Immediate Teeth in Fibulas Versus Standard Fibula Free Flap: A Comparison of Donor Surgical Site Infections.

BACKGROUND: Immediate placement of dental implants with dental restoration at the leg donor site requires implant components and prosthetic materials that are not packaged sterile. PURPOSE: This study aimed to determine if there was a difference in donor surgical site infection between patients that received a fibula free flap with dental implants and immediate teeth (ITFFF: immediate teeth fibula free flap) before flap transfer to the defect site when compared to standard fibula free flaps (SFFFs) without dental implant placement. STUDY DESIGN, SETTING, SAMPLE: A retrospective cohort study was designed and implemented. The study population was composed of patients who underwent free fibula flap transfer for the treatment of benign or malignant conditions of the head and neck from 2015 to 2022. Patients who received immediate dental implants without teeth were excluded, since those implants are sterile and buried under soft tissue. PREDICTOR VARIABLE: The surgical treatment with either ITFFF or SFFF was treated as the primary predictor variable. MAIN OUTCOME VARIABLE: The primary outcome variable was postoperative donor surgical site infection. COVARIATES: There were 12 covariate variables including age, sex, diabetes diagnosis, immunosuppression/prior chemotherapy treatment, body mass index, smoking status, pack year history, pathology treated, technique for fibula donor site closure, skin paddle harvest, skin paddle area (cm2), and negative pressure wound therapy. ANALYSES: For the effect of the covariates on the primary predictor variable, χ2 analyses and t-tests were used. The effect of the primary predictor variable on the primary outcome was evaluated using χ2 analysis. A P value of < 0.05 was considered statistically significant. RESULTS: There were 37 patients in the ITFFF group and 47 in the SFFF group. The donor site infection rate for the entire study population was 2.38%. In the ITFFF group, there was 1 donor surgical site infection (2.70%), and in the SFFF group there was also 1 donor surgical site infection (2.13%). There was no significant difference in donor surgical site infection between the groups (P = .86). CONCLUSION AND RELEVANCE: This study found no difference in donor surgical site infection rates between patients who received ITFFF versus SFFF. The overall donor surgical site infection rate following fibula free flap is low.

Are More Medically Complex Patients Who Undergo Complex Septorhinoplasty at an Increased Risk for Surgical Site Infection?

BACKGROUND: Prophylactic antibiotics are routinely prescribed by surgeons for their patients who undergo septorhinoplasty. However, the literature to support this remains controversial, especially in complex cases, those that require grafts, revision cases, extended surgical time, and an American Society of Anesthesiologists (ASA) value greater than or equal to 3. PURPOSE: The study purpose was to evaluate for a potential association between increased anesthetic complexity and the risk for surgical site infection (SSI) following complex septorhinoplasty. STUDY DESIGN, SETTING, SAMPLE: Retrospective cohort study of patients who underwent a complex septorhinoplasty between 2005 and 2022 at the Dallas Veterans Affairs Medical Center. Patients were excluded if they did receive a septorhinoplasty, did not follow up, or had insufficient records. INDEPENDENT VARIABLE: All patients were assigned an ASA value prior to surgery, with an ASA value of 3 serving as this study's independent variable. MAIN OUTCOME VARIABLE: The main outcome variable of interest was the development of a postoperative SSI, defined as findings consistent with cellulitis, purulence, or fistula development necessitating antibiotic treatment. COVARIATES: The demographic covariates included patient age and sex. Clinical covariates included diabetes status, history of nasal trauma or surgery, and smoking status. The operative covariates were surgical duration, perioperative antibiotic, intraoperative complication, and type of cartilage graft used. ANALYSES: χ2 Analysis and t-tests were used for calculations, with P values < .05 being considered significant. RESULTS: A total of 182 patients were included in this study, 81 (45%) with an ASA ≤2 and 101 (55%) with an ASA of 3. A patient's age (P < .01), male sex (P < .01), and a diagnosis of diabetes (P < .01) were associated with an ASA value of 3. In total, there were 6 (3.3%) SSIs, with 2 (1%) occurring in those with an ASA of 3. An ASA value of 3 (P = .27, relative risk of .40) was not shown to be associated with an increased risk of SSI. CONCLUSION AND RELEVANCE: Our results suggest that an ASA of 3 is not significant with regard to postoperative infection in patients who undergo a complex nasal septorhinoplasty, and prophylactic postoperative antibiotics are not warranted.

