Perineuronal nets in the rat medial prefrontal cortex alter hippocampal-prefrontal oscillations and reshape cocaine self-administration memories.

The medial prefrontal cortex (mPFC) is a major contributor to relapse to cocaine in humans and to reinstatement in rodent models of cocaine use disorder. Output from the mPFC is potently modulated by parvalbumin (PV)-containing fast-spiking interneurons, the majority of which are surrounded by perineuronal nets (PNNs). We previously showed that ABC treatment with chondroitinase ABC (ABC) reduced the consolidation and reconsolidation of a cocaine conditioned place preference (CPP) memory. However, self-administration memories are more difficult to disrupt. Here we report in male rats that ABC treatment in the mPFC attenuated the consolidation and blocked the reconsolidation of a cocaine self-administration memory. However, reconsolidation was blocked when rats were given a novel, but not familiar, type of retrieval session. Further, ABC treatment prior to, but not after, memory retrieval blocked reconsolidation. This same treatment did not alter a sucrose memory, indicating specificity for cocaine-induced memory. In naive rats, ABC treatment in the mPFC altered levels of PV intensity and cell firing properties. In vivo recordings from the mPFC and dorsal hippocampus (dHIP) during the novel retrieval session revealed that ABC prevented reward-associated increases in high-frequency oscillations and synchrony of these oscillations between the dHIP and mPFC. Together, this is the first study to show that ABC treatment disrupts reconsolidation of the original memory when combined with a novel retrieval session that elicits coupling between the dHIP and mPFC. This coupling after ABC treatment may serve as a fundamental signature for how to disrupt reconsolidation of cocaine memories and reduce relapse.Significance Statement Powerful memories are associated with drug-taking behavior over extended periods, and these memories can drive relapse to drugs of abuse. The medial prefrontal cortex (mPFC) is a major contributor to relapse in cocaine use disorder. In a well-established rodent model of cocaine use disorder, we identify how removal of key extracellular matrix structures called perineuronal nets (PNNs) within the mPFC reduces the ability to update a cocaine memory. We further show that the ABC treatment within the mPFC impairs the coupling of oscillations between the mPFC and dorsal hippocampus during the updating of cocaine memory. This impaired communication between mPFC and hippocampal circuitry may act as a signature for disrupting cocaine-related memories to help break the cycle of relapse.

Improving the quality of medication administration practices in a tertiary Australian hospital: a best practice implementation project.

INTRODUCTION: Medication safety is an important health priority that focuses on preventing harm from medication-related events. Unsafe medication administration practices can lead to errors, which can cause avoidable injury (or harm) to patients. OBJECTIVES: This paper reports on an evidence implementation project conducted in a large tertiary hospital in Australia to improve nursing compliance with best practice recommendations for medication administration. METHODS: The project was guided by JBI's seven-phase approach to evidence implementation, using audit and feedback and a structured framework to identify barriers, enablers, and implementation strategies. RESULTS: The project resulted in improved compliance with best practice recommendations. This was achieved through multimodal strategies, including education, improved access to resources, and targeted feedback and discussion sessions to encourage culture and behavior change. CONCLUSIONS: The project improved nurses' medication administration practices, specifically in performing independent second checks. Collaborative efforts of the project leads facilitated the review of medication administration policy and the development of staff education resources. Patient engagement remains an area for improvement, along with the potential need for further ongoing medication education. SPANISH ABSTRACT: http://links.lww.com/IJEBH/A237.

Integrated oral care for patients with spinal cord injuries: perceptions of non-dental professionals.

