Regenerative Signatures in Bronchioalveolar Lavage of Acute Respiratory Distress Syndrome.

Background: In patients with severe acute respiratory distress syndrome (ARDS) associated with sepsis, lung recovery is considerably delayed, and mortality is much high. More insight into the process of lung regeneration in ARDS patients is needed. Exosomes are important cargos for intercellular communication by serving as autocrine and/or paracrine. Cutting-edge exomics (exosomal proteomics) makes it possible to study the mechanisms of re-alveolarization in ARDS lungs. Aims: This study aimed to identify potential regenerative niches by characterizing differentially expressed proteins in the exosomes of bronchioalveolar lavage (BAL) in ARDS patients. Methods: We purified exosomes from BAL samples collected from ARDS patients by NIH-supported ALTA and SPIROMICS trials. The abundance of exosomal proteins/peptides was quantified using liquid chromatography-mass spectrometry (LC-MS). Differentially expressed exosomal proteins between healthy controls and ARDS patients were profiled for functional annotations, cell origins, signaling pathways, networks, and clinical correlations. Results: Our results show that more exosomal proteins were identified in the lungs of late-stage ARDS patients. Immune cells and lung epithelial stem cells were major contributors to BAL exosomes in addition to those from other organs. We enriched a wide range of functions, stem cell signals, growth factors, and immune niches in both mild and severe patients. The differentially expressed proteins that we identified were associated with key clinical variables. The severity-associated differences in protein-protein interaction, RNA crosstalk, and epigenetic network were observed between mild and severe groups. Moreover, alveolar type 2 epithelial cells could serve as both exosome donors and recipients via autocrine and paracrine mechanisms. Conclusions: This study identifies novel exosomal proteins associated with diverse functions, signaling pathways, and cell origins in ARDS lavage samples. These differentiated proteins may serve as regenerative niches for re-alveolarization in injured lungs.

Correlates of COVID-19 Vaccine Acceptance and Hesitancy in Rural Communities in Western Kenya.

Vaccine hesitancy is a significant global public health concern. This study sought to determine the correlates of acceptance and hesitancy regarding COVID-19 vaccines in rural populations of selected counties in Western Kenya and assess the strategies that can be used to improve COVID-19 vaccine acceptance in Kenya. The study used a quantitative research strategy with a sample of 806 individuals in the Kisumu, Vihiga, and Kakamega counties. Descriptive statistics, correlations and regression analyses were used. Of the 806 study participants, 55% were males and 45% females. Vaccine acceptance was significantly associated with being a male (AOR: 1.46, 95% CI: 1.24-1.59, p < 0.031), having no formal education (AOR: 2.25, 95% CI: 1.16-4.40, p < 0.02), working in the private sector (AOR: 5.78, 95% CI: 3.28-10.88 p < 0.02), and have low income (KES 0-999 (USD 0-9.16)), (AOR: 2.35, 95% CI: 1.13-3.47, p < 0.02). Conclusions: The current study suggests that male gender, no formal education, working in the private sector, and low income KES 0-999 (USD 0-9.6) are significant factors influencing awareness of and possible acceptance of COVID-19 vaccination.

Inter-Examiner Agreement of the National Upper Cervical Chiropractic Association Analysis of the Atlas Subluxation Complex in a 3-View Upper Cervical Radiographic Series.

Objective: The purpose of this study was to measure the inter-examiner agreement between radiograph markings of 2 National Upper Cervical Chiropractic Association board-certified chiropractors. Methods: Two chiropractic examiners who had standardized training marked and analyzed 254 conventional orthogonal radiographic film sets. The level of agreement and potential biases in their measurements were assessed using intraclass correlation coefficients for absolute agreement and Bland-Altman plot analyses. Results: There was 96.1% agreement between the examiners in the measurements of the side of atlas laterality and 94.5% for atlas rotation. The intraclass correlation coefficient was 0.95 (95% CI, 0.93-0.96) for atlas laterality and 0.92 (95% CI, 0.89-0.94) for atlas rotation. The mean difference in the measurement between the 2 examiners was -0.11, P = .12 for atlas laterality and 0.05, P = .55 for atlas rotation. Neither atlas laterality nor atlas rotation measurements were significantly different from zero. Bland-Altman plots were not suggestive of any proportional biases in the 2 measurements. Conclusion: Results of this study show almost perfect agreement between 2 trained chiropractic examiners, with no apparent proportional bias in the analysis of conventional orthogonal radiographic film sets.

