Implementation of a One-Day Living Kidney Donor Assessment Clinic to Improve the Efficiency of the Living Kidney Donor Evaluation: Program Report.

Purpose of program: A key barrier to becoming a living kidney donor is an inefficient evaluation process, requiring more than 30 tests (eg, laboratory and diagnostic tests), questionnaires, and specialist consultations. Donor candidates make several trips to hospitals and clinics, and often spend months waiting for appointments and test results. The median evaluation time for a donor candidate in Ontario, Canada, is nearly 1 year. Longer wait times are associated with poorer outcomes for the kidney transplant recipient and higher health care costs. A shorter, more efficient donor evaluation process may help more patients with kidney failure receive a transplant, including a pre-emptive kidney transplant (ie, avoiding the need for dialysis). In this report, we describe the development of a quality improvement intervention to improve the efficiency, effectiveness, and patient-centeredness of the donor candidate evaluation process. We developed a One-Day Living Kidney Donor Assessment Clinic, a condensed clinic where interested donor candidates complete all testing and consultations within 1 day. Sources of information: The One-Day Living Kidney Donor Assessment Clinic was developed after performing a comprehensive review of the literature, receiving feedback from patients who have successfully donated, and meetings with transplant program leadership from St. Joseph's Healthcare Hamilton. A multistakeholder team was formed that included health care staff from nephrology, transplant surgery, radiology, cardiology, social work, nuclear medicine, and patients with the prior lived experience of kidney donation. In the planning stages, the team met regularly to determine the objectives of the clinic, criteria for participation, clinic schedule, patient flow, and clinic metrics. Methods: Donor candidates entered the One-Day Clinic if they completed initial laboratory testing and agreed to an expedited process. If additional testing was required, it was completed on a different day. Donor candidates were reviewed by the nephrologist, transplant surgeon, and donor coordinator approximately 2 weeks after the clinic for final approval. The team continues to meet regularly to review donor feedback, discuss challenges, and brainstorm solutions. Key findings: The One-Day Clinic was implemented in March 2019, and has now been running for 4 years, making iterative improvements through continuous patient and provider feedback. To date, we have evaluated more than 150 donor candidates in this clinic. Feedback from donors has been uniformly positive (98% of donors stated they were very satisfied with the clinic), with most noting that the clinic was efficient and minimally impacted work and family obligations. Hospital leadership, including the health care professionals from each participating department, continue to show support and collaborate to create a seamless experience for donor candidates attending the One-Day Clinic. Limitations: Clinic spots are limited, meaning some interested donor candidates may not be able to enter a One-Day Clinic the same month they come forward. Implications: This patient-centered quality improvement intervention is designed to improve the efficiency and experience of the living kidney donor evaluation, result in better outcomes for kidney transplant recipients, and potentially increase living donation. Our next step is to conduct a formal evaluation of the clinic, measuring qualitative feedback from health care professionals working in the clinic and donor candidates attending the clinic, and measuring key process and outcome measures in donor candidates who completed the one-day assessment compared with those who underwent the usual care assessment. This program evaluation will provide reliable, regionally relevant evidence that will inform transplant centers across the country as they consider incorporating a similar one-day assessment model.