PURPOSE: To understand the oral health attitudes, knowledge, and practices among non-dental professionals caring for patients with spinal cord injuries, as well as the barriers and facilitators to oral care across acute and rehabilitation hospital settings. MATERIALS AND METHODS: This study was a descriptive qualitative study. Nine focus groups with spinal cord injury clinicians from two Sydney hospitals were conducted (n = 35). A thematic analysis was undertaken. RESULTS: Four themes were constructed: understanding the impact of spinal cord injuries on oral health and wellbeing; limited support in the spinal cord injury unit to promote oral care; strategies that enable oral care promotion; and recommendations to expand scope in oral care and education. Although most clinicians considered oral health to be important there was a lack of guidelines to support standardised oral care practices. Barriers included lack of time, limited oral care resources, low priority and difficulty in accessing treatment. Staff were receptive to an integrated, multidisciplinary approach to oral care. CONCLUSION: This Australian first study provides insight into spinal cord injury clinicians' knowledge and practices of oral care. The findings will help guide future research in developing appropriate models of care to promote oral health among patients with spinal cord injuries.

Individuals with a spinal cord injury are at an increased risk of irregular oral hygiene practices and poor oral health compared to those without a spinal cord injuryProviding access to training and development of a model of care for oral health promotion to support non-dental health professionals working with individuals with a spinal cord injury can improve access to early intervention oral health careImplementing targeted training for staff, developing clear guidelines or protocols, and piloting an integrated multidisciplinary model of care could be potential future solutions to close this gap in care.

Perceptions of patients towards oral health care in a spinal cord injury rehabilitation unit: A qualitative study.

BACKGROUND: Individuals with spinal cord injuries (SCIs) are at an increased risk of poor oral health compared to the general population. However, little is known about the related barriers and facilitators experienced by these individuals within the hospital setting. OBJECTIVES: Understand the oral health knowledge, attitudes and practices of people with SCIs, barriers and facilitators to managing their oral health, and recommendations to improve oral care at acute/rehabilitation hospital settings. METHODS: Semi-structured interviews were conducted with 11 participants, from a major metropolitan hospital in Sydney, Australia. The interviews were thematically analysed. RESULTS: Three themes were constructed. Participants believed that the onus was on them to manage their oral health. Individuals also had limited knowledge of its importance to general health, and placed a lower priority on oral health compared to other aspects of health. All participants identified a combination of factors, such as cost, time, resources and prior negative experiences, that contributed to the neglect of their oral care. Participants also discussed the need of support from the multidisciplinary team and family/carers to facilitate oral care and identified various appropriate oral health education formats. CONCLUSION: This study highlighted some areas where oral health knowledge among people with SCIs could be improved. It also identified the need for oral health training for the multidisciplinary team, as well as carers, to better integrate oral care during rehabilitation in the hospital. The development of oral health interventions would need to utilise a co-design approach to best support clients and their carers to facilitate oral care self-management.

An environmental evaluation of urine-diverting dry toilets in Hiloweyn Camp, Dollo Ado, Ethiopia.

Safe and hygienic management of human waste is essential in humanitarian settings. Urine-diverting dry toilets (UDDTs) can enable this management in some humanitarian emergency settings. A seeded, longitudinal environmental study was conducted in Hiloweyn refugee camp, Dollo Ado, Ethiopia, to measure Escherichia coli and Ascaris suum ova inactivation within closed UDDT vaults and to document environmental conditions (temperature, moisture content, and pH) that could influence inactivation. Hiloweyn camp represented an optimal location for a desiccation-based sanitation technology such as the UDDT. E. coli and Ascaris ova inactivation was observed in UDDTs under warm, dry, alkaline conditions at 6, 9, and 12 months of storage; UDDTs with samples containing <1000 E. coli/g total solids increased from 30 % to 95 % over 12 months, and a >2.8-log10 reduction in Ascaris ova viability was observed after 6 months. Additional laboratory-based studies were conducted to provide insights into the field study findings and study the impact of hydrated lime on E. coli and Ascaris ova inactivation. Results suggest that adding hydrated lime to elevate pH > 12 may increase inactivation and decrease storage time. Overall, UDDTs could contribute to the safe and hygienic management of human waste in comparable warm and dry humanitarian settings.

Perineuronal nets in the rat medial prefrontal cortex alter hippocampal-prefrontal oscillations and reshape cocaine self-administration memories.