Improving Crew Overboard Recovery for Commercial Fishing in the Gulf of Mexico.

Occupational fatality rates in the commercial fishing industry in the United States remain more than 20 times higher than the national average. The burden of commercial fishing fatalities due to unintentional falls overboard is highest in the Gulf of Mexico (GOM) shrimp fishery. The objective of this quasi-experimental, pre-/post-test project design was disseminating recovery slings to GOM captains/deckhands, training in their use, and assessing the attitudes, beliefs, and intentions of fishermen in their adoption. Due to the COVID-19 pandemic, a land-based simulation was used to train commercial fishermen at three port locations in use of crew overboard (COB) recovery slings. A survey was developed to assess the attitudes, beliefs, and intentions of commercial fishermen in COB recovery. Purposive sampling was employed to recruit 30-50 fishermen at each location. Following pre-/post-training surveys, fishermen received one recovery sling per vessel along with a task list of instructions for use of the sling. A third survey and task list questions were performed at 12-18 months. There were 119 recovery slings and training in their use provided to 123 commercial shrimp fishing vessel owners/captains and deckhands along the Texas and Louisiana Gulf Coast. Repeated measures analysis of variance of the three surveys showed that positive change in normative beliefs was significant for the importance of quickly and safely maneuvering the vessel to the crew member. This change was most significant over the period from the initial training and receipt of the recovery sling by the vessel captain/deckhand, to the time of follow-up 12-18 months later (p = .03). Regarding control beliefs, training was associated with immediate statistically significant improved confidence that, with assistance, the fisherman would be able to use the sling and other equipment to hoist the COB (p = .02). However, this confidence waned significantly over time (p = .03). Attitudes and beliefs of commercial fishermen in the GOM can be favorably influenced toward a COB recovery device, as well as their confidence, and intention to use such devices. However, results show that attitudes and beliefs may wane over time, emphasizing the importance of repeated training and survival drills in this industry.

COVID-19 Infectious Disease Prevention and Mitigation Practices by Chiropractic Physicians and Licensed Massage Therapists in Mississippi: A Needs Assessment to Inform Health Education and Promotion.

Objective: The purpose of this study was to assess self-reported infection prevention processes and their effect on businesses of chiropractic doctors (DCs) and licensed massage therapists (LMTs) in Mississippi during the COVID-19 pandemic. Methods: We developed a survey that was electronically delivered to all licensed DCs and LMTs in Mississippi between August and September 2020. Assessments were made using Qualtrics software, with data management and subsequent analysis including Pearson's χ2 test. Results: Responses were based on 32 of 323 DCs and 69 of 934 LMTs that were still seeing patients through the pandemic (n = 101, response rate 8%). The DC and LMT practitioners (94%) used treatment table and/or surface sanitizing (91.8%) and hand washing and/or sanitizing (89.8%) between all patients. Female practitioners reported practicing handwashing for at least 20 seconds, whereas male practitioners reported practicing handwashing for at least 15 seconds (P < .001). DCs were more likely to report using gloves for personal protective equipment, and LMTs were more likely to report using face masks (P < .001). Other COVID-19 procedures included limiting practice to acute care (82.5%), checking all patient temperatures (62.9%), sign-in and wait in the car (53.2% LMT vs 6.5% DC, P < .001), and prohibiting all nonpatient visitors (87.7% LMTs vs 9.4% DCs, P < .001). DCs (96.9%) and LMTs (89.9%) reported making referrals for COVID-19 testing or treatment when indicated. LMTs (82.3%) reported seeing fewer patients (P = .03), and older practitioners reported the most economic impact (P = .003) by the pandemic. Patient concerns and LMTs needing more time to perform infection control (P = .04) were reasons cited by practitioners for the reduced number of visits seen. Conclusion: Most respondents had moderate to high compliance with guidelines on recommended infection prevention processes during fall 2020 of the COVID-19 pandemic. This assessment of compliance may be used to help guide future health education and promotion research of disease prevention and mitigation as well as physical and economic burdens faced by DCs and LMTs in Mississippi during a pandemic.

Clinicopathologic significance and race-specific prognostic association of MYB overexpression in ovarian cancer.