Objectifs du programme: Devenir donneur de rein vivant est difficile, le principal obstacle étant le processus d'évaluation inefficace auquel les candidats doivent se soumettre. Ce processus comporte plus de 30 examens (p. ex. tests de laboratoire et tests diagnostiques), questionnaires et consultations avec des spécialistes. Les candidats donneurs font plusieurs visites dans les hôpitaux et cliniques, et passent souvent plusieurs mois à attendre des rendez-vous et des résultats de tests. En Ontario (Canada), le délai médian pour l'évaluation d'un candidat au don est de près d'un an. Les temps d'attente plus longs sont associés à de moins bons résultats pour les receveurs d'une greffe rénale, ainsi qu'à des coûts de soins de santé plus élevés. Un processus d'évaluation plus court et plus efficace des donneurs potentiels permettrait à un plus grand nombre de patients atteints d'insuffisance rénale de recevoir une greffe, y compris une greffe préventive (c.-à-d. permettant d'éviter la dialyse). Cet article décrit une intervention d'amélioration de la qualité visant à augmenter l'efficience, l'efficacité et la personnalisation du processus d'évaluation des candidats au don. Nous avons développé une clinique d'un jour pour l'évaluation des donneurs de reins vivants (One-Day Living Kidney Donor Assessment Clinic), soit une clinique condensée où les candidats passent tous les tests et consultent un spécialiste dans la même journée. Sources de l'information: La clinique d'un jour pour l'évaluation des donneurs de reins vivants a été développée à la suite d'un examen approfondi de la littérature, de la consultation des commentaires de patients ayant donné avec succès et de rencontres avec les dirigeants du programme de transplantation du St Joseph's Healthcare d'Hamilton. Une équipe multipartite a été formée; celle-ci réunit du personnel soignant en néphrologie, chirurgie de transplantation, radiologie, cardiologie, travail social et médecine nucléaire, ainsi que des patients ayant une expérience vécue du don de rein. L'équipe s'est réunie régulièrement pendant les étapes de planification pour déterminer les objectifs, les paramètres et le calendrier de la clinique, ainsi que les critères de participation et le flux de patients. Méthodologie: Les donneurs potentiels qui avaient complété les tests de laboratoire initiaux et qui acceptaient de se soumettre à un processus accéléré ont été évalués à la clinique d'un jour. Si des tests supplémentaires étaient nécessaires, ceux-ci étaient effectués un autre jour. Les candidats ont été rencontrés par le néphrologue, le chirurgien de transplantation et le coordonnateur des dons environ deux semaines après leur visite à la clinique pour l'approbation finale. L'équipe multipartite continue de se réunir régulièrement pour examiner les commentaires des donneurs, discuter des défis et trouver des solutions. Principaux résultats: La clinique d'un jour, mise sur pied en mars 2019, est en activité depuis quatre ans et permet des améliorations itératives grâce à la rétroaction continue des patients et des soignants. À ce jour, plus de 150 candidats au don ont été évalués à la clinique. Les commentaires des donneurs sont quasi unanimement positifs (98 % des candidats ont déclaré être très satisfaits de la clinique), la plupart soulignant l'efficacité de la clinique et les conséquences minimes du processus sur les obligations professionnelles et familiales. La direction de l'hôpital, tout comme les professionnels de la santé des services participants, continue d'appuyer la clinique d'un jour et de collaborer à la création d'une expérience fluide pour les donneurs potentiels qui la fréquentent. Limites: Les places à la clinique sont limitées; ainsi, certains candidats au don d'un rein vivant pourraient ne pas pouvoir être admis dans le mois où ils se présentent à la clinique. Conclusion: Cette intervention d'amélioration de la qualité axée sur les patients est conçue pour augmenter l'efficacité du processus d'évaluation et bonifier l'expérience des donneurs de rein vivants. Elle vise également à améliorer les résultats des receveurs d'une greffe rénale et, potentiellement, augmenter le don vivant. La prochaine étape sera une évaluation formelle de la clinique, c'est-à-dire la mesure de la rétroaction qualitative des professionnels de la santé qui y travaillent et des candidats au don qui la fréquentent, et l'analyse des processus clés et des résultats des candidats évalués à la clinique d'un jour par rapport à ceux qui suivent le processus d'évaluation habituel. Cette évaluation du programme fournira des données probantes fiables et propres à la région qui pourront informer les centres de transplantation de tout le pays qui envisagent d'intégrer un processus d'évaluation similaire.

Impact of belantamab mafodotin-induced ocular toxicity on outcomes of patients with advanced multiple myeloma.

Belantamab mafodotin (BLMF) is a B-cell maturation antigen-directed antibody-drug conjugate, recently approved for advanced multiple myeloma (MM). The impact of BLMF-induced ocular toxicity on patient outcomes is unknown. We studied a cohort of 38 consecutively seen patients treated with BLMF outside of trials. Of those, 75% experienced ocular toxicity, with 69% developing keratopathy. Among patients requiring ocular toxicity-related permanent BLMF discontinuation (14%) or dose reduction (11%), 70% had progression of MM within a median of 3 months (95% confidence interval: 0.2-not reached) following BLMF interruption or dose reduction. Ocular toxicity is a major deterrent to the continuous use of BLMF in routine clinical practice. Measures to successfully prevent and mitigate ocular toxicity should be developed to achieve the full potential of this agent.

Novel Amylin Analogues Reduce Amyloid-ß Cross-Seeding Aggregation and Neurotoxicity.

