Risk of venous thromboembolism in pregnant patients with active malignancy: A systematic review and meta-analysis.

INTRODUCTION: Cancer currently occurs in about 1 in 1000 pregnancies. Both active malignancy and pregnancy are individual risk factors for venous thromboembolism (VTE). The purpose of this systematic review/meta-analysis was to evaluate the rate of VTE in pregnant patients with active malignancy compared with pregnant patients without malignancy. MATERIAL AND METHODS: Embase, Medline/PubMed, Cochrane Database, and clinicaltrial.gov were search by a trained librarian from inception until June 2021, and limited to English and French language human studies using keywords related to pregnancy, neoplasm, and thrombosis. This study was prospectively registered with PROSPERO (CRD42021245886). Title, abstract, and full-text review was performed using the Covidence data management system. Two authors reviewed the studies independently. Of the 3821 articles screened, seven cohort studies were included that reported VTE rate in patients with active malignancy in pregnancy. RESULTS: A total of 5928 individuals had active malignancy and pregnancy. Active malignancy in pregnancy significantly increased the odds of a VTE (odds ratio [OR] 6.8, 95% confidence interval [CI] 3.8-12.1). Specifically, patients with thyroid (OR 2.7, 95% CI 1.3-6.3), cervix (OR 6.6, 95% CI 2.4-18.0), or other gynecological (OR 10.6, 95% CI 4.4-25.8) cancers; Hodgkin's lymphoma (OR 8.7, 95% CI 3.3-23.4); or acute leukemia (OR 17.1, 95% CI 10.9-26.8) all had increased odds, whereas those with brain cancer (OR 6.1, 95% CI 0.4-98.2), breast cancer (OR 2.5, 95% CI 0.3-17.4), malignant melanoma (OR 5.5, 95% CI 0.3-88.1), or non-Hodgkin's lymphoma (OR 3.2, 95% CI 0.8-12.9) malignancies did not have statistically significant increased odds for VTE. No studies reported whether prophylactic anticoagulation was used during pregnancy in this population; nor did they report timing in pregnancy of the VTE. The absolute risk for VTE in those with active malignancy was 0.9% compared with 0.2% in those without active malignancy in pregnancy. CONCLUSIONS: Pregnancy with active malignancy confers a significant increased risk for VTE compared with pregnancy alone. Given this finding, prophylactic anticoagulation during pregnancy and postpartum could be considered in this patient population. Data are underpowered to make firm recommendations per cancer type.

An examination of individual differences in levels of processing.

The present study examined individual differences in levels of processing. Participants completed a cued recall task in which they made either rhyme or semantic judgements on pairs of items. Pupillary responses during encoding were recorded as a measure of the allocation of attentional effort and participants completed multiple measures of working and long-term memory. The results suggested levels of processing effect in both accuracy and pupillary responses with deeper levels of processing demonstrating higher accuracy and larger pupillary responses than shallower levels of processing. Most participants demonstrated levels of processing effect, but there was substantial variability in the size of the effect. Variation in levels of processing was positively related to individual differences in long-term memory and the magnitude of the pupillary levels of processing effect, but not working memory. These results suggest that some of the variation in levels of processing is likely due to individual differences in the allocation of attentional effort (particularly to items processed deeply) during encoding.

Predictive Value of Laryngeal Penetration to Aspiration in a Cohort of Pediatric Patients.

Videofluoroscopic swallow studies (VFSS) provide dynamic assessment of the phases of swallowing under fluoroscopic visualization and allow for identification of abnormalities in the process, such as laryngeal penetration and aspiration. While penetration and aspiration both reflect degrees of swallowing dysfunction, the predictive potential of penetration for subsequent aspiration is not fully elucidated in the pediatric population. As a result, management strategies for penetration vary widely. Some providers may interpret any depth or frequency of penetration as a proxy for aspiration and implement various therapeutic interventions (e.g., modification of liquid viscosity) to eliminate penetration episodes. Some may recommend enteral feeding given the presumed risk of aspiration with penetration, even when aspiration is not identified during the study. In contrast, other providers may advise continued oral feeding without modification even when some degree of laryngeal penetration is identified. We hypothesized that the depth of penetration is associated with the likelihood of aspiration. Identification of predictive factors for aspiration following laryngeal penetration events has significant implications for selection of appropriate interventions. We performed a retrospective cross-sectional analysis of a random sample of 97 patients who underwent VFSS in a single tertiary care center over a 6 month period. Demographic variables including primary diagnosis and comorbidities were analyzed. We examined the association between aspiration and degrees of laryngeal penetration (presence or absence, depth, frequency) across diagnostic categories. Infrequent and shallow penetration events of any type of viscosity were less likely to be associated with aspiration event(s) during the same clinical encounter regardless of diagnosis. In contrast, children with consistent deep penetration of thickened liquids invariably demonstrated aspiration during the same study. Our findings show that shallow, intermittent laryngeal penetration of any viscosity type on VFSS was not consistent with clinical aspiration. These results provide further evidence that penetration-aspiration is not a uniform clinical entity and that nuanced interpretation of videofluoroscopic swallowing findings is necessary to guide appropriate therapeutic interventions.