A Conditioned Place Preference for Heroin Is Signaled by Increased Dopamine and Direct Pathway Activity and Decreased Indirect Pathway Activity in the Nucleus Accumbens.

Repeated pairing of a drug with a neutral stimulus, such as a cue or context, leads to the attribution of the drug's reinforcing properties to that stimulus, and exposure to that stimulus in the absence of the drug can elicit drug-seeking. A principal role for the NAc in the response to drug-associated stimuli has been well documented. Direct and indirect pathway medium spiny neurons (dMSNs and iMSNs) have been shown to bidirectionally regulate cue-induced heroin-seeking in rats expressing addiction-like phenotypes, and a shift in NAc activity toward the direct pathway has been shown in mice following cocaine conditioned place preference (CPP). However, how NAc signaling guides heroin CPP, and whether heroin alters the balance of signaling between dMSNs and iMSNs, remains unknown. Moreover, the role of NAc dopamine signaling in heroin reinforcement is unclear. Here, we integrate fiber photometry for in vivo monitoring of dopamine and dMSN/iMSN calcium activity with a heroin CPP procedure in rats to begin to address these questions. We identify a sensitization-like response to heroin in the NAc, with prominent iMSN activity during initial heroin exposure and prominent dMSN activity following repeated heroin exposure. We demonstrate a ramp in dopamine activity, dMSN activation, and iMSN inactivation preceding entry into a heroin-paired context, and a decrease in dopamine activity, dMSN inactivation, and iMSN activation preceding exit from a heroin-paired context. Finally, we show that buprenorphine is sufficient to prevent the development of heroin CPP and reduce Fos activation in the NAc after conditioning. Together, these data support the hypothesis that an imbalance in NAc activity contributes to the development of drug-cue associations that can drive addiction processes.SIGNIFICANCE STATEMENT The attribution of the reinforcing effects of drugs to neutral stimuli (e.g., cues and contexts) contributes to the long-standing nature of addiction, as re-exposure to drug-associated stimuli can reinstate drug-seeking and -taking even after long periods of abstinence. The NAc has an established role in encoding the value of drug-associated stimuli, and dopamine release into the NAc is known to modulate the reinforcing effects of drugs, including heroin. Using fiber photometry, we show that entering a heroin-paired context is driven by dopamine signaling and NAc direct pathway activation, whereas exiting a heroin-paired context is driven by NAc indirect pathway activation. This study provides further insight into the role of NAc microcircuitry in encoding the reinforcing properties of heroin.

How Does Changing the Time to Surgery Affect the Recurrence of Post-Traumatic Trigeminal Neuropathic Pain.

PURPOSE: The recurrence of post-traumatic trigeminal neuropathic pain (PTTNp) following peripheral microneurosurgery continues to be poorly understood. The objective of this study was to determine if the time from injury to surgery of the trigeminal nerve in patients with PTTNp affected the recurrence of PTTNp following surgery. PATIENTS AND METHODS: A retrospective cohort of patients with PTTNp prior to trigeminal nerve surgery at a single institute was analyzed for the presence or absence of PTTNp at 6 months postsurgery. The primary predictor was the time from injury to surgical treatment and the primary outcome was the presence or absence of PTTNp using subjective and objective neurosensory testing at 6 months. Four groups were predefined to evaluate the effect of time to surgery: Group 1 (0 to 100 days), Group 2 (101 to 200 days), Group 3 (201 to 300 days), and Group 4 (> 300 days). Repeated measures analysis of variance was used to assess differences in the presence or absence of PTTNp among groups. If a statistical difference was found, a post hoc Tukey-Kramer test was performed. RESULTS: Sixty of 63 eligible patients met inclusion and exclusion criteria with end points at 6 months. The weighted mean PTTNp score in Group 1 was 1.6 ± 0.32, Group 2 was 1.61 ± 0.18, Group 3 was 1.3 ± 0.29, and Group 4 was 1 ± 0.0. There was a statistically significant difference in the primary outcome among the groups based on time from injury to repair (P = .0002). The between-group differences were significant for Group 1 and 3 and 4 and between Group 2 and 3 and 4 (P < .01). Within the 4 cohorts, the percentage of patients with PTTNp before surgery with no neuropathic pain at the 6-month follow-up was 41.6%. However, between the 4 cohorts, when the time to surgery was 200 days or less, the percentage of patients with PTTNp before surgery with no neuropathic pain at the 6-month follow-up was more than 60%. CONCLUSIONS: Time from injury to surgery appears to have an effect on the recurrence of PTTNp. Best outcomes are associated with operative interventions within 200 days of the injury.

