Macrophage mitochondrial bioenergetics and tissue invasion are boosted by an Atossa-Porthos axis in Drosophila.

Cellular metabolism must adapt to changing demands to enable homeostasis. During immune responses or cancer metastasis, cells leading migration into challenging environments require an energy boost, but what controls this capacity is unclear. Here, we study a previously uncharacterized nuclear protein, Atossa (encoded by CG9005), which supports macrophage invasion into the germband of Drosophila by controlling cellular metabolism. First, nuclear Atossa increases mRNA levels of Porthos, a DEAD-box protein, and of two metabolic enzymes, lysine-α-ketoglutarate reductase (LKR/SDH) and NADPH glyoxylate reductase (GR/HPR), thus enhancing mitochondrial bioenergetics. Then Porthos supports ribosome assembly and thereby raises the translational efficiency of a subset of mRNAs, including those affecting mitochondrial functions, the electron transport chain, and metabolism. Mitochondrial respiration measurements, metabolomics, and live imaging indicate that Atossa and Porthos power up OxPhos and energy production to promote the forging of a path into tissues by leading macrophages. Since many crucial physiological responses require increases in mitochondrial energy output, this previously undescribed genetic program may modulate a wide range of cellular behaviors.

Msl3 promotes germline stem cell differentiation in female Drosophila.

Gamete formation from germline stem cells (GSCs) is essential for sexual reproduction. However, the regulation of GSC differentiation is incompletely understood. Set2, which deposits H3K36me3 modifications, is required for GSC differentiation during Drosophila oogenesis. We discovered that the H3K36me3 reader Male-specific lethal 3 (Msl3) and histone acetyltransferase complex Ada2a-containing (ATAC) cooperate with Set2 to regulate GSC differentiation in female Drosophila. Msl3, acting independently of the rest of the male-specific lethal complex, promotes transcription of genes, including a germline-enriched ribosomal protein S19 paralog RpS19b. RpS19b upregulation is required for translation of RNA-binding Fox protein 1 (Rbfox1), a known meiotic cell cycle entry factor. Thus, Msl3 regulates GSC differentiation by modulating translation of a key factor that promotes transition to an oocyte fate.

Outcomes of Chronically Anticoagulated Patients Undergoing Split-Thickness Skin Grafting for Diabetic Foot Ulcers.

OBJECTIVE: Split-thickness skin grafting (STSG) is commonly used for wound closure in diabetic foot ulcers (DFUs). In many cases, patients with diabetes present on long-term anticoagulation therapy. The complications associated with anticoagulants can be discouraging to surgeons considering STSG. The goal of this study was to evaluate STSG outcomes in the setting of chronic anticoagulation across a large, multicenter database. METHODS: The authors queried the TriNetX Network, which provides access to electronic medical records for more than 75 million patients, to search for patients with a history of DFUs treated with STSG. They divided those found into two groups: long-term anticoagulant use prior to grafting and no long-term anticoagulant use. After matching, the researchers evaluated outcomes following STSG after 1 month and 5 years. RESULTS: The authors identified 722 patients on chronic anticoagulation with DFUs who were treated with STSG; 446 of these patients were matched to 446 patients with no prior anticoagulation. One month following STSG, the anticoagulated group showed no significant increase in death, graft failure, or regrafting. At 5 years, there was no significant increase in mortality, graft failure, regrafting, or lower extremity amputation rates. CONCLUSIONS: Chronic anticoagulation therapy does not lead to increased short- or long-term postoperative complications such as graft failure, regrafting, or increased amputation rates following STSG for wound closure. Negative outcomes following STSG for DFUs in chronically anticoagulated individuals are minimal, and grafting should be performed without hesitation.

A Torn or Reconstructed Anterior Cruciate Ligament Does Not Adversely Affect Clinical Outcome Scores and the Incidence of Reoperation After Unrestricted Kinematically Aligned Total Knee Arthroplasty.