Late diagnosis, unreliable prognostic assessment, and poorly-guided therapeutic planning result in dismal survival of ovarian cancer (OC) patients. Therefore, identifying novel functional biomarker(s) is highly desired for improved clinical management. MYB is an oncogenic transcription factor with emerging functional significance in OC. Here we examined its clinicopathologic significance by immunohistochemistry and TCGA/GTex data analyses. Aberrant MYB expression was detected in 94% of OC cases (n = 373), but not in the normal ovarian tissues (n = 23). MYB was overexpressed in all major epithelial OC histological subtypes exhibiting the highest incidence (~ 97%) and overall expression in serous and mucinous carcinomas. MYB expression correlated positively with tumor grades and stages. Moreover, MYB exhibited race-specific prognostic association. Moderate-to-high MYB levels were significantly associated with both poor overall- (p = 0.02) and progression-free (p = 0.02) survival in African American (AA), but not in the Caucasian American (CA) patients. Consistent with immunohistochemistry data, we observed significantly higher MYB transcripts in OC cases (n = 426) than normal ovary (n = 88). MYB transcripts were significantly higher in all epithelial OC subtypes, compared to normal, and its greater levels predicted poor survival in AA OC, but not CA OC, patients. Thus, MYB appears to be a useful clinical biomarker for prognostication, especially in AA patients.

Anti-Inflammatory Treatment of COVID-19 Pneumonia With Tofacitinib Alone or in Combination With Dexamethasone is Safe and Possibly Superior to Dexamethasone as a Single Agent in a Predominantly African American Cohort.

OBJECTIVE: To explore the survival benefit of tofacitinib in addition to dexamethasone in hospitalized patients treated for coronavirus disease 2019 (COVID-19)-related pneumonia. PATIENTS AND METHODS: This is a single-center retrospective observational study. All patients who were hospitalized at Delta Regional Medical Center (a regional hospital in the Mississippi Delta) with a COVID-19 diagnosis and discharged between March 1 and September 30, 2020, are included. The primary outcome was in-hospital mortality in relation to receipt of tofacitinib alone or in addition to dexamethasone (designated as the tofacitinib group), versus dexamethasone alone (designated as the dexamethasone group). RESULTS: Of 269 eligible patients, 138 (51.3%) received tofacitinib uniformly and 131 (48.7%) patients received dexamethasone without tofacitinib. A total of 44 patients expired: 14 (31.8%) in the tofacitinib group and 30 (68.2%) in the dexamethasone group. The proportions of death among the tofacitinib and dexamethasone groups were, respectively, 10.1% and 22.9%. This represents a 70% reduction in odds of dying among the tofacitinib group compared to the dexamethasone group after adjusting for age and clinical parameters captured at hospitalization (adjusted odds ratio: 0.30; 95% CI: 0.12 to 0.76; P=.01). CONCLUSION: The in-patient treatment of COVID-19 pneumonia has rapidly evolved. The addition of dexamethasone has made a relevant improvement on survival. Other immunomodulators have yet to show an impact. Here we present the potential survival benefit of the Janus kinase-signal transducer and activator of transcription inhibitor tofacitinib on COVID-19 pneumonia. We found that adding tofacitinib-based anti-inflammatory therapy to a treatment regimen including dexamethasone in COVID-19 pneumonia seems to have potential benefit of improving survival when compared to dexamethasone alone.

Pulmonary fate and consequences of transferrin-functionalized gold nanoparticles.

Surface functionalization of nanoparticles (NPs) may alter their biological interactions such as uptake by alveolar macrophages (AMs). Pulmonary delivery of gold NPs (Au NPs) has theranostic potential due to their optoelectronic properties, minimal alveoli to blood translocation, and possibility of specific cell targeting. Here, we examined whether coating Au NPs with transferrin alters their protein corona, uptake by macrophages, and pulmonary translocation. Methods: Rats were intratracheally instilled with transferrin-coated Au NPs (Tf-Au NPs) or polyethylene glycol-coated Au NPs (PEG-Au NPs). AMs were collected and processed for quantitation of Au cell uptake using ICP-MS and electron microscopy. Au retention in the lungs and other organs was also determined. The uptake of fluorescently labeled Tf-Au NPs and PEG-Au NPs by monocyte-derived human macrophages was also evaluated in vitro. Results: We showed that Tf-Au NPs were endocytosed by AMs and were retained in the lungs to a greater extent than PEG-Au NPs. Both Au NPs acquired similar protein coronas after incubation in rat broncho-alveolar lavage fluid (BALf). The translocation of Au from both NPs to other organs was less than 0.5% of the instilled dose. Transferrin coating enhanced the uptake of Au NPs by primary monocyte-derived human macrophages. Conclusions: We report that coating of NP surface with transferrin can target them to rat AMs and human monocyte-derived macrophages. NP functionalization with transferrin may enhance NP-based therapeutic strategies for lung diseases.