Is Presurgical Pain Intensity Related to Postoperative Recurrence of Post-Traumatic Trigeminal Neuropathic Pain?

PURPOSE: Post-traumatic trigeminal neuropathic pain (PTTNp) is a challenging condition to treat, and equally as challenging is the identification of surgical outcome variables to guide treatment. The study purpose was to determine if preoperative pain intensity was related to postoperative recurrence of PTTNp. MATERIALS AND METHODS: This retrospective cohort study assessed subjects at a single institution with preoperative PTTNp of either the lingual or inferior alveolar nerves who underwent elective microneurosurgery. Two cohorts were established as follows: No PTTNp at 6 months (group 1); presence of PTTNp at 6 months (group 2). The primary predictor variable was the preoperative visual analog scale (VAS) score. The primary outcome variable was PTTNp (recurrence or no recurrence at 6 months). The demographic and injury characteristics of the groups were compared to assess whether they were similar using Wilcoxon rank analysis. Two-tailed Student's t-test was performed to analyze the difference in preoperative mean VAS scores. Multivariate multiple linear regression models were used to determine the association between the covariates on the outcomes of the primary predictor variable and the primary outcome variable. A P value of <.05 was considered statistically significant. RESULTS: Forty-eight patients were included in the final analysis. There were 20 patients with no pain at 6 months and 28 with recurrence at 6 months following surgery. There was a significant difference in mean preoperative pain intensity between the two groups (P value .04). The mean preoperative VAS score in group 1 was 6.31 (standard deviation, 2.65), while the mean preoperative VAS score in group 2 was 7.75 (standard deviation, 1.95). Regression analysis showed that one covariate, the type of nerve injured, explained some variability of preoperative VAS score, but by only 16% (P value .005). Regression analysis also showed that two covariates, Sunderland classification and time to surgery, explained some of the variability of PTTNp at 6 months, by approximately 30% (P value .001). CONCLUSION: This study showed that presurgical pain intensity level was related to postoperative recurrence in the surgical treatment of PTTNp. In patients with recurrence, the preoperative pain intensity was higher. Other factors, including time interval from injury to surgery, were also related to recurrence.

Medication-Related Osteonecrosis of the Jaws in the Pediatric Population.

PURPOSE: Few reports have investigated medication-related osteonecrosis of the jaws (MRONJ) in the pediatric population. The study purpose was to measure the frequency of MRONJ in pediatric patients receiving antiresorptive medications at our institution. MATERIALS AND METHODS: This retrospective case series was granted an exemption by the University of Texas Southwestern Medical Center Institutional Review Board. The primary outcome variable was the presence or absence of MRONJ. Other variables of interest included 1) age at first dose of antiresorptive; 2) sex; 3) antiresorptive medication received; 4) reason for antiresorptive; 5) dental records available; 6) dental extractions that occurred after the start of antiresorptive; 7) exposure to immunosuppressants/chemotherapy; 8) time interval from the last dose of antiresorptive to dental extractions; and 9) longest follow-up after starting antiresorptive. Frequencies and proportions were calculated for categorical data. Medians, means, and standard deviations were calculated for continuous data. RESULTS: The study sample was composed of 122 subjects. We observed 0 cases of MRONJ during the study interval. At the start of antiresorptive treatment, the average age was 8.18 years (range 0.02-17; standard deviation (SD) 5.15). There were 67 males (55%) and 55 females (45%). The reason for antiresorptive treatment was osteogenesis imperfecta in 36 patients, malignancy in 6 patients, and other in 80 patients. Thirty patients received pamidronate, 72 received zoledronate, 17 received a combination, and 3 received only denosumab. A total of 16 patients had exposure to immunosuppressants and/or chemotherapy. The average follow-up time was 4.89 years (median 4 years). Twenty-six patients underwent dental extractions of 74 teeth following antiresorptive treatment. CONCLUSIONS: While there were no reported cases of MRONJ in the present study, it is advisable to monitor pediatric patients who have received antiresorptive treatment closely. When possible, appropriate dental treatment should be completed prior to starting antiresorptive therapy. In the absence of reported MRONJ cases, dental extractions should not be withheld because of previous antiresorptive exposure and antiresorptive medication dosing need not be altered in the pediatric population.