BACKGROUND: There are no reports as to whether the condition of the anterior cruciate ligament (ACL) adversely affects the 2 to 3 year function and reoperation risk of a kinematically aligned (KA) total knee arthroplasty (TKA) performed with posterior cruciate ligament (PCL) retention and an intermediate medial conforming (MC) insert. METHODS: A single surgeon's prospective database query identified 418 consecutive primary TKAs performed between January 2019 and December 2019. The surgeon recorded the ACL condition in the operative note. Patients filled out the Forgotten Joint Score (FJS), Oxford knee score (OKS), and Knee Injury and Osteoarthritis Outcome Scores for Joint Replacement at the final follow-up. There were 299 patients with an intact ACL, 99 with a torn ACL, and 20 with a reconstructed ACL. The mean follow-up was 31 months (range, 20 to 45). RESULTS: The median FJS, OKS, and Knee Injury and Osteoarthritis Outcome Score (KOOS) of the reconstructed/torn/intact KA TKAs were 90/79/67, 47/44/43, and 92/88/80 points, respectively. The median OKS and KOOS of the reconstructed ACL cohort were 4 and 11 points higher than in the intact ACL cohort (P = .003, .04). One patient who had a reconstructed ACL underwent manipulation under anesthesia (MUA) for stiffness. The 5 reoperations in the intact ACL cohort were for instability (n = 2), revision after failed MUA for stiffness (n = 2), and infection (n = 1). CONCLUSION: These results suggest that patients who have a torn and reconstructed ACL can expect high function and a low risk of reoperation comparable to patients who have an intact ACL when treated with unrestricted, caliper-verified KA, PCL retention, and an intermediate MC insert.

Female terminalia morphology and cladistic relations among Tok-Tok beetles (Tenebrionidae: Sepidiini).

Tok-tokkies are one of the most iconic lineages within Tenebrionidae. In addition to containing some of the largest darkling beetles, this tribe is recognized for its remarkable form of sexual communication known as substrate tapping. Nevertheless, the phylogenetic relationships within the group remain poorly understood. This study investigates the usefulness of female terminalia morphology for delimiting Sepidiini and reconstructing relationships among it. Data on the structure of the ovipositors, genital tubes and spicula ventrali have been generated for >200 species representing 28 Pimeliinae tribes. This dataset was used in a comparative analysis at the subfamilial level, which resulted in recognition of several unique features of tok-tokkie terminalia. Additionally, new features linking phenotypically challenging tribes also were recovered (Cryptochilini + Idisiini + Pimeliini). Secondly, 23 characters linked to the structure of female terminalia were defined for tok-tok beetles. Cladistic analysis demonstrates the nonmonophyletic nature of most of the recognized subtribes. The morphological dataset was analysed separately and in combination with available molecular data (CAD, Wg, cox1, cox2, 28S). All obtained topologies were largely congruent, supporting the following changes: Palpomodina Kaminski & Gearner subtr.n. is erected to accommodate the genera Namibomodes and Palpomodes; Argenticrinis and Bombocnodulus are transferred from Hypomelina to Molurina; 153 species and subspecies previously classified within Psammodes are distributed over three separate genera (Mariazofia Kaminski nom.n., Piesomera stat.r., Psammodes sens.n.). Psammodes sklodowskae Kaminski & Gearner sp.n. is described. Preliminary investigation of the ovipositor of Mariazofia basuto (Koch) comb.n. was carried out with the application of microcomputed tomography, illuminating the muscular system as a reliable reference point for recognizing homologous elements in highly modified ovipositors.

Oral Healthcare Implications of Dedicated Online Communities: A Computational Content Analysis of the r/Dentistry Subreddit.

The current study explores communication expressed by participants in a subreddit surrounding oral health care, moderated by dentists and dental hygienists. The corpus was analyzed through Leximancer, a computer-assisted program used for computational content analyses of large data sets. Users' personal disclosures about ongoing dental concerns, advice about others' self-care, and the role of interpersonal communication with and among health care providers emerged as dominant themes. The findings suggest that online communities may serve an important role that dentists are unable to fill in their limited interactions with individual patients. Such interaction spaces may therefore offer a fertile environment for future interventions to promote beneficial practices and achieve positive health-related outcomes.

Glove and instrument changing to prevent bacterial contamination in infected wound debridement and closure procedures: A prospective observational study.

Many surgeons use a single table of instruments for both excisional debridement and coverage/closure of infected wounds. This study investigates the effectiveness of a two-table set-up of sterile instruments, in addition to glove exchange, to reduce instrument cross-contamination during these procedures. This is a prospective, single-site, institutional review board-approved observational study of surgical debridements of infected wounds over a 17-month period. Two separate sterile surgical tables were used for each case: Table A for initial wound debridement (debridement set-up) and Table B for wound coverage/closure (clean set-up). Swabs of each table and its respective instruments were taken after debridement but prior to coverage/closure. The primary outcome of interest was bacterial growth at 48 hours. There were 72 surgical cases included in this study. Culture results of Table A demonstrated bacterial growth in 23 of 72 (32%) cases at 48 hours compared with 5of 72 (7%) from Table B (P = .001). These data suggest that there is significant bacterial contamination of surgical instruments used for debridement of infected wounds. Use of a two-table set-up reduced instrument cross-contamination by 78%, suggesting avoidable re-contamination of the wound.