Burnout and Anxiety Among Trauma Nursing Specialties in a Rural Level I Trauma Center.

BACKGROUND: Burnout and anxiety compromise physical and mental well-being of nurses and jeopardize patient safety. Personal, professional, and workplace characteristics have been associated with burnout and anxiety across diverse practice settings, yet none in rural, community trauma centers. We sought to identify the severity and predictors of burnout and anxiety in the trauma nursing staff of a rural Level I trauma center. METHODS: A convenience sample of trauma nurses from the emergency department (ED), intensive care unit (ICU), and trauma ward was voluntarily surveyed using a demographic questionnaire, the Maslach Burnout Inventory (MBI) subscales: depersonalization (DP), emotional exhaustion (EE), and reduced personal accomplishment, as well as the Generalized Anxiety Disorder seven-item (GAD-7) scale. Multivariable linear regression identified the significant predictors of burnout and anxiety. RESULTS: Ninety-six nurses completed surveys (response rate: 83.5%). Married or divorced status, and ICU or trauma ward job assignments were associated with significantly lower adjusted DP scores. Thus, the model-predicted score for a single ED nurse was 15 versus a predicted score of 7 for a divorced ICU or trauma ward nurse, p < .001 for each group. The GAD-7 model demonstrated that race/ethnicity (Asian compared with White, coefficient: -5.06, p = .03), number of children (2 compared with 0, coefficient: -2.54, p = .02), and job tenure (5-10 years vs. <2, coefficient: -3.18, p = .01) were each associated with fewer GAD-7 points. CONCLUSION: Depersonalization and anxiety vary across the trauma nursing workforce based on identifiable personal and work-related risk factors. Group-specific, targeted interventions are needed to effectively reduce burnout and anxiety in trauma nursing staff.

Therapeutic Use of Acetaminophen and Light to Moderate Alcohol: Are There Early Disparate Risks for Kidney Disease?

Introduction: Acetaminophen (APAP) is the most common medication taken in the United States. Using the 2003-2004 U.S. National Health and Nutrition Examination Survey (NHANES), the authors previously explored and reported the relationship of concomitant consumption of light to moderate alcohol (LMA) and therapeutic doses of APAP to early risk of renal dysfunction among adults in the United States. Statistically significant increased odds of renal dysfunction were noted among respondents who reported use of therapeutic doses of APAP and LMA by adjusting for hypertension, diabetes, and obesity. In this study the authors explored further on of potential disparities in the above relationship in the population. The relationship was verified with the 2009 Chronic Kidney Disease-Epidemiology Collaboration creatine-based estimated Glomerular Filtration Rate (GFR). Methods: Subgroup logistic regression analyses to assess disparities based on gender, race, age, education, and income were performed for renal dysfunction measured in terms of serum creatinine (SCr) directly as well as self-report using NHANES 2003-2004 data. Results: Early stage renal dysfunction, as determined by self-reports, and SCr and GFR values may occur among those who concomitantly ingested therapeutic doses of APAP and described alcohol use when compared to those who do not. Risks were more profound among females, particularly in minority racial groups, below legal drinking age of 21, and with household income below $25K. Conclusion: Potential risks for renal dysfunction are apparent in a disparate manner resulting in possible health inequity. Further research could increase the sample size of minority groups and specifically assess for effect modifiers that NHANES does not include for assessment.

Racial Variation in the Relationship of Glycemic Control with Fracture Risk in Elderly Patients with Diabetes.

We investigated racial variation in glycemic control (glycated hemoglobin A1c [HbA1c]) with fracture risk in geriatric patients with diabetes. Compared to an HbA1c of 7.0-7.9% [53-63 mmol/mol], HbA1c ≥9.0% [≥75 mmol/mol] was associated with increased fracture risk among Blacks and those of Unknown race only. This increase was attenuated in Blacks after accounting for the relative frequency of patient-provider interaction.

Assessing Adverse Events After Chiropractic Care at a Chiropractic Teaching Clinic: An Active-Surveillance Pilot Study.