The Cost of Surgically Treated Severe Odontogenic Infections: A Retrospective Study Using Severity Scores.

PURPOSE: Hospital treatment of odontogenic infections can be costly, and often these infections present with varying degrees of severity that can be quantified with odontogenic infection severity scores (OISSs). The purposes of this study were (1) to measure the association between OISSs and hospital bills and (2) to identify risk factors associated with OISSs. METHODS: This retrospective cohort study assessed subjects from January 1, 2016, to December 31, 2020, with severe odontogenic infections treated in the operating room and admitted to the University of Texas Southwestern Medical Center/Parkland Memorial Hospital for >1 hospital day. OISSs were assigned based on the risk to the airway and vital structures. OISSs ≥ 5 were designated group A and < OISSs 5 group B. The primary predictor variable was OISSs, and the primary outcome variable was the mean billed cost of the stay. Analysis to identify associated variables for OISS ≥ 5 was also conducted. Secondary predictor variables were age, gender, smoking status, HIV diagnosis, diabetes mellitus diagnosis, blood glucose at admission, and white blood cell count (WBC) at admission. The secondary outcome variable was OISS. Comparisons between Group A and Group B were conducted using t-tests. Analysis to identify associated variables for OISS ≥ 5 was conducted using univariate and multivariate analysis. Values of P < .05 were considered statistically significant. RESULTS: There were 144 subjects that met inclusion criteria. There were 65 subjects in Group A and 69 in Group B. Group A had a significantly larger mean billed cost of stay (95% CI 8937.7 to 48,225.74; P = .001). Analysis of secondary predictor variables revealed that male sex (OR 2.07; 95% CI 1.06 to 4.07; P = .03), blood glucose ≥ 100 at presentation (OR 3.05; 95% CI 1.46 to 6.38; P = .002), and WBC of > 11,000/mL at presentation (OR 3.17; 95% CI 1.44 to 6.98; P = .003) resulted in an increased likelihood of OISS ≥ 5. CONCLUSIONS: Patients with OISSs ≥ 5 have higher mean billed costs when compared to patients with OISSs < 5. Male sex, blood glucose ≥ 100, and WBC >11,000/mL at presentation is associated with increased likelihood of OISS >5.

Low Insertional Torque and Early Dental Implant Failure.

PURPOSE: There is lack of uniformity regarding the ideal insertional torque with which dental implants need to be placed. The purpose of this retrospective analysis is to compare the incidence of early dental implant failures with an insertional torque less than 30 N-cm to implants placed with an insertional torque 30 N-cm or greater. METHODS: A retrospective cohort study was conducted to evaluate dental implants placed between 2015 and 2016 at the Veterans Affairs North Texas Health Care System in Dallas. The primary predictor variable was dental implant insertional torque, measured at the time of implant placement as either greater than or equal to 30 N-cm or less than 30 N-cm. The primary outcome variable was early implant failure, defined as implant exfoliation noted by the patient or failure due to implant movement or pain necessitating explantation before prosthesis loading. The study conducted a time-to-event analysis to examine a group difference in time to implant failure between insertional torque group greater than or equal to 30 N-cm and less than 30 N-cm using Kaplan-Meir curves and a frailty model. The time to follow-up was censored at 6 months. RESULTS: One hundred three patients had 214 implants placed, with early failures occurring in 14 implants (6.5%). Implants placed with an insertional torque less than 30 N-cm were nearly 14 times more likely to have an early failure compared to implants placed with an insertional torque 30 N-cm or greater (hazard ratio = 13.909; 95% confidence interval, 1.835 to 105.416), which was statistically significant (P = .0108). CONCLUSIONS: The results of this retrospective cohort study suggest that insertional torque values less than 30 N-cm are associated with early dental implant failures. Future, prospective studies will be performed to further elucidate the association between insertional torque and early dental implant failure.

Consumer panic in the COVID-19 pandemic.