Influence of physical variables on the transfer of Salmonella Typhimurium LT2 between potato (Solanum tuberosum) and stainless steel via static and dynamic contact.

Bacterial cross-contamination between foods and contact surfaces can increase food safety risk; however, these processes are not well described in terms of fundamental variables. The objective was to determine the effect of sliding speed (3.75, 5.00, or 7.75 mm/s), contact time (5 or 40 s), normal pressure (~1217 to 8869 Pa), and number of sequential contacts on bacterial transfer to/from potato samples and stainless steel surfaces. Potato samples (~11 g, 3 × 3 × 1 cm) were either pulled across a stainless steel plate inoculated with Salmonella Typhimurium LT2 (~6.23 Log CFU/cm2) (dynamic contact) or placed on the inoculated plate for multiple sequential contacts on uninoculated squares (static contact). Salmonella on the potato and steel plate then were quantified by plating on modified trypticase soy agar. Bacterial transfer increased with increasing sliding speed (P = 0.0098) in dynamic tests and with contact time (P < 0.0001) in static tests. Salmonella on the inoculated potatoes decreased (P < 0.0001) from ~6.5 to ~5.5 Log CFU after 18 sequential static contacts with stainless steel. Reporting transfer results based on fundamental variables will improve the overall impact of bacterial transfer research on equipment design, cleaning/sanitation strategies, and overall food safety.

Acute stress impairs children's sustained attention with increased vulnerability for children of mothers reporting higher parenting stress.

Despite evidence that acute stress impairs attention in adults, there has been minimal research in children. Here, the effects of acute stress on Go/No-go performance were examined in young children (M age = 5.41 years). Given the critical role of the parent-child relationship to children's self-regulatory development, the extent to which parenting stress predicts children's cognitive vulnerability to acute stress and autonomic reactivity was also investigated. A between-groups design (n = 58 stress, n = 26 control) was used with oversampling of the stressor-exposed children to examine individual differences. The Parenting Stress Index and subscales were employed as a measure of parenting stress. Acute stress impaired children's sustained attention, but not inhibitory control. Higher parenting stress was associated with vulnerability to attentional impairment. Parenting distress was also positively associated with sympathetic reactivity to acute stress, but neither sympathetic nor parasympathetic reactivity was associated with attentional impairment. A conceptual model of pathways through which repetitive acute stress may contribute to self-regulatory difficulties is presented, including the potential buffering role of caregivers.

Plantar Foot Ulcer Recurrence in Neuropathic Patients Undergoing Percutaneous Tendo-Achilles Lengthening.

Equinus contracture carries 3- and 4-fold associations with diabetes and plantar foot ulceration, respectively. Percutaneous tendo-Achilles lengthening is a useful method to alleviate peak plantar pressure resulting from equinus. We aimed to evaluate the effectiveness of percutaneous tendo-Achilles lengthening and estimate the relative longevity of the approach in reducing ulcer recurrence. The medical records of patients with equinus contracture who underwent percutaneous tendo-Achilles lengthening from 2010 to 2017 were reviewed. Included patients presented with plantar ulcers and a gastroc-soleus equinus of any angle <10° of ankle dorsiflexion with the affected knee extended and flexed. Patients who received concomitant tendon lengthening procedures (including anterior tibial tendon or flexor digitorum longus) were excluded. Outcome measures included time to wound healing, time to ulcer recurrence, and development of transfer lesion. Ninety-one patients underwent percutaneous tendo-Achilles lengthening with subsequent pedal ulceration without concomitant procedures. A total of 69 (75.8%) patients had a plantar forefoot ulcer, 7 (7.7%) had midfoot ulcers, 5 (5.5%) had hindfoot ulcers, and 3 (3.3%) had ulcers in multiple locations. Seven patients received prophylactic tendo-Achilles lengthening. At a mean follow-up of 31.6 months (±26), 66 (78.6%) wounds healed at a median 12.9 weeks. A total of 29 patients (43.9%) experienced ulcer recurrence at a mean of 12 months. Twelve patients (13%) experienced a transfer lesion at a mean of 16.6 months. Tendo-Achilles lengthening can be an effective adjunctive approach to achieve wound healing and reduce long-term ulcer recurrence in patients with equinus contracture and neuropathic plantar foot ulcers. A relengthening procedure may be needed within approximately 12 months from index surgery.