BACKGROUND: Type 2 diabetes related human islet amyloid polypeptide (hIAPP) plays a dual role in Alzheimer's disease (AD). hIAPP has neuroprotective effects in AD mouse models whereas, high hIAPP concentrations can promote co-aggregation with amyloid-ß (Aß) to promote neurodegeneration. In fact, both low and high plasma hIAPP concentration has been associated with AD. Therefore, non-aggregating hIAPP analogues have garnered interest as a treatment for AD. The aromatic amino acids F23 and I26 in hIAPP have been identified as the key residues involved in self-aggregation and Aß cross-seeding. OBJECTIVE: Three novel IAPP analogues with single and double alanine mutations (A1 = F23, A2 = I26, and A3 = F23 + I26) were assessed for their ability to aggregate, modulate Aß oligomer formation, and alter neurotoxicity. METHODS: A range of biophysical methods including Thioflavin-T, gel electrophoresis, photo-crosslinking, circular dichroism combined with cell viability assays were utilized to assess protein aggregation and toxicity. RESULTS: All IAPP analogues showed significantly less self-aggregation than hIAPP. Co-aggregated Aß42-A2 and A3 also showed reduced aggregation compared to Aß42-hIAPP mixtures. Self- and co-oligomerized A1, A2, and A3 exhibited random coil conformations with reduced beta sheet content compared to hIAPP and Aß42-hIAPP aggregates. A1 was toxic at high concentrations compared to A2 and A3. However, co-aggregated Aß42-A1, A2, or A3 showed reduced neurotoxicity compared to Aß42, hIAPP, and Aß42-hIAPP aggregates. CONCLUSION: These findings confirm that hIAPP analogues with non-aromatic residues at positions 23 and 26 have reduced self-aggregation and the ability to neutralize Aß42 toxicity. This warrants further characterization of their protective effects in pre-clinical AD models.

Genome-Wide Analysis of Cadmium-Induced, Germline Mutations in a Long-Term Daphnia pulex Mutation-Accumulation Experiment.

BACKGROUND: Germline mutations provide the raw material for all evolutionary processes and contribute to the occurrence of spontaneous human diseases and disorders. Yet despite the daily interaction of humans and other organisms with an increasing number of chemicals that are potentially mutagenic, precise measurements of chemically induced changes to the genome-wide rate and spectrum of germline mutation are lacking. OBJECTIVES: A large-scale Daphnia pulex mutation-accumulation experiment was propagated in the presence and absence of an environmentally relevant cadmium concentration to quantify the influence of cadmium on germline mutation rates and spectra. RESULTS: Cadmium exposure dramatically changed the genome-wide rates and regional spectra of germline mutations. In comparison with those in control conditions, Daphnia exposed to cadmium had a higher overall A:T→G:C mutation rates and a lower overall C:G→G:C mutation rate. Daphnia exposed to cadmium had a higher intergenic mutation rate and a lower exonic mutation rate. The higher intergenic mutation rate under cadmium exposure was the result of an elevated intergenic A:T→G:C rate, whereas the lower exon mutation rate in cadmium was the result of a complete loss of exonic C:G→G:C mutations-mutations that are known to be enriched at 5-hydroxymethylcytosine. We experimentally show that cadmium exposure significantly reduced 5-hydroxymethylcytosine levels. DISCUSSION: These results provide evidence that cadmium changes regional mutation rates and can influence regional rates by interfering with an epigenetic process in the Daphnia pulex germline. We further suggest these observed cadmium-induced changes to the Daphnia germline mutation rate may be explained by cadmium's inhibition of zinc-containing domains. The cadmium-induced changes to germline mutation rates and spectra we report provide a comprehensive view of the mutagenic perils of cadmium and give insight into its potential impact on human population health. https://doi.org/10.1289/EHP8932.

Design and Characterization of a Cell-Penetrating Peptide Derived from the SOX2 Transcription Factor.