The effects of auditory cues and weighted pens on handwriting in individuals with Parkinson's disease.

BACKGROUND: Micrographia, or small handwriting, is a common symptom of Parkinson's disease (PD). Weighted pens have previously been recommended to improve handwriting, but there is limited research supporting their effectiveness. Additionally, previous research has demonstrated that music as an auditory cue can reduce variability in fine motor movements, but its effect on handwriting in people with PD remains unknown. PURPOSE: This study explored potential handwriting interventions for people with PD by evaluating the effectiveness of weighted pens and auditory cues on handwriting. STUDY DESIGN: This was a pilot cohort study. METHODS: Eight older adults with PD used a standard pen and a weighted pen to write continuous cursive "l"s on 1.5-cm-lined paper for a total of 10 seconds while listening to auditory cues in 4 conditions: control (silence), metronome, activating music, and relaxing music. Kinematic data were measured with sensors attached to the tip of each pen, and muscle activity was measured with electromyography sensors adhered to the extensor digitorum communis and first dorsal interosseous. RESULTS: When writing with the standard pen, peak-to-peak time was reduced in the metronome (control = 0.807 ± 0.121 seconds, metronome = 0.701 ± 0.100 seconds, p = 0.024) and activating (control = 0.807 ± 0.121 seconds, activating = 0.691 ± 0.113 seconds, p = 0.009) conditions compared to the control condition. Furthermore, the weighted pen increased the variability of distance between letter peaks (standard = 0.187 ± 0.010, weighted = 0.482 ± 0.065, p = 0.033) and the variability of time needed to complete each letter (standard = 0.176 ± 0.010, weighted = 0.187 ± 0.016, p = 0.042) compared to the standard pen. Finally, area under the curve of the extensor digitorum communis was reduced in the metronome (metronome = 66.03 ± 25.74 mV, control = 88.98 ± 30.40 mV, p = 0.034) and activating music (activating = 66.49 ± 26.02 mV, control = 88.98 ± 30.40 mV, p = 0.012) conditions compared to control when writing with the standard pen. CONCLUSIONS: These results suggest that weighted pens may not improve handwriting in novice users, but auditory cues appear beneficial. This can inform future directions in the research and clinical application of handwriting interventions for persons with PD.

Post-randomization Differences in Condomless Vaginal Sex Among Women Randomized to Intramuscular Depot Medroxyprogesterone Acetate Injections, a Copper Intrauterine Device or a Levonorgestrel Implant in the ECHO Trial.

The Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial found no substantial difference in HIV acquisition risk between women randomised to injectable intramuscular depot medroxyprogesterone acetate (DMPA-IM), copper intrauterine device (Cu-IUD) or the levonorgestrel (LNG) implant. We evaluated post-randomization sexual behavior using an objective marker of condomless vaginal sex in a subset of participants. We conducted a sub-study among 458 ECHO participants at three sites (Cape Town, Johannesburg, Kisumu) to evaluate the frequency of condomless vaginal sex, measured by prostate specific antigen (PSA) detection in vaginal swabs, collected at the month 6 and final visit and the concordance of self-reported condomless vaginal sex with PSA detection, by randomized arm. We compared PSA detection frequency and concordance of PSA and self-reported condomless vaginal sex, by randomized group using Cochran-Mantel-Haenszel tests and adjusted generalized logistic growth curve models. PSA was detected less frequently in the DMPA-IM (16%), compared to the Cu-IUD (21%) and LNG implant (24%) groups, although results were not statistically significant in the unadjusted model when accounting for pre-specified multiple-testing criteria. There were significant differences in PSA detection between the DMPA-IM and LNG-implant groups (odds ratio 0.61 (95% CI 0.40, 0.94) in the adjusted model. There was moderate discordance between self-reported condomless vaginal sex and detection of PSA that was similar across randomized groups. These data suggest that women randomized to Cu-IUD and LNG implant may have had condomless sex more frequently than women randomized to DMPA-IM. The discordance between detectable PSA and self-reported sexual behaviour has important implications for design of future HIV prevention studies.