OBJECTIVE: This study aimed to assess the feasibility of implementing an active-surveillance reporting system within a chiropractic teaching clinic and subsequently determining the frequency of adverse events (AEs) after treatment administered by chiropractic interns. METHODS: Interns were invited to collect data from patients using 3 questionnaires that recorded patient symptom change: 2 completed by the patient (before and 7 days after treatment) and 1 completed by the intern (immediately after treatment). Worsened and new symptoms were considered AEs. Qualitative interviews were conducted with clinicians and interns to assess the feasibility of implementing the reporting system, with resulting data categorized under 4 domains: acceptability, implementation, practicality, and integration. RESULTS: Of the 174 eligible interns, 80 (46.0%) collected data from 364 patient encounters, with 119 (32.7%) returning their posttreatment form. Of the 89 unique patients (mean age = 39.5 years; 58.4% female, 41.6% male), 40.1% presented with low back pain and 31.1% with neck pain. After treatment, 25 symptoms (8.9%) were identified as AEs, mostly reported by patients as worsening discomfort or pain. Data from qualitative interviews suggest that the AE reporting system was well accepted; however, proposed specific modifications include use of longitudinal electronic surveys. CONCLUSION: Our findings suggest that it is feasible to conduct an active-surveillance reporting system at a chiropractic teaching clinic. Important barriers and facilitators were identified and will be used to inform future work regarding patient safety education and research.

Author Correction: Cancer Testis Antigen Promotes Triple Negative Breast Cancer Metastasis and is Traceable in the Circulating Extracellular Vesicles.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Potential predictors of hospital length of stay and hospital charges among patients with all-terrain vehicle injuries in rural Northeast Texas.

BACKGROUND: All-Terrain Vehicles (ATVs) have become popular for recreation use in recent years. Texas has had more ATV related fatalities than any other state in the nation, with rural Northeast Texas having even higher rates of injuries. There is limited data examining the relationship between ATV injuries and the length of hospital stay, as well as hospital costs. This paper examines both issues in children as well as adults. METHODS: The regional trauma registry was analyzed for all ATV related injuries between January 2011- October 2016. Injury Severity Score, Glasgow Coma Scale and if they are seen at a Level I Trauma center are predictive for both hospital length of stay and charges. RESULTS: Length of Stay was predicted positively by Injury Severity Score, Emergency Department Respiration Rate and facility at which patients were treated and negatively by Glasgow Coma Scale. Hospital charges were predicted positively by age, Injury Severity Score, facility of treatment, means of transportation, and Emergency Department pulse and negatively by Glasgow Coma Scale. CONCLUSIONS: The study found that vital signs can be useful in predicting length of stay and hospital charges. This study not only confirms the findings of other studies regarding what predictors can be used, but expands the research into rural traumatic injuries. It is hoped that this data can help contribute to the development of algorithms to predict which patients will be most likely to require resource intensive treatment.

Cervical Cancer Prevention in Racially Disparate Rural Populations.

Background: Undergoing a timely Pap smear, high-risk human papilloma virus (HPV)- and colposcopy-based testing can reduce HPV-associated cervical cancer (CC) development in women. However, in rural areas, women and minorities without insurance do not undergo periodic assessment and remain at greater risk of HPV infection and CC. Methods: In this study, 173 women from rural East Texas with various ethnic backgrounds were examined thorough HPV/Pap-based testing and colposcopic assessment. Results: Of the 113 informative cases, 77% (87/113) were positive for high-risk HPV infection and 23% of subjects (26/113) were negative. Associations between HPV positivity with young age (p = 0.002), and a low number of pregnancy (p = 0.004) and births (p = 0.005) were evident. Women with long-term use of contraceptives (OR 1.93, 95% CI, 0.80-4.69) were associated with increased risk of HPV infection. African-American women had a higher risk of abnormal Pap outcome compared to Caucasians (OR 5.31, 95% CI, 0.67-42.0). HPV seemed to be a predictor of abnormal Pap outcome (OR 1.77, 95% CI, 0.48-6.44) in these subjects. Unmarried/widowed/divorced women had an increased abnormal Pap test outcome compared to married women or women living with a partner (p = 0.01), with over 278% increased odds (OR 3.78 at 95% CI, 1.29-11.10). Insured women undergoing periodic checkups were detected early with high-risk HPV infection and abnormal Pap test/colposcopic outcome. Conclusions: Comprehensive and timely screening of uninsured women and minorities in rural East Texas are warranted, which could potentially prevent the onset of HPV-associated CC.