SOX2 is an oncogenic transcription factor overexpressed in nearly half of the basal-like triple-negative breast cancers associated with very poor outcomes. Targeting and inhibiting SOX2 is clinically relevant as high SOX2 mRNA levels are positively correlated with decreased overall survival and progression-free survival in patients affected with breast cancer. Given its key role as a master regulator of cell proliferation, SOX2 represents an important scaffold for the engineering of dominant-negative synthetic DNA-binding domains (DBDs) that act by blocking or interfering with the oncogenic activity of the endogenous transcription factor in cancer cells. We have synthesized an interference peptide (iPep) encompassing a truncated 24 amino acid long C-terminus of SOX2 containing a potential SOX-specific nuclear localization sequence, and the determinants of the binding of SOX2 to the DNA and to its transcription factor binding partners. We found that the resulting peptide (SOX2-iPep) possessed intrinsic cell penetration and promising nuclear localization into breast cancer cells, and decreased cellular proliferation of SOX2 overexpressing cell lines. The novel SOX2-iPep was found to exhibit a random coil conformation predominantly in solution. Molecular dynamics simulations were used to characterize the interactions of both the SOX2 transcription factor and the SOX2-iPep with FGF4-enhancer DNA in the presence of the POU domain of the partner transcription factor OCT4. Predictions of the free energy of binding revealed that the iPep largely retained the binding affinity for DNA of parental SOX2. This work will enable the future engineering of novel dominant interference peptides to transport different therapeutic cargo molecules such as anti-cancer drugs into cells.

Can quantifying morphology and TMEM119 expression distinguish between microglia and infiltrating macrophages after ischemic stroke and reperfusion in male and female mice?

BACKGROUND: Ischemic stroke is an acquired brain injury with gender-dependent outcomes. A persistent obstacle in understanding the sex-specific neuroinflammatory contributions to ischemic brain injury is distinguishing between resident microglia and infiltrating macrophages-both phagocytes-and determining cell population-specific contributions to injury evolution and recovery processes. Our purpose was to identify microglial and macrophage populations regulated by ischemic stroke using morphology analysis and the presence of microglia transmembrane protein 119 (TMEM119). Second, we examined sex and menopause differences in microglia/macrophage cell populations after an ischemic stroke. METHODS: Male and female, premenopausal and postmenopausal, mice underwent either 60 min of middle cerebral artery occlusion and 24 h of reperfusion or sham surgery. The accelerated ovarian failure model was used to model postmenopause. Brain tissue was collected to quantify the infarct area and for immunohistochemistry and western blot methods. Ionized calcium-binding adapter molecule, TMEM119, and confocal microscopy were used to analyze the microglia morphology and TMEM119 area in the ipsilateral brain regions. Western blot was used to quantify protein quantity. RESULTS: Post-stroke injury is increased in male and postmenopause female mice vs. premenopause female mice (p < 0.05) with differences primarily occurring in the caudal sections. After stroke, the microglia underwent a region, but not sex group, dependent transformation into less ramified cells (p < 0.0001). However, the number of phagocytic microglia was increased in distal ipsilateral regions of postmenopausal mice vs. the other sex groups (p < 0.05). The number of TMEM119-positive cells was decreased in proximity to the infarct (p < 0.0001) but without a sex group effect. Two key findings prevented distinguishing microglia from systemic macrophages. First, morphological data were not congruent with TMEM119 immunofluorescence data. Cells with severely decreased TMEM119 immunofluorescence were ramified, a distinguishing microglia characteristic. Second, whereas the TMEM119 immunofluorescence area decreased in proximity to the infarcted area, the TMEM119 protein quantity was unchanged in the ipsilateral hemisphere regions using western blot methods. CONCLUSIONS: Our findings suggest that TMEM119 is not a stable microglia marker in male and female mice in the context of ischemic stroke. Until TMEM119 function in the brain is elucidated, its use to distinguish between cell populations following brain injury with cell infiltration is cautioned.

Internet use behaviors, internet addiction and psychological distress among medical college students: A multi centre study from South India.

BACKGROUND: Internet Addiction (IA) among medical students and its association with psychological distress can impact their academic progress and long term career goals. IA would also indirectly impact community of health care professionals and the society. Thus, there is a need to investigate the IA among medical students. OBJECTIVES: This study was a first such attempt to explore internet use behavior's, IA, among a large group of medical students across multiple centers and its association with psychological distress primarily depression. METHODS & MATERIALS: 1763 medical students aged 18 to 21 years, pursuing Bachelor of Medicine; Bachelor of Surgery (MBBS) from three south Indian cities of Bangalore, Mangalore and Trissur participated in the study. The socio-educational and internet use behaviors data sheet was used to gather demographic information and patterns of internet use, IA Test (IAT) was utilized to assess IA and Self-Report Questionnaire (SRQ-20) assessed psychological distress primarily depression. RESULTS: Among the total N = 1763, 27% of medical students met criterion for mild addictive internet use, 10.4% for moderate addictive internet use, and 0.8% for severe addiction to internet. IA was higher among medical students who were male, staying in rented accommodations, accessed internet several times a day, spent more than 3 h per day on internet and had psychological distress. Age, gender, duration of use, time spent per day, frequency of internet use and psychological distress (depression) predicted IA. CONCLUSIONS: A substantial proportion of medical students have IA which can be detrimental for their medical education progress and long term career goals. Early identification and management of IA and psychological distress among medical students is crucial.