The influence of working memory capacity and lapses of attention for variation in error monitoring.

In two experiments, individual differences in working memory capacity (WMC), lapses of attention, and error monitoring were examined. Participants completed multiple WMC tasks along with a version of the Stroop task. During the Stroop, pupil diameter was continuously monitored. In both experiments, error phasic pupillary responses were larger than phasic pupillary responses associated with correct incongruent and correct congruent trials. WMC and indicators of lapses of attention were correlated with error pupillary response, suggesting that high WMC and low lapse individuals had enhanced error monitoring abilities compared with low WMC and high lapse individuals. Furthermore, in Experiment 2 error awareness abilities were associated with WMC, lapses of attention, and the error phasic pupillary responses. Importantly, individual differences in the susceptibility to lapses of attention largely accounted for the relationship between WMC and error monitoring in both experiments. Collectively, these results suggest that WMC is related to error monitoring abilities, but this association is largely due to individual differences in the ability to consistently maintain task engagement and avoid lapses of attention.

Effort Mobilization and Lapses of Sustained Attention.

The current study examined whether effort mobilization would enhance sustained attention and reduce lapses of attention. Participants performed a sustained attention task and were randomly assigned to either an effort condition where they were instructed to "Try Hard" on a subset of trials or were assigned to a control condition with no "Try Hard" instructions. Pupillary responses were continuously recorded, and periodically during the task participants were presented with thought probes to determine whether they were on or off task. The results suggested within the effort condition there were no behavioral differences between Try Hard and "Standard" trials. Preparatory pupil responses were increased in Try Hard trials, but there were no differences for phasic pupillary responses to stimulus onset. In contrast, examining differences between the effort and control conditions suggested that participants who received the Try Hard instructions demonstrated faster overall performance, a reduction in very long reaction times, and reported fewer off-task thoughts compared with participants in the control condition. Participants in the effort condition also demonstrated a larger ramp-up in pupillary responses during the preparatory interval and a larger phasic response to stimulus onset compared with participants in the control condition. These results are consistent with attention allocation models suggesting that participants in the effort condition mobilized more attentional effort than participants in the control condition, resulting in enhanced sustained attention and a reduction in lapses of attention. These results also are consistent with recent theories, which suggest that the locus coeruleus norepinephrine system is associated with effort mobilization.

The Utility of a Novel Definition of Health Care Regions in the United States in the Era of COVID-19: A Validation of the Pittsburgh Atlas Using Pneumonia Admissions.

STUDY OBJECTIVE: The COVID-19 pandemic in the United States has underscored the need to understand health care in a regional context. However, there are multiple definitions of health care regions available for conducting geospatial analyses. In this study, we compare the novel Pittsburgh Atlas, which defined regions for emergency care, with the existing definitions of regions, counties, and the Dartmouth Atlas, with respect to nonemergent acute medical conditions using pneumonia admissions. METHODS: We identified patients hospitalized with a primary diagnosis of pneumonia or a primary admitting diagnosis of sepsis with a secondary diagnosis of pneumonia in the Agency for Healthcare Research and Quality's State Inpatient Databases. We calculated the percentage of region concordant care, the localization index, and market share for 3 definitions of health care regions (the Pittsburgh Atlas, Dartmouth Atlas, and counties). We used logistic regression identified predictors of region concordant care. RESULTS: We identified 1,582,287 patients who met the inclusion criteria. We found that the Pittsburgh Atlas and Dartmouth Atlas definitions of regions performed similarly with respect to both localization index (92.0 [interquartile range 87.9 to 95.7] versus 90.3 [interquartile range 81.4 to 94.5]) and market share (8.5 [interquartile range 5.1 to 13.6] versus 9.4 [interquartile range 6.7 to 14.1]). Both atlases outperformed the localization index (67.5 [interquartile range 49.9 to 83.9]) and market share (20.0% [interquartile range 11.4 to 31.4]) of the counties. Within a given referral region, the demographic factors, including age, sex, race/ethnicity, insurance status, and the level of severity, affected concordance rates between residential and hospital regions. CONCLUSION: Because the Pittsburgh Atlas also has the benefit of respecting state and county boundaries, the use of this definition may have improved policy applicability without sacrificing accuracy in defining health care regions for acute medical conditions.

