting, and ParticipantsThis single-center, retrospective cohort study was conducted among 3997 adult patients (aged ≥18 years) with a previous diagnosis of COVID-19, as documented by a positive polymerase chain reaction test result, who were undergoing surgery from January 1, 2020, to December 6, 2021. Data were obtained through Structured Query Language access of an existing perioperative data warehouse. Statistical analysis was performed March 29, 2022.ExposureThe time interval between COVID-19 diagnosis and surgery.Main Outcomes and MeasuresThe primary outcome was the composite occurrence of major cardiovascular comorbidity, defined as deep vein thrombosis, pulmonary embolism, cerebrovascular accident, myocardial injury, acute kidney injury, and death within 30 days after surgery, using multivariable logistic regression.ResultsA total of 3997 patients (2223 [55.6%]; median age, 51.3 years [IQR, 35.1-64.4 years]; 667 [16.7%] African American or Black; 2990 [74.8%] White; and 340 [8.5%] other race) were included in the study. The median time from COVID-19 diagnosis to surgery was 98 days (IQR, 30-225 days). Major postoperative adverse cardiovascular events were identified in 485 patients (12.1%). Increased time from COVID-19 diagnosis to surgery was associated with a decreased rate of the composite outcome (adjusted odds ratio, 0.99 [per 10 days]; 95% CI, 0.98-1.00; P = .006). This trend persisted for the 1552 patients who had received at least 1 dose of COVID-19 vaccine (adjusted odds ratio, 0.98 [per 10 days]; 95% CI, 0.97-1.00; P = .04).Conclusions and RelevanceThis study suggests that increased time from COVID-19 diagnosis to surgery was associated with a decreased odds of experiencing major postoperative cardiovascular morbidity. This information should be used to better inform risk-benefit discussions concerning optimal surgical timing and perioperative outcomes for patients with a history of COVID-19 infection.

Introduction: Proton beam therapy (PBT) reduces normal organ dose compared to intensity-modulated radiation therapy (IMRT) for patients with major salivary gland tumors. It is not known whether this dosimetric advantage is clinically meaningful for reducing acute toxicity. Methods: We evaluated treatment parameters and acute toxicity outcomes of patients with major salivary gland cancers enrolled on the Proton Collaborative Group REG001-09 trial (NCT01255748). Results: One-hundred and five patients with a median age of 61 years were included. The majority had parotid (N ¼ 90) versus submandibular gland (N ¼ 15) tumors. The patients were treated across seven institutions in the United States between 2010 and 2017, most commonly in the postoperative setting (70.5%) although a minority were treated definitively (29.5%). Median PBT dose was 66.5 GyE in 33 fractions; only one patient was prescribed less than 50 GyE. Chemotherapy was given concurrently to 20%. Median follow-up was 14.3 months. Acute grade 2 or higher toxicity included nausea (1.5%), dysgeusia (4.8%), xerostomia (7.6%), mucositis (10.5%) and dysphagia (10.5%). Conclusions: PBT should be strongly considered when ipsilateral radiation therapy is indicated for major salivary gland cancer based on a considerably lower incidence of acute grade 2 or higher toxicity in this analysis compared to historical IMRT outcomes.