Cancer Testis Antigen Promotes Triple Negative Breast Cancer Metastasis and is Traceable in the Circulating Extracellular Vesicles.

Triple negative breast cancer (TNBC) has poor survival, exhibits rapid metastases, lacks targeted therapies and reliable prognostic markers. Here, we examined metastasis promoting role of cancer testis antigen SPANXB1 in TNBC and its utility as a therapeutic target and prognostic biomarker. Expression pattern of SPANXB1 was determined using matched primary cancer, lymph node metastatic tissues and circulating small extracellular vesicles (sEVs). cDNA microarray analysis of TNBC cells stably integrated with a metastasis suppressor SH3GL2 identified SPANXB1 as a potential target gene. TNBC cells overexpressing SH3GL2 exhibited decreased levels of both SPANXB1 mRNA and protein. Silencing of SPANXB1 reduced migration, invasion and reactive oxygen species production of TNBC cells. SPANXB1 depletion augmented SH3GL2 expression and decreased RAC-1, FAK, A-Actinin and Vinculin expression. Phenotypic and molecular changes were reversed upon SPANXB1 re-expression. SPANXB1 overexpressing breast cancer cells with an enhanced SPANXB1:SH3GL2 ratio achieved pulmonary metastasis within 5 weeks, whereas controls cells failed to do so. Altered expression of SPANXB1 was detected in the sEVs of SPANXB1 transduced cells. Exclusive expression of SPANXB1 was traceable in circulating sEVs, which was associated with TNBC progression. SPANXB1 represents a novel and ideal therapeutic target for blocking TNBC metastases due to its unique expression pattern and may function as an EV based prognostic marker to improve TNBC survival. Uniquely restricted expression of SPANXB1 in TNBCs, makes it an ideal candidate for targeted therapeutics and prognostication.

Reproductive factors and breast cancer risk: A meta-analysis of case-control studies in Indian women.

BACKGROUND/OBJECTIVE: India is the world's most biodiverse region and is undergoing a period of dramatic social and economic change. Due to population's explosion, climate change and lax implementation of environmental policies, the incidence of breast cancer is increasing. From population-based cancer registry data, breast cancer is the most common cancer in women in urban registries where it constitutes more than 30% of all cancers in females. We conducted a meta-analysis of all breast cancer case-control studies conducted in India during 1991-2018 to find pooled estimates of odds ratio (OR). MATERIALS AND METHODS: Eligible studies were identified through a comprehensive literature search of PubMed, EMBASE, and HINARI databases from 1991 to January 2018. This analysis included 24 observational studies out of 34 that reported the case-control distribution of reproductive factors, body mass index (BMI) and type of residence. The analysis was performed using RevMan 5.3 (Review Manager, 2017) applying the random-effects model. RESULTS: A total of 21,511 patients (9889 cases and 11,622 controls) were analyzed, resulting in statistically significant association between breast cancer and the following reproductive factors: never breastfeed (OR: 3.69; 95% confidence interval [CI]: 1.70, 8.01), menopausal age >50 years (OR: 2.88; 95% CI: 1.85, 3.85), menarche age <13 years (OR: 1.83; 95% CI: 1.34, 2.51), null parity (OR: 1.58; 95% CI: 1.21, 2.06), postmenopause (OR: 1.35; 95% CI: 1.13, 1.62), and age at the 1st pregnancy >25 years (OR: 1.57; 95% CI: 1.37, 1.80). Family history (FH) of breast cancer (OR: 5.33; 95% CI: 2.89, 9.82), obesity (OR: 1.19; 95% CI: 1.00, 1.42), and urban residence (OR: 1.22; 95% CI: 1.03, 1.44) were also found to be significant risk factors. CONCLUSION: The results of this meta-analysis are indicative of significant associations between reproductive factors and breast cancer risk, profoundly so among women experiencing menopause after the age of 50, women who never breastfeed and FH of breast cancer.

Phase 1 trial of intrapleural LTI-01; single chain urokinase in complicated parapneumonic effusions or empyema.