Endothelial Pannexin 1 Channels Control Inflammation by Regulating Intracellular Calcium.

The proinflammatory cytokine IL-1ß is a significant risk factor in cardiovascular disease that can be targeted to reduce major cardiovascular events. IL-1ß expression and release are tightly controlled by changes in intracellular Ca2+ ([Ca2+]i), which has been associated with ATP release and purinergic signaling. Despite this, the mechanisms that regulate these changes have not been identified. The pannexin 1 (Panx1) channels have canonically been implicated in ATP release, especially during inflammation. We examined Panx1 in human umbilical vein endothelial cells following treatment with the proinflammatory cytokine TNF-α. Analysis by whole transcriptome sequencing and immunoblot identified a dramatic increase in Panx1 mRNA and protein expression that is regulated in an NF-κB-dependent manner. Furthermore, genetic inhibition of Panx1 reduced the expression and release of IL-1ß. We initially hypothesized that increased Panx1-mediated ATP release acted in a paracrine fashion to control cytokine expression. However, our data demonstrate that IL-1ß expression was not altered after direct ATP stimulation in human umbilical vein endothelial cells. Because Panx1 forms a large pore channel, we hypothesized it may permit Ca2+ diffusion into the cell to regulate IL-1ß. High-throughput flow cytometric analysis demonstrated that TNF-α treatments lead to elevated [Ca2+]i, corresponding with Panx1 membrane localization. Genetic or pharmacological inhibition of Panx1 reduced TNF-α-associated increases in [Ca2+]i, blocked phosphorylation of the NF-κB-p65 protein, and reduced IL-1ß transcription. Taken together, the data in our study provide the first evidence, to our knowledge, that [Ca2+]i regulation via the Panx1 channel induces a feed-forward effect on NF-κB to regulate IL-1ß synthesis and release in endothelium during inflammation.

Multi-site observational maternal and infant COVID-19 vaccine study (MOMI-vax): a study protocol.

BACKGROUND: Pregnant women were excluded from investigational trials of COVID-19 vaccines. Limited data are available to inform pregnant and postpartum women on their decisions to receive a COVID-19 vaccine. METHODS: The goal of this observational, prospective cohort study is to evaluate the immunogenicity and safety of various Emergency Use Authorization (EUA) or licensed COVID-19 vaccines administered to pregnant or lactating women and describe the transplacental antibody transfer and kinetics of antibodies in mothers and infants. The study is adaptive, allowing additional groups to be added as new vaccines or vaccine regimens are authorized. Up to 20 clinical research institutions in the United States (U.S.) will be included. Approximately 200 pregnant women and 65 postpartum women will be enrolled per EUA or licensed COVID-19 vaccine formulation in the U.S. This study will include pregnant and postpartum women of all ages with and without chronic medical conditions. Their infants will be enrolled and followed beginning at birth in the pregnant cohort and beginning at the earliest possible time point in the postpartum cohort. Blood samples will be collected for immunogenicity outcomes and pregnancy and birth outcomes assessed among women and infants. Primary analyses will be descriptive and done by vaccine type and/or platform. DISCUSSION: Given the long-standing and legitimate challenges of enrolling pregnant individuals into clinical trials early in the vaccine development pipeline, this study protocol describes our current study and provides a template to inform the collection of data for pregnant individuals receiving COVID-19 or other vaccines. TRIAL REGISTRATION: NCT05031468 .

Cost comparison between spinal versus general anesthesia for hip and knee arthroplasty: an incremental cost study.

