Inactivation of multidrug-resistant bacteria and bacterial spores and generation of high-potency bacterial vaccines using ultrashort pulsed lasers.

Multidrug-resistant organisms (MDROs) represent a continuing healthcare crisis with no definitive solution to date. An alternative to antibiotics is the development of therapies and vaccines using biocompatible physical methods such as ultrashort pulsed (USP) lasers, which have previously been shown to inactivate pathogens while minimizing collateral damage to human cells, blood proteins, and vaccine antigens. Here we demonstrate that visible USP laser treatment results in bactericidal effect (≥3-log load reduction) against clinically significant MDROs, including methicillin-resistant Staphylococcus aureus and extended spectrum beta-lactamase-producing Escherichia coli. Bacillus cereus endospores, which are highly resistant to conventional chemical and physical treatments, were also shown to be effectively inactivated by USP laser treatment, resulting in sporicidal (≥3-log load reduction) activity. Furthermore, we demonstrate that administration of USP laser-inactivated E. coli whole-cell vaccines at dosages as low as 105 cfu equivalents without adjuvant was able to protect 100% of mice against subsequent lethal challenge. Our findings open the possibility for application of USP lasers in disinfection of hospital environments, therapy of drug-resistant bacterial infections in skin or bloodstream via pheresis modalities, and in the production of potent bacterial vaccines.

Linguistic and neurocognitive correlates of probabilistic classification learning in schizophrenia.

Individuals with schizophrenia demonstrate impaired implicit learning on cognitively complex tasks and preserved implicit motor learning. However, little is known about how implicit learning may be related to other linguistic and cognitive variables, including development of complex language including comprehension and syntax. This study explored the relationship between probabilistic classification learning, a type of implicit learning style, and linguistic and cognitive skills in schizophrenia. This was done by examining how schizophrenia patients perform on the Weather Prediction Task (WPT) relative to controls, particularly during a dual-task interference condition that assesses task automaticity. Individuals with schizophrenia (N = 34) demonstrated depressed cognitive functioning relative to the controls (N = 18) across nearly all cognitive functions. On the Weather Prediction Task, the schizophrenia group performed less accurately than the control group in later blocks and had a relatively flat learning curve. A significant Group X Block effect when controlling for age and sex suggested differential learning throughout the task. A subgroup of patients did not develop automaticity during the repeated blocks of trials. For those patients who did not develop automaticity over the course of the WPT, linguistic and cognitive skills were strongly correlated with their Block 1 performance. For patients who developed automaticity, overall neurocognitive ability was correlated with their ultimate level of performance on the WPT but not with their Block 1 performance. That language was related to differential learning emphasizes the role of explicit, verbal processes on making initial rapid improvement on the WPT.

Birth outcomes with prescribed chronic and acute opioid exposure during pregnancy.

OBJECTIVES: To assess the effects of no, any, and acute and chronic prescription opioid exposure for pain during pregnancy on maternal and fetal outcomes. DESIGN: Retrospective cohort study. SETTING: Integrated healthcare delivery system. Information on pregnancies and their outcomes were obtained from administrative data and verified via manual chart review. PARTICIPANTS: Women ≥ 18 years of age who were pregnant between January 1, 2012 and May 31, 2015 and had chronic, acute, and no opioid exposure; defined as an ambulatory dispensing(s) of >30 (with a total of 225 morphine equivalents), 1-29, and 0 days supply of opioid, respectively, during pregnancy. MAIN OUTCOME MEASURE: Non-live birth. RESULTS: A total 13,809 pregnancies for 13,131 women were included. Pregnancies with opioid exposure had higher risk scores and more comorbid conditions. A total of 1,319 (9.6 percent) pregnancies had any documented opioid exposure during pregnancy with 125 (1.0 percent) and 1,194 (8.7 percent) pregnancies having had chronic and acute opioid exposure, respectively. Pregnancies with acute opioid exposure had a higher percentage of non-live births (3.1 percent) compared to pregnancies (1.0 percent) with no opioid exposure (adjusted odds ratio = 3.46, 95% confidence interval 2.33-5.14) but no difference compared to pregnancies with chronic (1.6 percent) opioid exposure (p > 0.05 with adjustment). CONCLUSIONS: While a dose response of opioid exposure was not identified, these results add to existing evidence that opioid exposure during pregnancy is correlated with negative outcomes. Practitioners may better serve pregnant women and their fetuses by encouraging alternate pain relief treatments.

A short-form functional capacity evaluation predicts time to recovery but not sustained return-to-work.

OBJECTIVES: To evaluate the ability of a short-form FCE to predict future timely and sustained return-to-work. METHODS: A prospective cohort study was conducted using data collected during a cluster RCT. Subject performance on the items in the short-form FCE was compared to administrative recovery outcomes from a workers' compensation database. Outcomes included days to claim closure, days to time loss benefit suspension and future recurrence (defined as re-opening a closed claim, restarting benefits, or filing a new claim for injury to the same body region). Analysis included multivariable Cox and logistic regression using a risk factor modeling strategy. Potential confounders included age, sex, injury duration, and job attachment status, among others. RESULTS: The sample included 147 compensation claimants with a variety of musculoskeletal injuries. Subjects who demonstrated job demand levels on all FCE items were more likely to have their claims closed (adjusted Hazard Ratio 5.52 (95% Confidence Interval 3.42-8.89), and benefits suspended (adjusted Hazard Ratio 5.45 (95% Confidence Interval 2.73-10.85) over the follow-up year. The proportion of variance explained by the FCE ranged from 18 to 27%. FCE performance was not significantly associated with future recurrence. CONCLUSION: A short-form FCE appears to provide useful information for predicting time to recovery as measured through administrative outcomes, but not injury recurrence. The short-form FCE may be an efficient option for clinicians using FCE in the management of injured workers.