The medial prefrontal cortex (mPFC) is a major contributor to relapse to cocaine in humans and to reinstatement behavior in rodent models of cocaine use disorder. Output from the mPFC is modulated by parvalbumin (PV)-containing fast-spiking interneurons, the majority of which are surrounded by perineuronal nets (PNNs). Here we tested whether chondroitinase ABC (ABC)- mediated removal of PNNs prevented the acquisition or reconsolidation of a cocaine self-administration memory. ABC injections into the dorsal mPFC prior to training attenuated the acquisition of cocaine self-administration. Also, ABC given 3 days prior to but not 1 hr after memory reactivation blocked cue-induced reinstatement. However, reduced reinstatement was present only in rats given a novel reactivation contingency, suggesting that PNNs are required for the updating of a familiar memory. In naive rats, ABC injections into mPFC did not alter excitatory or inhibitory puncta on PV cells but reduced PV intensity. Whole-cell recordings revealed a greater inter-spike interval 1 hr after ABC, but not 3 days later. In vivo recordings from the mPFC and dorsal hippocampus (dHIP) during novel memory reactivation revealed that ABC in the mPFC prevented reward-associated increases in beta and gamma activity as well as phase-amplitude coupling between the dHIP and mPFC. Together, our findings show that PNN removal attenuates the acquisition of cocaine self-administration memories and disrupts reconsolidation of the original memory when combined with a novel reactivation session. Further, reduced dHIP/mPFC coupling after PNN removal may serve as a key biomarker for how to disrupt reconsolidation of cocaine memories and reduce relapse.

Assessment of Water, Sanitation, and Hygiene Conditions in Public Elementary Schools in Quetzaltenango, Guatemala, in the Context of the COVID-19 Pandemic.

Water, sanitation, and hygiene (WASH) services in schools are essential to reduce infectious disease transmission, including that of COVID-19. This study aimed to establish a baseline of WASH services in six public elementary schools in Guatemala, with a focus on hand hygiene. We used the WHO/UNICEF Joint Monitoring Programme (JMP) report indicators to assess the WASH infrastructure at each school. We collected water samples from easily accessible water points (pilas, or bathroom sinks) at each school to test for the presence of total coliforms and E. coli. In-depth interviews were carried out with teachers to understand hand hygiene practices and systems at school. Results indicate that all schools had water available at the time of the survey. All water samples at four schools tested positive for total coliforms and at one school, positive for E. coli. All schools had sanitation facilities, but services were limited. Only 43% of handwashing stations at schools had soap available. No school had disability-inclusive WASH services. Financial constraints and a lack of appropriate WASH infrastructure were the main barriers reported by teachers to meet hand hygiene needs at school. Appropriate access to WASH infrastructure and supplies could increase hand hygiene practices and improve learning conditions for students.

SARS-CoV-2 surface contamination in metro-Atlanta grocery stores.

While the COVID-19 pandemic has had a detrimental impact on many businesses worldwide, essential businesses, such as grocery stores, continued to operate despite potential disease transmission. Although the principal mode by which people are infected with SARS-CoV-2, the virus that causes COVID-19, is through exposure to respiratory droplets and very small particles carrying infectious virus, contaminated surfaces might play a role in transmission. We collected swab samples from frequently touched surfaces, including grocery carts, touchscreen monitors, credit card keypads, pharmacy counters, self-service food utensils, and refrigerator and freezer handles, in two metro-Atlanta grocery stores over the course of two sampling events in March 2021. Of the 260 swab samples collected, 6 (2.3%) samples were positive for SARS-CoV-2 RNA by reverse transcriptase quantitative polymerase chain reaction. Positive samples were collected from pharmacy (12.0% [3/25] samples), refrigerator/freezer aisles (2.5% [1/39] samples), and self-service food court (5.0% [2/40] samples) areas. Table/counter edge and underside surfaces represented 33% (2/6) of positive samples. These data suggest that risk of exposure to SARS-CoV-2 from frequently touched surfaces in grocery store settings is likely low; however, more frequent cleaning of surfaces in pharmacy and self-service food courts might be warranted.