BACKGROUND: Current dosing of intrapleural fibrinolytic therapy (IPFT) in adults with complicated parapneumonic effusion (CPE) / empyema is empiric, as dose-escalation trials have not previously been conducted. We hypothesized that LTI-01 (scuPA), which is relatively resistant to PA inhibitor-1 (PAI-1), would be well-tolerated. METHODS: This was an open-label, dose-escalation trial of LTI-01 IPFT at 50,000-800,000 IU daily for up to 3 days in adults with loculated CPE/empyema and failed pleural drainage. The primary objective was to evaluate safety and tolerability, and secondary objectives included assessments of processing and bioactivity of scuPA in blood and pleural fluid (PF), and early efficacy. RESULTS: LTI-01 was well tolerated with no bleeding, treatment-emergent adverse events or surgical referrals (n=14 subjects). uPA antigen increased in PFs at 3 hours after LTI-01 (p<0.01) but not in plasma. PF saturated active PAI-1, generated PAI-1-resistant bioactive complexes, increased PA and fibrinolytic activities and D-dimers. There was no systemic fibrinogenolysis, nor increments in plasma D-dimer. Decreased pleural opacities occurred in all but one subject. Both subjects receiving 800,000 IU required two doses to relieve pleural sepsis, with two other subjects similarly responding at lower doses. CONCLUSION: LTI-01 IPFT was well-tolerated at these doses with no safety concerns. Bioactivity of LTI-01 IPFT was confirmed, limited to PFs where its processing simulated that previously reported in preclinical studies. Preliminary efficacy signals including reduction of pleural opacity were observed.

The effects of a single session of chiropractic care on strength, cortical drive, and spinal excitability in stroke patients.

The objective of this study was to investigate whether a single session of chiropractic care could increase strength in weak plantar flexor muscles in chronic stroke patients. Maximum voluntary contractions (strength) of the plantar flexors, soleus evoked V-waves (cortical drive), and H-reflexes were recorded in 12 chronic stroke patients, with plantar flexor muscle weakness, using a randomized controlled crossover design. Outcomes were assessed pre and post a chiropractic care intervention and a passive movement control. Repeated measures ANOVA was used to asses within and between group differences. Significance was set at p < 0.05. Following the chiropractic care intervention there was a significant increase in strength (F (1,11) = 14.49, p = 0.002; avg 64.2 ± 77.7%) and V-wave/Mmax ratio (F(1,11) = 9.67, p = 0.009; avg 54.0 ± 65.2%) compared to the control intervention. There was a significant strength decrease of 26.4 ± 15.5% (p = 0.001) after the control intervention. There were no other significant differences. Plantar flexor muscle strength increased in chronic stroke patients after a single session of chiropractic care. An increase in V-wave amplitude combined with no significant changes in H-reflex parameters suggests this increased strength is likely modulated at a supraspinal level. Further research is required to investigate the longer term and potential functional effects of chiropractic care in stroke recovery.

Light to moderate drinking and therapeutic doses of acetaminophen: An assessment of risks for renal dysfunction.

This study investigated the potential effect of therapeutic doses of acetaminophen (APAP) in combination with light-moderate amounts of alcohol on kidney functions controlling for factors such as hypertension, diabetes and obesity that may predispose the kidney to APAP and/or alcohol toxicity. Secondary analysis of the 2003-2004 National Health and Nutrition Examination Survey data was performed using SAS 9.4. Odds ratios (OR) and 95% confidence intervals (CI) comparing the likelihood that individuals who ingested therapeutic doses of APAP and light-moderate amount of alcohol, compared to those who did not, would have kidney dysfunction were generated from multiple logistics regression models by further controlling for potential predisposing factors namely hypertension, diabetes and obesity. Kidney dysfunction was defined based on self-reports and laboratory examination of serum creatinine (SCr), blood urea nitrogen (BUN), glomerular filtration rate (GFR) and albumin creatinine ratio (ABCR). Statistically significant increased odds of renal dysfunction were noted among respondents who reported use of therapeutic doses of APAP and light-moderate amount of alcohol [OR(95% CI) = 1.64(1.28-2.10) self-report, 2.18(1.81-2.63) SCr, 4.60(3.03-7.00) BUN, 3.14(2.42-4.07) GFR, and 1.71(1.36-2.14) ALBCR)] even after adjusting for hypertension, diabetes and obesity [Adjusted OR (95% CI) = 1.78 (1.22-2.58) self-report, 2.05 (1.07-3.92) GFR]. The toxic effects of APAP and alcohol on the kidney were hypothesized. The threshold doses at which these effects begin to occur are unknown. The findings of this study suggest that even therapeutic doses of APAP and light-moderate amount of alcohol could be health problematic if consumed concomitantly.