Long Term Outcomes of Split-Thickness Skin Grafting to the Plantar Foot.

The most common consequence of neuropathy is a diabetic foot ulcer, which usually occurs on the plantar surface of the foot. Split-thickness skin grafting (STSG) has been shown in numerous studies to be an effective treatment for rapid coverage of diabetic ulcers. The purpose of this study is to retrospectively examine the outcomes of STSG to the plantar foot and determine the durability of this treatment compared to non-plantar surface STSG. This is a retrospective, single-center, institutional review board approved, case-control study of all patients who received STSG to their lower extremity for chronic ulcers from November 2013 to February 2017. Patients with ulcers on the plantar surface were considered cases, and non-plantar surface ulcers were considered controls. There were 182 patients who received STSG to the lower extremity, 52 to the plantar surface foot and 130 to non-plantar surface locations. Healing at 30 days was not significantly different between plantar and nonplantar ulcers (19% versus 28%, p = .199) but did become significant at 60, 90, and 365 days (21% versus 45%, p = .003; 33% versus 49%, p = .043; 38% versus 64%, p = .002, respectively). However, time to full healing was not significantly different between plantar and nonplantar groups (18.2 ± 19.5 versus 17.4 ± 21.6 weeks, mean ± standard deviation, p = .84). Recurrence was low for both groups (17% versus 10%, respectively), and there was no significant difference between groups (p = .17). Patients with plantar surface ulcers can achieve a durable coverage/closure of their wounds with STSG. When combined with appropriate patient selection and postoperative offloading, acceptable recurrence rates can be achieved.

Microbubble-mediated delivery of human adenoviruses does not elicit innate and adaptive immunity response in an immunocompetent mouse model of prostate cancer.

BACKGROUND: Gene transfer to malignant sites using human adenoviruses (hAds) has been limited because of their immunogenic nature and host specificity. Murine cells often lack some of the receptors needed for hAds attachment, thus murine cells are generally non-permissive for human adenoviral infection and replication, which limits translational studies. METHODS: We have developed a gene transfer method that uses a combination of lipid-encapsulated perfluorocarbon microbubbles and ultrasound to protect and deliver hAds to a target tissue, bypassing the requirement of specific receptors. RESULTS: In an in vitro model, we showed that murine TRAMP-C2 and human DU145 prostate cancer cells display a comparable expression pattern of receptors involved in hAds adhesion and internalization. We also demonstrated that murine and human cells showed a dose-dependent increase in the percentage of cells transduced by hAd-GFP (green fluorescent protein) after 24 h and that GFP transgene was efficiently expressed at 48 and 72 h post-transduction. To assess if our image-guided delivery system could effectively protect the hAds from the immune system in vivo, we injected healthy immunocompetent mice (C57BL/6) or mice bearing a syngeneic prostate tumor (TRAMP-C2) with hAd-GFP/MB complexes. Notably, we did not observe activation of innate (TNF-α and IL-6 cytokines), or adaptive immune response (neutralizing antibodies, INF-γ+ CD8+ T cells). CONCLUSIONS: This study brings us a step closer to demonstrating the feasibility of murine cancer models to investigate the clinical translation of image guided site-specific adenoviral gene therapy mediated by ultrasound-targeted microbubble destruction.

Predicting Exercise With a Personality Facet: Planfulness and Goal Achievement.

Establishing reliable predictors of health behavior is a goal of health psychology. A relevant insight from personality psychology is that facets can predict specific behaviors better than broad traits do. We hypothesized that we could predict physical activity with a facet of conscientiousness related to goal pursuit-planfulness. We measured the relationship between Planfulness Scale scores and physical activity in 282 individuals over a total of 20 weeks, using a piecewise latent growth curve model. We additionally tested whether planfulness uniquely relates to activity when compared with related constructs. Finally, ratings of participants' written goals were correlated with these personality traits and physical activity. We found that planfulness was positively associated with average visits to a recreational center, that planfulness explained unique variance in activity, and that planfulness correlated with the descriptiveness of written goals. We conclude that the Planfulness Scale is a valid measurement uniquely suited to predicting goal achievement.