A Case of Primary Amebic Meningoencephalitis Associated with Surfing at an Artificial Surf Venue: Environmental Investigation.

Naegleria fowleri is a thermophilic ameba found in freshwater that causes primary amebic meningoencephalitis (PAM) when it enters the nose and migrates to the brain. In September 2018, a 29-year-old man died of PAM after traveling to Texas. We conducted an epidemiologic and environmental investigation to identify the water exposure associated with this PAM case. The patient's most probable water exposure occurred while surfing in an artificial surf venue. The surf venue water was not filtered or recirculated; water disinfection and water quality testing were not documented. N. fowleri and thermophilic amebae were detected in recreational water and sediment samples throughout the facility. Codes and standards for treated recreational water venues open to the public could be developed to address these novel venues. Clinicians and public health officials should also consider novel recreational water venues as a potential exposure for this rare amebic infection.

Net gain and loss: influence of natural rewards and drugs of abuse on perineuronal nets.

Overindulgence, excessive consumption, and a pattern of compulsive use of natural rewards, such as certain foods or drugs of abuse, may result in the development of obesity or substance use disorder, respectively. Natural rewards and drugs of abuse can trigger similar changes in the neurobiological substrates that drive food- and drug-seeking behaviors. This review examines the impact natural rewards and drugs of abuse have on perineuronal nets (PNNs). PNNs are specialized extracellular matrix structures that ensheathe certain neurons during development over the critical period to provide synaptic stabilization and a protective microenvironment for the cells they surround. This review also analyzes how natural rewards and drugs of abuse impact the density and maturation of PNNs within reward-associated circuitry of the brain, which may contribute to maladaptive food- and drug-seeking behaviors. Finally, we evaluate the relatively few studies that have degraded PNNs to perturb reward-seeking behaviors. Taken together, this review sheds light on the complex way PNNs are regulated by natural rewards and drugs and highlights a need for future studies to delineate the molecular mechanisms that underlie the modification and maintenance of PNNs following exposure to rewarding stimuli.

Neural Mechanisms Mediating Sex Differences in Motivation for Reward: Cognitive Bias, Food, Gambling, and Drugs of Abuse.

Sex differences in motivation for food rewards, gambling, and drugs of abuse are modulated by multiple factors, including sensory stimuli, gonadal hormones, and cognitive bias. Cues, drugs of abuse, and a high-fat diet can significantly impact neural signaling in the reward system and functioning of neural systems that regulate executive functions differentially in males and females. Additionally, sex differences in risky decision-making, cognitive bias, and motivation for food and drugs of abuse are mediated by gonadal hormones in both sexes. As neuroscientists analyze data from both sexes, it is becoming apparent that these differences are not simply mediated by hormones in females, but involve sex differences in the specific neural responses to stimuli, including both external stimuli and internal hormonal signals. Understanding sex differences in the mechanisms underlying reward-seeking behaviors and the development of substance use disorders will help uncover potential therapies and treatments that will benefit both men and women. Based on these observations, it is essential that females are included in neuroscience research.

Dietary Fatty Acid Composition Impacts the Fatty Acid Profiles of Different Regions of the Bovine Brain.