PURPOSE: Wait list times for total joint arthroplasties have been growing, particularly in the aftermath of the COVID-19 pandemic. Increasing operating room (OR) efficiency by reducing OR time and associated costs while maintaining quality allows the greatest number of patients to receive care. METHODS: We used propensity score matching to compare parallel processing with spinal anesthesia in a block room vs general anesthesia in a retrospective cohort of adult patients undergoing primary total hip arthroplasty (THA) and total knee arthroplasty (TKA). We compared perioperative costs, hospital costs, OR time intervals, and complications between the groups with nonparametric tests using an intention-to-treat approach. RESULTS: After matching, we included 636 patients (315 TKA; 321 THA). Median [interquartile range (IQR)] perioperative costs were CAD 7,417 [6,521-8,109], and hospital costs were CAD 10,293 [9,344-11,304]. Perioperative costs were not significantly different between groups (pseudo-median difference [MD], CAD -47 (95% confidence interval [CI], -214 to -130; P = 0.60); nor were total hospital costs (MD, CAD -78; 95% CI, -340 to 178; P = 0.57). Anesthesia-controlled time and total intraoperative time were significantly shorter for spinal anesthesia (MD, 14.6 min; 95% CI, 13.4 to 15.9; P < 0.001; MD, 15.9; 95% CI, 11.0 to 20.9; P < 0.001, respectively). There were no significant differences in complications. CONCLUSION: Spinal anesthesia in the context of a dedicated block room reduced both anesthesia-controlled time and total OR time. This did not translate into a reduction in incremental cost in the spinal anesthesia group.

RéSUMé: OBJECTIF: Les temps d'attente pour les arthroplasties articulaires totales ont augmenté, en particulier à la suite de la pandémie de COVID-19. Une augmentation de l'efficacité de la salle d'opération (SOP) fondée sur une réduction du temps en salle d'opération et des coûts associés, tout en maintenant la qualité, permettrait à un plus grand nombre de patients de recevoir des soins. MéTHODE: Nous avons utilisé l'appariement par score de propension pour comparer en parallèle des traitements par rachianesthésie dans une salle de bloc vs par anesthésie générale dans une cohorte rétrospective de patients adultes bénéficiant d'une arthroplastie totale de la hanche (ATH) et d'une arthroplastie totale du genou (ATG) primaires. Nous avons comparé les coûts périopératoires, les coûts hospitaliers, les intervalles de temps en SOP et les complications entre les groupes avec des tests non paramétriques en utilisant une approche d'intention de traiter. RéSULTATS: Après appariement, nous avons inclus 636 patients (315 ATG; 321 ATH). Les coûts périopératoires médians [écart interquartile (ÉIQ)] étaient de 7417 $ CA [6521 ­ 8109] et les coûts hospitaliers de 10 293 $ CA [9344 ­ 11 304]. Les coûts périopératoires n'étaient pas significativement différents entre les groupes (différence pseudomédiane [DM], −47 $ CA (intervalle de confiance à 95 % [IC], −214 à −130; P = 0,60), pas plus que les coûts hospitaliers totaux (DM, −78 $ CA; IC 95 %, −340 à 178; P = 0,57). Le temps sous anesthésie et le temps peropératoire total étaient significativement plus courts pour la rachianesthésie (DM, 14,6 min; IC 95 %, 13,4 à 15,9; P < 0,001; DM, 15,9; IC 95 %, 11,0 à 20,9; P < 0,001, respectivement). Aucune différence significative n'a été observée dans les complications. CONCLUSION: La rachianesthésie dans un contexte de salle de bloc dédiée a réduit à la fois le temps sous anesthésie et le temps total de SOP. Cela ne s'est pas traduit par une réduction du coût différentiel dans le groupe recevant une rachianesthésie.

Vaccine Breakthrough Cases in South Dakota: Impact of SARS-CoV-2 Variants in a Rural State.