Use of hyperbaric oxygen therapy for tissue ischemia after breast reconstruction.

INTRODUCTION: Mastectomy skin flap necrosis represents a significant complication of breast reconstructive procedures and is reported to occur in 30%-52% of patients undergoing breast reconstruction. Early identification of ischemia and early initiation of hyperbaric oxygen (HBO2) therapy can mitigate the effects of ischemia and rescue otherwise non-viable breast flap tissue. METHODS: We retrospectively examined the outcomes of HBO2 therapy in eight breasts with compromised mastectomy skin flaps between September 2015 and January 2017. Indocyanine green angiography (ICGA) was used to assess perfusion intraoperatively and post-HBO2 administration. RESULTS: Seven patients were referred for HBO2 within 24 hours of mastectomy. One patient failed to improve despite starting hyperbaric treatment within 24 hours. All other patients manifested successful healing of their mastectomy skin flaps with acceptable cosmesis after 10 HBO2 treatments. The mean relative perfusion of the at-risk area was 13.8% (±3.7%) pre-HBO2 and 101.6% (±37.3%) post-HBO2. The average area at-risk pre-HBO2 was 17.1 cm2 and reduced to zero post-HBO2. Relative perfusion values after HBO2 were found to be 6.8 (±3.4) times greater than those measured prior to HBO2. CONCLUSIONS: A short course of HBO2 may be sufficient to successfully rescue at risk post-mastectomy breast flaps. ICGA is a useful adjunct for evaluating post-mastectomy breast flap perfusion before and after HBO2 therapy.

Peripheral Vascular Disease Diagnostic Related Outcomes in Diabetic Charcot Reconstruction.

Postreconstructive outcomes were compared in diabetic patients with Charcot neuroarthropathy (CN) who had peripheral arterial disease (PAD) diagnosed with angiography versus patients who were diagnosed clinically. A retrospective review was performed of patients with diabetic CN requiring reconstruction secondary to ulceration and/or acute infection. Of the 284 patients in the CN osseous reconstruction cohort, after accounting for exclusion criteria, 59 (20.8%) patients with PAD were included in the analyses. Forty (67.8%) of these 59 patients were diagnosed with PAD clinically and 19 (32.2%) were diagnosed with the use of angiography. Bivariate analysis was used to compare outcomes between those diagnosed with PAD via angiography versus those diagnosed clinically for the following postreconstruction outcomes: wound healing, delayed healing, surgical site infection, pin tract infection, osteomyelitis, dehiscence, transfer ulcer, new site of Charcot collapse, contralateral Charcot event, nonunion, major lower extremity amputation, and return to ambulation. Bivariate analysis found return to ambulation postreconstruction (p = .0054) to be the only statistically significant factor. There was a trend toward significance for major lower extremity amputation, with higher rates of amputation in the clinically diagnosed PAD arm. Return to ambulation indicates improved functional outcomes. The main goal of limb salvage should be focused on improving the patient's functional performance. With significantly faster rates of return to ambulation and a trend toward decreased rates of major amputation, angiography was found to be a better assessor of PAD than clinical evaluations.

Enhancement of Meditation Analgesia by Opioid Antagonist in Experienced Meditators.

OBJECTIVE: Studies have consistently shown that long-term meditation practice is associated with reduced pain, but the neural mechanisms by which long-term meditation practice reduces pain remain unclear. This study tested endogenous opioid involvement in meditation analgesia associated with long-term meditation practice. METHODS: Electrical pain was induced with randomized, double-blind, cross-over administration of the opioid antagonist naloxone (0.15-mg/kg bolus dose, then 0.2-mg/kg per hour infusion dose) with 32 healthy, experienced meditation practitioners and a standardized open monitoring meditation. RESULTS: Under saline, pain ratings were significantly lower during meditation (pain intensity: 6.41 ± 1.32; pain unpleasantness: 3.98 ± 2.17) than at baseline (pain intensity: 6.86 ±1.04, t(31) = 2.476, p = .019, Cohen's d = 0.46; pain unpleasantness: 4.96 ±1.75, t(31) = 3.746, p = .001, Cohen's d = 0.68), confirming the presence of meditation analgesia. Comparing saline and naloxone revealed significantly lower pain intensity (t(31) = 3.12, p = .004, d = 0.56), and pain unpleasantness (t(31) = 3.47, p = .002, d = 0.62), during meditation under naloxone (pain intensity: 5.53 ± 1.54; pain unpleasantness: 2.95 ± 1.88) than under saline (pain intensity: 6.41 ± 1.32; pain unpleasantness: 3.98 ± 2.17). Naloxone not only failed to eliminate meditation analgesia but also made meditation analgesia stronger. CONCLUSIONS: Long-term meditation practice does not rely on endogenous opioids to reduce pain. Naloxone's blockade of opioid receptors enhanced meditation analgesia; pain ratings during meditation were significantly lower under naloxone than under saline. Possible biological mechanisms by which naloxone-induced opioid receptor blockade enhances meditation analgesia are discussed.