Fatty acid composition across functional brain regions was determined in bovine brains collected from cattle that were provided supplements of calcium salts containing either palm or fish oil. The Angus cattle were divided into two groups, with one group offered the supplement of calcium salts of palm oil and the other offered the calcium salts of fish oil (n = 5 females and n = 5 males/supplement) for 220 days. These supplements to the basal forage diet were provided ad libitum as a suspension in dried molasses. The fish oil exclusively provided eicosapentaenoic acid (EPA, C20:5 n-3) and docosahexaenoic acid (DHA, C22:6 n-3). The functional regions were dissected from the entire brains following commercial harvest. While the cattle provided diets supplemented with the calcium salts of palm oil had increased (p < 0.01) liver concentrations of C18:1 n-9, C18:2 n-6, and arachidonic acid, the fish-oil-supplemented cattle had greater (p < 0.01) concentrations of liver EPA, DHA, and C18:3 n-3. In the brain, DHA was the most abundant polyunsaturated fatty acid. In the amygdala, pons, frontal lobe, internal capsule, and sensory cortex, DHA concentrations were greater (p < 0.05) in the brains of the cattle fed fish oil. Differences among the supplements were small, indicating that brain DHA content is resistant to dietary change. Arachidonic acid and C22:4 n-6 concentrations were greater across the regions for the palm-oil-supplemented cattle. EPA and C22:5 n-3 concentrations were low, but they were greater across the regions for the cattle fed fish oil. The effects of sex were inconsistent. The fatty acid profiles of the brain regions differed by diet, but they were similar to the contents reported for other species.

Impact of Perineuronal Net Removal in the Rat Medial Prefrontal Cortex on Parvalbumin Interneurons After Reinstatement of Cocaine Conditioned Place Preference.

Parvalbumin (PV)-positive cells are GABAergic fast-spiking interneurons that modulate the activity of pyramidal neurons in the medial prefrontal cortex (mPFC) and their output to brain areas associated with learning and memory. The majority of PV cells within the mPFC are surrounded by a specialized extracellular matrix structure called the perineuronal net (PNN). We have shown that removal of PNNs with the enzyme chondroitinase-ABC (Ch-ABC) in the mPFC prevents the consolidation and reconsolidation of cocaine-associated conditioned place preference (CPP) memories. Here we examined the extent to which retrieval of a CPP memory during cocaine-primed reinstatement altered the levels and function of PV neurons and their surrounding PNNs during the reconsolidation period. We further determined the extent to which PNN removal prior to reinstatement altered PV intensity levels and PV cell function. Male Sprague-Dawley rats were trained for cocaine-induced conditioned place preference (CPP) followed by extinction training, microinjection of Ch-ABC in the prelimbic PFC, and cocaine-induced reinstatement. Rats were sacrificed immediately prior to reinstatement or at 2 h, 6 h, or 48 h after reinstatement for immunohistochemistry or 2 h later for electrophysiology. Our findings indicate that PNN removal only partially diminished reinstatement. Cocaine-primed reinstatement produced only minor changes in PNN or PV intensity in vehicle controls. However, after PNN removal, the intensity of remaining PNN-surrounded PV cells was decreased at all times except at 2 h post-reinstatement, at which time cocaine increased PV intensity. Consistent with this, in vehicle controls, PV neurons naturally devoid of PNNs showed a similar pattern to Ch-ABC-treated rats prior to and after cocaine reinstatement, suggesting a protective effect of PNNs on cocaine-induced changes in PV intensity. Using whole-cell patch-clamp, cocaine-primed reinstatement in Ch-ABC-treated rats decreased the number of elicited action potentials but increased excitatory synaptic transmission, which may have been compensatory. These findings suggest that without PNNs, cocaine-induced reinstatement produces rapid changes in PV intensity and PV cell excitability, which may in turn regulate output of the mPFC post-memory retrieval and diminish the maintenance of cocaine memory during reconsolidation.

Outcomes After Injection-Based Therapy: A Pain Outcomes Questionnaire for Veterans Univariate Analysis.

Background: The Pain Outcomes Questionnaire-For Veterans (POQ-VA) was developed within the Veterans Health Administration (VHA) as a brief but psychometrically sound pain outcomes instrument that assesses key domains. In routine clinical practice, it is valid and reliable for evaluating effectiveness of treatment of chronic noncancer pain in veterans. We hypothesized that POQ-VA scores would improve across multiple domains in the veteran population following injection-based interventional treatment for chronic pain. Methods: We aggregated all available POQ-VA reports from veterans who underwent ≥ 1 interventional pain procedures between April 1, 2009 and April 1, 2019. Patients were included who had pre- and posttreatment POQ-VA results separated by ≤ 6 months (N = 112). A paired-samples t test was used to compare means, standard deviations, and ranges for each POQ-VA domain. Individual question responses were analyzed using a nonparametric Wilcoxon matched-pairs signed-rank test. Results: All POQ-VA domains showed a statistically significant decrease posttreatment (P ≤ .03). Directionally, the responses to 17 of 20 individual POQ-VA questions reflect a small but statistically significant positive treatment response (P < .04). Conclusions: Most veterans undergoing injection therapy for chronic pain had statistically significant improvements in POQ-VA measures within a 6-month period. To conduct more rigorous, multivariate studies, continued and widespread use of the POQ-VA instrument is warranted.