We develop an econometric model of consumer panic (or panic buying) during the COVID-19 pandemic. Using Google search data on relevant keywords, we construct a daily index of consumer panic for 54 countries from January 1st to April 30th 2020. We also assemble data on government policy announcements and daily COVID-19 cases for all countries. Our panic index reveals widespread consumer panic in most countries, primarily during March, but with significant variation in the timing and severity of panic between countries. Our model implies that both domestic and world virus transmission contribute significantly to consumer panic. But government policy is also important: Internal movement restrictions - whether announced by domestic or foreign governments - generate substantial short run panic that largely vanishes in a week to ten days. Internal movement restrictions announced early in the pandemic generated more panic than those announced later. Stimulus announcements had smaller impacts, and travel restrictions do not appear to generate consumer panic.

Consensus Recommendations on the Prehospital Care of the Injured Athlete With a Suspected Catastrophic Cervical Spine Injury.

INTRODUCTION: Sports participation is among the leading causes of catastrophic cervical spine injury (CSI) in the United States. Appropriate prehospital care for athletes with suspected CSIs should be available at all levels of sport. The goal of this project was to develop a set of best-practice recommendations appropriate for athletic trainers, emergency responders, sports medicine and emergency physicians, and others engaged in caring for athletes with suspected CSIs. METHODS: A consensus-driven approach (RAND/UCLA method) in combination with a systematic review of the available literature was used to identify key research questions and develop conclusions and recommendations on the prehospital care of the spine-injured athlete. A diverse panel of experts, including members of the National Athletic Trainers' Association, the National Collegiate Athletic Association, and the Sports Institute at UW Medicine participated in 4 Delphi rounds and a 2-day nominal group technique (NGT) meeting. The systematic review involved 2 independent reviewers and 4 rounds of blinded review. RESULTS: The Delphi process identified 8 key questions to be answered by the systematic review. The systematic review comprised 1544 studies, 49 of which were included in the final full-text review. Using the results of the systematic review as a shared evidence base, the NGT meeting created and refined conclusions and recommendations until consensus was achieved. CONCLUSIONS: These conclusions and recommendations represent a pragmatic approach, balancing expert experiences and the available scientific evidence.

Endophthalmitis after penetrating keratoplasty.

PURPOSE: To determine the incidence of endophthalmitis after penetrating keratoplasty (PK) and patient and donor risk factors. DESIGN: Retrospective cohort study using national transplant registry data. PARTICIPANTS: All corneal transplant recipients (n = 11 320) registered on the United Kingdom Transplant Registry undergoing their first PK between April 1999 and December 2006. METHODS: Patients who developed endophthalmitis were identified on the transplant registry. In addition, cases where the fellow cornea from the same donor had been transplanted were included. Clinical information regarding donor and recipient characteristics, surgical details, and postoperative outcomes were collected and analyzed. In cases where endophthalmitis was reported, the diagnosis was verified by a follow-up supplementary questionnaire to the surgeon. Logistic regression was used to investigate differences in the factors associated with the development of endophthalmitis. MAIN OUTCOME MEASURES: Incidence of endophthalmitis and graft survival. RESULTS: The overall incidence of endophthalmitis occurring after primary PK in the UK was 0.67%. The incidence of endophthalmitis occurring within 6 weeks of surgery was 0.16%. Graft survival after endophthalmitis was 27% (95% confidence interval, 16-38) at 5 years, with a mean best-corrected visual acuity of 1.13 (logarithm of the minimum angle of resolution) for surviving grafts. Factors associated with endophthalmitis were donor cause of death (infection), high-risk cases, and indication for corneal transplantation. CONCLUSION: Endophthalmitis remains a serious issue, with those affected having reduced graft survival and poor visual outcomes. Management of the identified recipient and donor risk factors are important to reduce endophthalmitis risk. In particular, the increased incidence of endophthalmitis when the donor dies of infection requires further explanation and review of current donor eye retrieval and eye bank practices. The delayed presentation of endophthalmitis cases also raises questions regarding possible sequestration of microbes within the corneal tissue and the effect of antimicrobials in storage media.

Are higher odontogenic infection severity scores associated with difficult intubations?