Heterozygous genotype at codon 129 correlates with prolonged disease course in Heidenhain variant sporadic CJD: case report.

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapid and fatal neurodegenerative disease defined by misfolded prion proteins accumulating in the brain. A minority of cases initially present with posterior cortical atrophy (PCA) phenotype, also known as Heidenhain variant or visual variant CJD. This case provides further evidence of sCJD presenting as PCA. The case also provides evidence for early DWI changes and cortical atrophy over 30 months before neurologic decline and subsequent death. The prolonged disease course correlates with prion protein codon 129 heterozygosity and coexistence of multiple prion strains.

The Neuroscience of Goals and Behavior Change.

The ways that people set, pursue, and eventually succeed or fail in accomplishing their goals are central issues for consulting psychology. Goals and behavior change have long been the subject of empirical investigation in psychology, and have been adopted with enthusiasm by the cognitive and social neurosciences in the last few decades. Though relatively new, neuroscientific discoveries have substantially furthered the scientific understanding of goals and behavior change. This article reviews the emerging brain science on goals and behavior change, with particular emphasis on its relevance to consulting psychology. I begin by articulating a framework that parses behavior change into two dimensions, one motivational (the will) and the other cognitive (the way). A notable feature of complex behaviors is that they typically require both. Accordingly, I review neuroscience studies on cognitive factors, such as executive function, and motivational factors, such as reward learning and self-relevance, that contribute to goal attainment. Each section concludes with a summary of the practical lessons learned from neuroscience that are relevant to consulting psychology.

Putting the brakes on the brakes: negative emotion disrupts cognitive control network functioning and alters subsequent stopping ability.

The ability to inhibit unwanted responses is critical for effective control of behavior, and inhibition failures can have disastrous consequences in real-world situations. Here, we examined how prior exposure to negative emotional stimuli affects the response-stopping network. Participants performed the stop-signal task, which relies on inhibitory control processes, after they viewed blocks of either negatively emotional or neutral images. In Experiment 1, we found that neural activity was reduced following negative image viewing. When participants were required to inhibit responding after neutral image viewing, we observed activation consistent with previous studies using the stop-signal task. However, when participants were required to inhibit responding after negative image viewing, we observed reductions in the activation of ventrolateral prefrontal cortex, dorsolateral prefrontal cortex, medial frontal cortex, and parietal cortex. Furthermore, analysis of neural connectivity during stop-signal task blocks indicated that across participants, emotion-induced changes in behavioral performance were associated with changes in functional connectivity, such that greater behavioral impairment after negative image viewing was associated with greater weakening of connectivity. In Experiment 2, we collected behavioral data from a larger sample of participants and found that stopping performance was impaired after negative image viewing, as seen in longer stop-signal reaction times. The present results demonstrate that negative emotional events can prospectively disrupt the neural network supporting response inhibition.

Neurologic Complications of Commonly Used Drugs in the Hospital Setting.

This chapter reviews the neurologic complications of medications administered in the hospital setting, by class, introducing both common and less common side effects. Detail is devoted to the interaction between pain, analgesia, sedation, and their residual consequences. Antimicrobials are given in nearly every hospital setting, and we review their capacity to produce neurologic sequelae with special devotion to cefepime and the antiviral treatment of human immunodeficiency virus. The management of hemorrhagic stroke has become more complex with the introduction of novel oral anticoagulants, and we provide an update on what is known about reversal of the new oral anticoagulants. Both central and peripheral nervous system complications of immunosuppressants and chemotherapies are reviewed. Because diagnosis is generally based on clinical acumen, alone, neurotoxic syndromes resulting from psychotropic medications may be easily overlooked until severe dysautonomia develops. We include a practical approach to the diagnosis of serotonin syndrome and neuroleptic malignant syndrome.