Role of cathepsin K in the expression of mechanical hypersensitivity following intra-plantar inflammation.

Persistent/chronic inflammatory pain involves multiple pathophysiological mechanisms and is far more complex than acute/momentary pain. Current therapeutics for chronic inflammatory pain are often not effective because the etiology responsible for the pain is not addressed by traditional pharmacological treatments. Cathepsin K is a cysteine protease that has mostly been studied in the context of bone and joint disorders. Previous work by others has shown that inhibition of cathepsin K activity reduces osteoarthritis-associated nociception in joints. However, the role of cathepsin K in cutaneous inflammation is understudied. We assessed the effectiveness of genetic deletion or pharmacological inhibition of cathepsin K in male mice on the expression of nocifensive behaviors after formalin injection or mechanical and thermal hypersensitivity after injection of complete Freund's adjuvant (CFA) into the mouse hind paw. Our data demonstrate that cathepsin K knockout mice (Ctsk-/-) have a reduction in nocifensive behaviors in the formalin test. In addition, Ctsk-/- do not develop mechanical hypersensitivity after CFA injection for up to 7 days. Moreover, we found that inhibition of cathepsin K reduced mechanical hypersensitivity after CFA injection and mRNA levels, protein levels, and cathepsin K activity levels were elevated after CFA injection. Based upon our data, cathepsin K is indicated to play a role in the expression of chemically-induced cutaneous hypersensitivity, as Ctsk-/- mice do not develop mechanical hypersensitivity and show a reduction in nocifensive behaviors. Further research is needed to determine whether attenuating cathepsin K activity may generate a clinically relevant therapeutic.

Acute high-intensity interval exercise attenuates incubation of craving for foods high in fat.

OBJECTIVE: Food-seeking behaviors can be driven by food-associated cues, and palatable food seeking in response to food cues is a risk factor for obesity development. Cue-induced food seeking increases following a period of abstinence, a behavioral phenomenon known as "incubation of craving," which may contribute to an individual's difficulty abstaining from palatable foods. Pharmacological and environmental manipulations have been employed to try and reduce incubation of craving, albeit primarily in drug abuse paradigms. The goal of this study was to determine whether forced exercise can attenuate incubation of high-fat food craving. METHODS: Male Sprague Dawley rats learned to self-administer high-fat pellets (60%) in combination with a compound cue (light + tone). The influence of high-intensity interval exercise on the time-dependent increase in cue-induced lever responding was investigated 30 days after the first cue test. RESULTS: Rats exposed to exercise during abstinence did not express incubation of craving. CONCLUSIONS: The results suggest that high-intensity exercise can prevent the establishment of incubation of craving for foods high in fat and may reduce cue-induced maladaptive food-seeking behaviors that contribute to overeating and obesity.

Acceptability of urine diversion dry toilets in Dollo Ado refugee camp, Ethiopia.