BACKGROUND: Emergence of the SARS-CoV-2 Delta variant raised concern for greater transmissibility and severity of illness compared to the Alpha variant. Our objective was to compare SARS-CoV-2 vaccine breakthrough cases in South Dakota during the time periods where the Alpha and Delta variants of SARS-CoV-2 predominated. METHODS: Data were obtained from the South Dakota Department of Health's electronic disease surveillance system and South Dakota's Health Information Exchange. SARS-CoV-2 cases were matched with the immunization system data to verify vaccination status of vaccine breakthrough cases (VBC). The Alpha variant time-period (ATP) was defined as April 15-May 10, 2021 and the Delta variant time-period (DTP) as July 18-31, 2021. Case rates, demographics, risk factors, symptomology, and outcomes were compared for VBC during these periods. RESULTS: A total of 155 VBC were reported during the ATP and 153 during the DTP. The rate of SARS-CoV-2 VBC was 1.88 times higher for the DTP than the ATP. VBC during the ATP were more likely to present with no symptoms and during the DTP were more likely to present with subjective fever, cough, headache, loss or altered smell/taste, congestion, or postnasal drip. The average hospital length of stay was 6 days for the ATP and 4 days for the DTP. A total of 5 deaths were reported during the ATP compared to 1 death during the DTP. The non-statistically significant relation of the ATP and the DTP for hospital length of stay and number of deaths indicated a similar severity of disease. CONCLUSIONS: In fully vaccinated South Dakotans, the SARS-CoV-2 Delta variant was shown to cause 1.88 times higher breakthrough cases but resulted in similar severity of illness compared to the Alpha variant.

Doxycycline Versus Azithromycin for the Treatment of Rectal Chlamydia in Men Who Have Sex With Men: A Randomized Controlled Trial.

BACKGROUND: Azithromycin and doxycycline are both recommended treatments for rectal Chlamydia trachomatis (CT) infection, but observational studies suggest that doxycycline may be more effective. METHODS: This randomized, double-blind, placebo-controlled trial compared azithromycin (single 1-g dose) versus doxycycline (100 mg twice daily for 7 days) for the treatment of rectal CT in men who have sex with men (MSM) in Seattle and Boston. Participants were enrolled after a diagnosis of rectal CT in clinical care and underwent repeated collection of rectal swabs for nucleic acid amplification testing (NAAT) at study enrollment and 2 weeks and 4 weeks postenrollment. The primary outcome was microbiologic cure (CT-negative NAAT) at 4 weeks. The complete case (CC) population included participants with a CT-positive NAAT at enrollment and a follow-up NAAT result; the intention-to-treat (ITT) population included all randomized participants. RESULTS: Among 177 participants enrolled, 135 (76%) met CC population criteria for the 4-week follow-up visit. Thirty-three participants (19%) were excluded because the CT NAAT repeated at enrollment was negative. Microbiologic cure was higher with doxycycline than azithromycin in both the CC population (100% [70 of 70] vs 74% [48 of 65]; absolute difference, 26%; 95% confidence interval [CI], 16-36%; P < .001) and the ITT population (91% [80 of 88] vs 71% [63 of 89]; absolute difference, 20%; 95% CI, 9-31%; P < .001). CONCLUSIONS: A 1-week course of doxycycline was significantly more effective than a single dose of azithromycin for the treatment of rectal CT in MSM. CLINICAL TRIALS REGISTRATION: NCT03608774.

Seasonal patterns of callose deposition and xylem embolism in five boreal deciduous tree species.

PREMISE: Phloem tissue allows for sugar transport along the entirety of a plant and, thus, is one of the most important anatomical structures related to growth. It is thought that the sugar-conducting sieve tube may overwinter and that its cells persist multiple seasons in deciduous trees. One possible overwintering strategy is to build up callose on phloem sieve plates to temporarily cease their function. We tested the hypothesis that five deciduous tree species produce callose on their sieve plates on a seasonal basis. METHODS: Young shoots of five deciduous tree species were sampled periodically between April 2019 and February 2020 in Edmonton, Alberta, Canada. After enzymatic digestion of cytoplasmic constituents, cross sections were imaged using scanning electron microscopy to observe and quantify the level of callose deposition at monthly intervals, and sieve plate pore size was measured. Using a conductivity apparatus, we measured xylem native embolism during these sampling periods. RESULTS: Contrary to past work on some of the same species, we found little evidence that sieve tubes overwinter by becoming occluded with callose. Instead, we found that most sieve plates remain open. Xylem embolism was minimal during the peak growing season, but increased over winter. CONCLUSIONS: Many species had been assumed to deposit callose on sieve plates over winter, though anatomical and phenological phloem data were sparse. Our data do not support this notion.

A Novel Approach to Limb Salvage: Healing Transmetatarsal Amputations without a Viable Plantar Flap.