PURPOSE: This study aimed to determine if there is a relation between odontogenic infection severity score (OISS) and difficult intubation at the time of surgical treatment for severe odontogenic infections (SOI). A secondary goal of this study was to determine the utility of OISS as a predictor of difficult intubations. METHODS: This retrospective cohort study was composed of consecutive patients admitted and surgically treated in the operating room (OR) for SOIs. Patients with an OISS ≥ 5 were designated as Group 1 and < 5 Group 2. RESULTS: There was a statistically significant difference in difficult intubations between the two groups (p = 0.018). Patients with an OISS ≥ 5 were nearly four times more likely to be difficult intubations compared to patients with an OISS < 5 (OR 3.70, 95% CI 1.19-11.45). When OISS ≥ 5 was used to predict difficult intubation, the sensitivity was 69%, the specificity was 63%, the positive predictive value was 23%, and the negative predictive value was 93%. CONCLUSION: OISS ≥ 5 was associated with a higher prevalence of difficult intubations compared to an OISS < 5. OISS may provide clinically relevant data that can be used with established risk factors, laboratory values, and clinical judgment.

The utility of cone-beam computed tomography and multislice computed tomography scan for the evaluation of invasion versus erosion by mandibular squamous cell carcinoma as viewed on medical PACS.

Introduction: The degree of bone involvement in mandibular squamous cell carcinoma has a significant impact on surgical planning. The purpose of this study was to determine the utility of cone-beam computed tomography (CBCT) for the evaluation of invasion by mandibular squamous cell carcinoma. Methods: A retrospective review was conducted to identify subjects treated for oral squamous cell carcinoma (OSCC). All subjects had OSCC adjacent or fixed to the mandible, received preoperative CBCT and multislice computed tomography scan (MSCT), and had resection specimens that included bone. Results: Twenty-one subjects met the inclusion criteria. The sensitivity of CBCT was 100% (95% CI 0.75-1), the specificity was 75% (95% CI 0.35-0.97), the positive predictive value was 87% (95% CI 0.66-0.98), and the calculated test accuracy was 91%. The sensitivity of MSCT was 92% (95% CI 0.64-1), the specificity was 100% (95% CI 0.63-1), and the calculated test accuracy was 95%. Discussion: CBCT provides meaningful data that may be useful in identifying bony involvement in patients with mandibular squamous cell carcinoma. The utility in delineating erosion versus invasion is limited.

The effect of free flap surgery for oral cancer on laryngeal grade and intubation difficulty.

OBJECTIVE: The purpose of this study was to evaluate the change in laryngeal grade and intubation difficulty at subsequent surgery in patients with prior free flap reconstruction for oral cancer. STUDY DESIGN: This retrospective case series included patients with a diagnosis of oral cancer who underwent free flap reconstruction (FFR) (S1) followed by a subsequent surgery (S2) which required intubation. The primary predictor variable was FFR. The primary outcome variable was the change in laryngeal grade, based on the classification of Cormack and Lehane, after FFR. Secondary outcomes were intubation difficulty and number of intubation attempts. RESULTS: Thirty-three patients were included in the study. At S1, the average laryngeal grade was 1.1. There were 5 difficult intubations. The average time to S2 was 19 months. At S2, average laryngeal grade was 1.4. There were 17 difficult intubations. Analysis showed a significant association between FFR and a more obstructed view of the glottis at S2 (P = .007; 95% CI 0.101-0.808). FFR increased the odds of having >1 intubation attempt nearly 7-fold (OR 6.74; 95% CI 1.35-33.75), and the odds of a difficult intubation nearly 6-fold (OR 5.95; 95% CI 1.84-19.19) at S2, both of which were significant (P = .011 and P = .002, respectively) CONCLUSIONS: This investigation found an association between FFR for patients with oral cancer and a higher laryngeal grade - that is, a more obstructed view of the glottis - at subsequent surgery, in addition to increased intubation difficulty and greater number of intubation attempts.

Valence ambiguity dynamically shapes striatal dopamine heterogeneity.

Adaptive decision making relies on dynamic updating of learned associations where environmental cues come to predict positive and negatively valenced stimuli, such as food or threat. Flexible cue-guided behaviors depend on a network of brain systems, including dopamine signaling in the striatum, which is critical for learning and maintenance of conditioned behaviors. Critically, it remains unclear how dopamine signaling encodes multi-valent, dynamic learning contexts, where positive and negative associations must be rapidly disambiguated. To understand this, we employed a Pavlovian discrimination paradigm, where cues predicting positive and negative outcomes were intermingled during conditioning sessions, and their meaning was serially reversed across training. We found that rats readily distinguished these cues, and updated their behavior rapidly upon valence reversal. Using fiber photometry, we recorded dopamine signaling in three major striatal subregions -,the dorsolateral striatum (DLS), the nucleus accumbens core, and the nucleus accumbens medial shell - and found heterogeneous responses to positive and negative conditioned cues and their predicted outcomes. Valence ambiguity introduced by cue reversal reshaped striatal dopamine on different timelines: nucleus accumbens core and shell signals updated more readily than those in the DLS. Together, these results suggest that striatal dopamine flexibly encodes multi-valent learning contexts, and these signals are dynamically modulated by changing contingencies to resolve ambiguity about the meaning of environmental cues.