Biological Mechanisms of Cancer-Induced Depression.

Patients with cancer are more likely to develop depression than the general population, which negatively impacts their quality of life and prognosis. In order to identify effective antidepressants catered toward cancer patients, the biology of depression in the context of cancer must be well-understood. Many theories have emerged postulating the mechanisms underlying the development of depressive disorder. Here, we review the role inflammation, a hyperactive hypothalamic-pituitary-adrenal (HPA) axis, and glutamate excitotoxicity may play in cancer-induced depression. Hopefully, novel therapeutics targeting these dysregulated pathways may be potent in ameliorating depressive symptoms in the cancer population.

Necrotizing Sweet Syndrome of the Upper Extremity After Elective Hand Surgery.

Sweet syndrome, or acute febrile neutrophilic dermatosis, is a systemic disease process mainly characterized by hyperpyrexia and skin lesions. A newly described entity, necrotizing Sweet syndrome, is a severe and locally aggressive dermatological condition that clinically and histopathologically resembles a necrotizing soft tissue infection. It is characterized by pathergy, a nonspecific inflammatory response to cutaneous trauma resulting in a propagation of the disease. In contrast to a necrotizing infection, this condition responds to systemic steroids. A high clinical suspicion is required in order to distinguish a necrotizing polymicrobial infection from noninfectious necrotizing Sweet syndrome. We present a case following elective hand surgery.

Unrelated donor choices for allogeneic hematopoietic cell transplantation in Canada: an evaluation of factors influencing donor selection.

BACKGROUND: Utilization of unrelated donors and cord blood units (CBUs) for allogeneic hematopoietic cell transplantation continues to increase. Understanding the practices of donor selection by transplant centers is critical for unrelated donor registries and cord blood banks to optimize registry composition and inventory to meet patient need. STUDY DESIGN AND METHODS: Unrelated donor and CBU selection practices of Canadian transplant centers served by Canadian Blood Services' OneMatch Stem Cell & Marrow Network (OM) were reviewed, including HLA match level, locus of disparity, age, sex, and product choice (donor vs. CBU). RESULTS: HLA-matched donors within OM and/or international (INT) registries were preferentially investigated, underscoring the primary importance of HLA matching. In the case of HLA-mismatched donors, HLA-A disparities were most common while DRB1 mismatches were least common. Advanced age, sex, and lack of donor availability were the most frequent reasons that high-probability OM donors were overlooked in favor of INT donors. High-probability 10 of 10 HLA-matched female donors from OM were often avoided in favor of INT male donors. Use of female donors, however, increased in cases restricted to more HLA-disparate donor options. Caucasian patients were more likely to find 10 of 10 matched donors, whereas use of mismatched donors and CBUs were more prevalent among non-Caucasian patients. CONCLUSIONS: Recruitment and retention of young, male donors from diverse ethnic backgrounds may increase the usage of histocompatible OM donors for patients in need.

Risk of Exposure to Zika Virus and Impact on Cord Blood Banking and Adult Unrelated Donors in Hematopoietic Cell Transplantation: The Canadian Blood Services Experience.

Zika virus has emerged as a potential threat to the Canadian blood supply system. Stem cell donors within Canadian Blood Services' Cord Blood Bank (CBB) and OneMatch Stem Cell and Marrow Network (OM) now undergo screening measures designed to reduce the risk of Zika virus transmission. The impact these screening measures have on cord blood and unrelated adult stem cell donations is currently unknown. Among 146 donor workups initiated by OM between July 2016 and May 2017, 102 were completed and 44 workups were canceled. There were 17 potential donors (11.6%) with a risk of Zika virus exposure identified by the donor questionnaire (13 completed, 4 canceled workups). None of the workups involved a donor diagnosed with confirmed Zika virus within the past 6 months. Only 1 of the 44 canceled workups (and only 1 of 4 cases with a risk of Zika transmission) was canceled because of the risk of Zika transmission, and a backup donor was selected. Canadian Blood Services' CBB identified 25 of 875 cord blood units (2.9%) from women who donated their infants' cord blood and underwent screening that otherwise met the initial cell number thresholds for banking and had at least 1 risk factor for exposure to Zika virus. No women were diagnosed with Zika virus at any point of their pregnancy. All 25 units were discarded. Unrelated donors at OM have a higher incidence of a risk of exposure to Zika virus compared with cord blood donors. Only rarely did transplant centers cancel donor workups due to potential Zika virus exposure. The impact of screening for Zika virus exposure risk on cord blood banking was minor. Continued vigilance and surveillance is recommended.