BACKGROUND: The lack of a viable plantar flap in patients undergoing transmetatarsal amputation has been considered an indication for below-knee amputation (BKA). In an effort to reduce limb loss in this patient population, we sought to review our experience with transmetatarsal amputation salvage in patients with an open, guillotine transmetatarsal amputation. We hypothesized that performing a transmetatarsal amputation without a viable flap would extend time of independent ambulation and improve limb salvage. METHODS: This is a retrospective review of 27 consecutive patients who did not have a viable plantar flap and who underwent an open, guillotine transmetatarsal amputation. Patients presented with a nonviable plantar flap due to either extensive tissue loss on initial presentation, or secondary transmetatarsal amputation (TMA) flap necrosis. Patients initially underwent an open, guillotine TMA for control of infection and debridement of nonviable tissue. To achieve best results, during procedure, the metatarsals were resected to be as flush with soft tissue as possible. Once infection was resolved and all nonviable tissue debrided, negative pressure wound therapy (NPWT) was applied to the open wound. NPWT was continued until a base of granulation tissue covered the previously exposed bone. Wound closure was obtained by either the application of a split-thickness skin graft (STSG) or through continued NPWT allowing the wound to heal by secondary intention. RESULTS: Between January 2016 and December 2018, there were 27 open TMAs performed in 27 patients. Two patients did not granulate sufficiently and underwent BKA. Fourteen patients underwent STSG for closure, whereas 11 patients continued with NPWT. In the STSG group, 12 (86%) of the patients are healed, with a median time to complete healing of 75 days (range 28-330 days); the remaining 2 are ambulatory and undergoing continued wound care. In the 11 patients who did not receive STSG, 7 (64%) are healed with a median time to heal of 165 days. Of the remaining 4 patients in this group, 3 are ambulatory and still undergoing wound care, one was lost to follow-up. Overall, 19 patients (70%) have completely healed with a median time to heal of 82 days. CONCLUSIONS: Limb salvage in patients with a nonviable plantar flap for TMA is possible and should be a considered procedure. This technique has the potential to improve functional outcomes and limb salvage in patients who might otherwise undergo BKA.

Encoding dynamics in free recall: Examining attention allocation with pupillometry.

In four experiments pupillary responses were used to examine attention allocation and encoding dynamics in free recall. In Experiment 1, pupillary responses increased (and then decreased) across serial position suggesting that attention was increasingly allocated to items during learning until working memory was overloaded. In Experiment 2, manipulating presentation duration resulted in larger and more sustained pupillary responses with increased presentation duration, suggesting that participants were likely engaging in more elaborative and attention-demanding processes. In Experiment 3a, manipulating list-length resulted in decreased pupillary responses across serial position suggesting that participants were prioritizing early list items and less attention was allocated to later items. In Experiment 3b, when list-length was known, pupillary responses in the long-list length condition tended to decrease across serial position whereas pupillary responses in the short list-length condition tended to increase and decrease across serial positon. These results suggest that participants flexibly allocate attention to items during encoding depending on the nature of the task and the types of processes that are engaged in. These results further suggest the potential of utilizing pupillary responses to track attention allocation during learning.

Analysis of Gene Expression Changes in Plants Grown in Salty Soil in Response to Inoculation with Halophilic Bacteria.

Soil salinity is an increasing problem facing agriculture in many parts of the world. Climate change and irrigation practices have led to decreased yields of some farmland due to increased salt levels in the soil. Plants that have tolerance to salt are thus needed to feed the world's population. One approach addressing this problem is genetic engineering to introduce genes encoding salinity, but this approach has limitations. Another fairly new approach is the isolation and development of salt-tolerant (halophilic) plant-associated bacteria. These bacteria are used as inoculants to stimulate plant growth. Several reports are now available, demonstrating how the use of halophilic inoculants enhance plant growth in salty soil. However, the mechanisms for this growth stimulation are as yet not clear. Enhanced growth in response to bacterial inoculation is expected to be associated with changes in plant gene expression. In this review, we discuss the current literature and approaches for analyzing altered plant gene expression in response to inoculation with halophilic bacteria. Additionally, challenges and limitations to current approaches are analyzed. A further understanding of the molecular mechanisms involved in enhanced plant growth when inoculated with salt-tolerant bacteria will significantly improve agriculture in areas affected by saline soils.

Shigella sonnei Outbreak Investigation During a Municipal Water Crisis-Genesee and Saginaw Counties, Michigan, 2016.