Microbial keratitis in Southern Malawi: a microbiological pilot study.

OBJECTIVE: Microbial keratitis (MK) is a significant cause of blindness in sub-Saharan Africa. We investigated the feasibility of using a novel corneal impression membrane (CIM) for obtaining and processing samples by culture, PCR and whole-genome sequencing (WGS) in patients presenting with suspected MK in Malawi. METHODS AND ANALYSIS: Samples were collected from patients presenting with suspected MK using a 12 mm diameter polytetrafluoroethylene CIM disc. Samples were processed using culture and PCR for Acanthamoeba, herpes simplex virus type 1 (HSV-1) and the bacterial 16S rRNA gene. Minimum inhibitory concentrations of isolates to eight antimicrobials were measured using susceptibility strips. WGS was used to characterise Staphylococcus aureus isolates. RESULTS: 71 eyes of 71 patients were included. The overall CIM isolation rate was 81.7% (58 positive samples from 71 participants). 69 (81.2%) of isolates were Gram-positive cocci. Coagulase-negative Staphylococcus 31.8% and Streptococcus species 14.1% were the most isolated bacteria. Seven (9.9%) participants were positive for HSV-1. Fungi and Acanthamoeba were not detected. Moxifloxacin and chloramphenicol offered the best coverage for both Gram-positive and Gram-negative isolates when susceptibility was determined using known antimicrobial first quartile concentrations and European Committee on Antimicrobial Susceptibility Testing breakpoints, respectively. WGS identified known virulence genes associated with S. aureus keratitis. CONCLUSIONS: In a resource-poor setting, a CIM can be used to safely sample the cornea in patients presenting with suspected MK, enabling identification of causative microorganisms by culture and PCR. Although the microbiological spectrum found was limited to the dry season, these preliminary results could be used to guide empirical treatment.

Prediction of invasive candidal infection in critically ill patients with severe acute pancreatitis.

INTRODUCTION: Patients with severe acute pancreatitis are at risk of candidal infections carrying the potential risk of an increase in mortality. Since early diagnosis is problematic, several clinical risk scores have been developed to identify patients at risk. Such patients may benefit from prophylactic antifungal therapy while those patients who have a low risk of infection may not benefit and may be harmed. The aim of this study was to assess the validity and discrimination of existing risk scores for invasive candidal infections in patients with severe acute pancreatitis. METHODS: Patients admitted with severe acute pancreatitis to the intensive care unit were analysed. Outcomes and risk factors of admissions with and without candidal infection were compared. Accuracy and discrimination of three existing risk scores for the development of invasive candidal infection (Candida score, Candida Colonisation Index Score and the Invasive Candidiasis Score) were assessed. RESULTS: A total of 101 patients were identified from 2003 to 2011 and 18 (17.8%) of these developed candidal infection. Thirty patients died, giving an overall hospital mortality of 29.7%. Hospital mortality was significantly higher in patients with candidal infection (55.6% compared to 24.1%, P=0.02). Candida colonisation was associated with subsequent candidal infection on multivariate analysis. The Candida Colonisation Index Score was the most accurate test, with specificity of 0.79 (95% confidence interval [CI] 0.68 to 0.88), sensitivity of 0.67 (95% CI 0.41 to 0.87), negative predictive value of 0.91 (95% CI 0.82 to 0.97) and a positive likelihood ratio of 3.2 (95% CI 1.9 to 5.5). The Candida Colonisation Index Score showed the best discrimination with area under the receiver operating characteristic curve of 0.79 (95% CI 0.69 to 0.87). CONCLUSIONS: In this study the Candida Colonisation Index Score was the most accurate and discriminative test at identifying which patients with severe acute pancreatitis are at risk of developing candidal infection. However its low sensitivity may limit its clinical usefulness.