Cryopreservation of adult unrelated donor products in hematopoietic cell transplantation: the OneMatch experience and systematic review of the literature.

BACKGROUND: The frequency of cryopreserving blood stem or progenitor products from unrelated donors is not known and the underlying reasons are poorly documented. Greater insight is needed to develop policies on cryopreservation that balance donor safety with patient needs. STUDY DESIGN AND METHODS: Cryopreservation requests between January 1, 2014, and May 31, 2016, at the OneMatch Stem Cell and Marrow Network at Canadian Blood Services were reviewed and a systematic review of the literature was performed. RESULTS: Thirty products of 719 (4.2%) unrelated donor collections facilitated by OneMatch were cryopreserved. Patient-related reasons were most common and included the need to delay transplant for continued antimicrobial treatment (six patients), patient too deconditioned to proceed with scheduled transplant (five patients), and/or need for more treatment for relapsed disease (three patients). Donor-related issues leading to cryopreservation requests were less common (five cases), mainly due to lack of donor availability after attempting to reschedule. Cryopreservation of a product that was never infused occurred infrequently (two cases, 7%). In our systematic review of the literature, 993 cases were identified in 32 published reports. Both patient-related and donor-related reasons were cited but not specifically reported, precluding quantitative insight regarding the relative frequency of causes. The impact of cryopreservation on hematopoietic engraftment appears negligible when compared to controls in a subset of studies; however, reporting of outcomes was inconsistent. CONCLUSION: Future studies with standard outcome measures are needed to clarify the impact of cryopreservation on engraftment and other transplant outcomes. International guidelines that consider the ethical framework surrounding requests for donor product cryopreservation are needed.

Behavioural Effects of Using Sulfasalazine to Inhibit Glutamate Released by Cancer Cells: A Novel target for Cancer-Induced Depression.

Despite the lack of robust evidence of effectiveness, current treatment options for cancer-induced depression (CID) are limited to those developed for non-cancer related depression. Here, anhedonia-like and coping behaviours were assessed in female BALB/c mice inoculated with 4T1 mammary carcinoma cells. The behavioural effects of orally administered sulfasalazine (SSZ), a system xc- inhibitor, were compared with fluoxetine (FLX). FLX and SSZ prevented the development of anhedonia-like behaviour on the sucrose preference test (SPT) and passive coping behaviour on the forced swim test (FST). The SSZ metabolites 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP) exerted an effect on the SPT but not on the FST. Although 5-ASA is a known anti-inflammatory agent, neither treatment with SSZ nor 5-ASA/SP prevented tumour-induced increases in serum levels of interleukin-1ß (IL-1ß) and IL-6, which are indicated in depressive disorders. Thus, the observed antidepressant-like effect of SSZ may primarily be attributable to the intact form of the drug, which inhibits system xc-. This study represents the first attempt at targeting cancer cells as a therapeutic strategy for CID, rather than targeting downstream effects of tumour burden on the central nervous system. In doing so, we have also begun to characterize the molecular pathways of CID.

The impact of sex on brain responses to smoking cues: a perfusion fMRI study.

BACKGROUND: Anecdotal and clinical theories purport that females are more responsive to smoking cues, yet few objective, neurophysiological examinations of these theories have been conducted. The current study examines the impact of sex on brain responses to smoking cues. METHODS: Fifty-one (31 males) cigarette-dependent sated smokers underwent pseudo-continuous arterial spin-labeled perfusion functional magnetic resonance imaging during exposure to visual smoking cues and non-smoking cues. Brain responses to smoking cues relative to non-smoking cues were examined within males and females separately and then compared between males and females. Cigarettes smoked per day was included in analyses as a covariate. RESULTS: Both males and females showed increased responses to smoking cues compared to non-smoking cues with males exhibiting increased medial orbitofrontal cortex and ventral striatum/ventral pallidum responses, and females showing increased medial orbitofrontal cortex responses. Direct comparisons between male and female brain responses revealed that males showed greater bilateral hippocampal/amygdala activation to smoking cues relative to non-smoking cues. CONCLUSIONS: Males and females exhibit similar responses to smoking cues relative to non-smoking cues in a priori reward-related regions; however, direct comparisons between sexes indicate that smoking cues evoke greater bilateral hippocampal/amygdalar activation among males. Given the current literature on sex differences in smoking cue neural activity is sparse and incomplete, these results contribute to our knowledge of the neurobiological underpinnings of drug cue reactivity.