Objectives. To investigate a shigellosis outbreak in Genesee County, Michigan (including the City of Flint), and Saginaw County, Michigan, in 2016 and address community concerns about the role of the Flint water system.Methods. We met frequently with community members to understand concerns and develop the investigation. We surveyed households affected by the outbreak, analyzed Shigella isolate data, examined the geospatial distribution of cases, and reviewed available water quality data.Results. We surveyed 83 households containing 158 cases; median age was 10 years. Index case-patients from 55 of 83 households (66%) reported contact with a person outside their household who wore diapers or who had diarrhea in the week before becoming ill; results were similar regardless of household drinking water source. Genomic diversity was not consistent with a point source. In Flint, no space-time clustering was identified, and average free chlorine residual values remained above recommended levels throughout the outbreak period.Conclusions. The outbreak was most likely caused by person-to-person contact and not by the Flint water system. Consistent community engagement was essential to the design and implementation of the investigation.

Magnetic resonance enterography for predicting the clinical course of Crohn's disease strictures.

BACKGROUND AND AIMS: Strictures are the most common Crohn's disease complication, but their natural history is unknown. This study aimed to characterize inflammation, predict prognosis, and understand the impact of drug therapy using magnetic resonance enterography (MRE). METHODS: Patients with a stricture diagnosed on MRE over a 5-year period were reviewed for MRE disease extent and inflammation, clinical course, C-reactive protein, response to anti-TNF therapy, endoscopic dilatation, hospitalization, and surgery. RESULTS: 136 patients had 235 strictures (77, one and 59, ≥ 2 strictures). TREATMENT: 46% of patients underwent surgery after a median 6 months; median follow-up for those not requiring surgery was 41 months. Predictors of surgery: Hospitalization because of obstruction predicted subsequent surgery (OR 2.50; 95% CI 1.06-5.90) while anti-TNF therapy commenced at stricture diagnosis was associated with a reduced risk (OR 0.23; 95% CI 0.05-0.99). MRE characteristics associated with surgery were proximal bowel dilatation ≥ 30-mm diameter (OR 2.98; 95% CI 1.36-6.55), stricture bowel wall thickness ≥ 10-mm (OR 2.42; 95% CI 1.11-5.27), and stricture length > 5-cm (OR 2.56; 95% CI 1.21-5.43). 81% of patients with these three adverse MRE features required surgery versus 17% if none were present (P < 0.001). Accuracy for these three MRE variables predicting surgery was high (AUC 0.76). CONCLUSION: Magnetic resonance enterography findings in Crohn's disease strictures are highly predictive of the disease course and the need for future surgery. MRE may also identify who would benefit from treatment intensification. Anti-TNF therapy is associated with reduced risk of surgery and appears to alter the natural history of this complication.

E-cigarette Use Among Youth: Results from the 2019 South Dakota Youth Tobacco Survey.

BACKGROUND: The prevalence of e-cigarette use among youth is increasing in an alarming rate nationwide with over 5 million students currently using e-cigarettes in 2019. To better understand e-cigarette use in South Dakota, we examined the prevalence, access, reasons, and harm perception of e-cigarette among South Dakota youth. METHODS: We analyzed a representative sample of sixth to eighth grade students from the 2019 South Dakota Youth Tobacco Survey (YTS). Weighted estimates were computed to account for the complex sampling design and estimates were analyzed by geographic location and race/ethnicity. RESULTS: Among the 2,346 students, the prevalence of ever use of e-cigarettes among middle school students was 16.0 percent, a nearly 100 percent increase from 2017 YTS findings (8.2 percent). Approximately, seven percent (6.7 percent) reported use of an e-cigarette in the past 30 days, a nearly threefold increase from 2017 results (2.5 percent). Prevalence of current e-cigarette use was significantly higher among American Indian (12.7 percent) students and rural (8.3 percent) school students. The most common reported reasons for e-cigarette use was having friends/ family members that use them (49.6 percent) but also availability of flavors (18.6 percent). E-cigarette users obtained e-cigarettes predominantly through social sources (e.g., friends and peers). Nearly 30 percent (27.3 percent) reported not having enough information about e-cigarette's harm. CONCLUSIONS: In 2019, e-cigarettes were the most commonly used tobacco product among South Dakota middle school students. We found geographic and racial/ethnic disparity in e-cigarette use. Social influence and availability of flavors were important factors in promoting e-cigarette use. Continued efforts to implement population-level strategies to reduce e-cigarette use among youth are needed.