Survival rates of mares and foals and postoperative complications and fertility of mares after cesarean section: 95 cases (1986-2000).

OBJECTIVE: To assess survival-to-discharge rates of mares and foals and postoperative complications and fertility in mares following cesarean section (C-section). DESIGN: Retrospective case series. ANIMALS: 95 mares. PROCEDURES: Medical and breeding records of mares that underwent C-section were reviewed; signalment, surgical technique, complications, survival-to-discharge rate, and pregnancy and foaling rates were recorded and evaluated. Foaling rates in the 3 years after C-section were compared with the cumulative foaling rate before C-section. RESULTS: C-section was performed because of dystocia (n = 71) or concurrent maternal disease (20) or was elective (4). Overall survival-to-discharge rate was 84% (80/95) for mares and 35% (28/80) for foals. Six of 15 mares that had partial fetotomies prior to C-section did not survive. Mares that had dystocia for < 90 minutes had the fewest complications. Cumulative foaling rate before C-section was 77% (394/509). Overall foaling rate for the 3 years after C-section was 52% (30/58) and 68% (13/19) when duration of dystocia was ≥ 90 minutes and < 90 minutes, respectively, and was 31 % (9/29) for mares ≥ 16 years old. Foaling rate was significantly lower for mares bred in the same year as C-section than for mares bred in later years. CONCLUSIONS AND CLINICAL RELEVANCE: Breeding in the same year as C-section, dystocia for ≥ 90 minutes before C-section, and mare age ≥ 16 years were associated with poor foaling rates. Prognosis for delivery of a live foal in years following C-section was good if duration of dystocia was < 90 minutes and the mare was < 16 years old at the time of surgery.

Peripheral sympathectomy as a novel treatment option for distal digital necrosis following parenteral administration of promethazine.

Promethazine is a commonly used medication to treat nausea and motion sickness. Case reports have recently surfaced on the dangers of parenteral administration of promethazine. We present a case report of a presumed intravenous injection of promethazine into an antecubital intravenous line resulting in necrosis of the ring finger distal to the DIP joint and hypoperfusion of the digits. Peripheral sympathectomy was performed to improve nutritional flow and improve ischemic pain. However, although this novel treatment option was successful, ultimately the patient had an amputation of her ring finger at the level of her middle phalanx. Although no proven successful treatment exists, the updated treatment options following inadvertent intra-arterial or perivascular administration are presented. Given the limited success of current treatment options for intra-arterial or perivascular extravasation, the staggering medical malpractice awards in such cases, and the numerous therapeutic alternatives to promethazine, the medical community should question the safety and continued administration of promethazine by an intravenous route.

Agonistic encounters and brain activation in dominant and subordinate male greater long-tailed hamsters.

During an agonistic encounter test, dominant male greater long-tailed hamsters (Tscheskia triton) initiated attacks sooner and displayed higher levels of aggression and flank marking behavior than their subordinate counterparts. Accordingly, subordinate males exhibited more defensive behavior than dominant ones. Specific patterns of neuronal activation, measured by Fos-immunoreactive staining (Fos-ir), were found in the hamster brain following agonistic interactions. Increased Fos-ir was observed in the bed nucleus of the stria terminalis (BST), ventromedial hypothalamus (VMH), and medial (MeA) and anterior cortical (ACo) nuclei of the amygdala (AMYG) in both dominant and subordinate males. In contrast, dominant males had significantly higher Fos-ir densities in the medial preoptic area (MPOA) than subordinate males, whereas subordinate males expressed higher densities of Fos-ir in the anterior hypothalamus (AH) and central nucleus of the amygdala (CeA). Additionally, Fos-ir levels in the MPOA were significantly correlated with aggression and Fos-ir levels in the AH and CeA were correlated with defensive behavior. Together, our data indicate distinct patterns of neuronal activation associated with agonistic encounters in a behavior-specific manner in male greater long-tailed hamsters.