Given the increasing frequency and duration of humanitarian emergencies worldwide, there is a need to identify a greater range of effective and contextually appropriate water, sanitation and hygiene (WASH) interventions. Typical sanitation systems may be poorly suited for some of the conditions in which humanitarian emergencies can occur, such as in drought-prone regions. Urine-diversion dry toilets (UDDTs) are one potential alternative sanitation option which can be used in these conditions. Between 2014 and 2016, the U.S. Centers for Disease Control and Prevention (CDC) partnered with local agencies to evaluate the acceptability of UDDTs in a refugee camp in Ethiopia. The overall goals were to provide evidence regarding the level of adoption and satisfaction with UDDTs in this emergency context and the factors associated with satisfaction. Two cross-sectional surveys were conducted 18-months apart, using a stratified design to sample UDDT and latrine users for comparison. The proportion who reported to use their UDDT consistently was 88.8% (95% CI 85.1-92.5) in the first survey and 93.4% (95% CI 90.6-96.2) in the second survey. Reported satisfaction levels were significantly higher among respondents in the second survey (p < 0.0001), where 97.0% (95% CI 95.1-98.9) of respondents stated either that they were mostly or very satisfied with their UDDT. There was no significant difference detected in satisfaction between UDDT and latrine users (p = 0.28). Using a multivariable logistic regression model, we identified several factors associated with a higher level of satisfaction with UDDTs. Those who had previously (before coming to the camp) used a pit latrine (AOR = 4.2; 95% CI 1.4-12.7) or had no sanitation system (AOR = 2.4; 95% CI 1.3-4.4) relative to a pour-flush toilet, had a clean UDDT (AOR = 2.8; 95% CI 1.7-4.6), had been in the camp for a longer time period (AOR = 2.3; 95% CI 1.7-3.0), did not share their UDDT (AOR = 1.8; 95% CI 1.0-3.0) and had used their UDDT for a longer time period (AOR = 1.7; 95% CI 1.2-2.4) had higher odds of satisfaction. The findings demonstrate that UDDTs have been effectively introduced and utilized in this context and this may have implications for other humanitarian settings where they can be similarly managed.

Diurnal changes in perineuronal nets and parvalbumin neurons in the rat medial prefrontal cortex.

Perineuronal nets (PNNs) surrounding fast-spiking, parvalbumin (PV) interneurons provide excitatory:inhibitory balance, which is impaired in several disorders associated with altered diurnal rhythms, yet few studies have examined diurnal rhythms of PNNs or PV cells. We measured the intensity and number of PV cells and PNNs labeled with Wisteria floribunda agglutinin (WFA) and also the oxidative stress marker 8-oxo-deoxyguanosine (8-oxo-dG) in rat prelimbic medial prefrontal cortex (mPFC) at Zeitgeber times (ZT) ZT0 (lights-on, inactive phase), ZT6 (mid-inactive phase), ZT12 (lights-off, active phase), and ZT18 (mid-active phase). Relative to ZT0, the intensities of PNN and PV labeling were increased in the dark (active) phase compared with the light (inactive) phase. The intensity of 8-oxo-dG was decreased from ZT0 at all times (ZT6,12,18). We also measured GAD 65/67 and vGLUT1 puncta apposed to PV cells with and without PNNs. There were more excitatory puncta on PV cells with PNNs at ZT18 vs. ZT6, but no changes in PV cells without PNNs and no changes in inhibitory puncta. Whole-cell slice recordings in fast-spiking (PV) cells with PNNs showed an increased ratio of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor:N-methyl-D-aspartate receptor (AMPA: NMDA) at ZT18 vs. ZT6. The number of PV cells and PV/PNN cells containing orthodenticle homeobox 2 (OTX2), which maintains PNNs, showed a strong trend toward an increase from ZT6 to ZT18. Diurnal fluctuations in PNNs and PV cells are expected to alter cortical excitatory:inhibitory balance and provide new insights into treatments for diseases impacted by disturbances in sleep and circadian rhythms.

Expanding the Frontiers of Treatment: Cryoablation of an Ovarian Mass.

The ovaries are a common site of metastasis from a variety of solid organ malignancies. These tumors most commonly originate from the gastrointestinal tract. Neuroendocrine tumors of the small bowel are unrelenting in their tendency to exhibit this type of distant spread, which poses a challenge for curative treatment. Whether metastatic disease to the ovary or primary ovarian malignancy, this is a major cause of morbidity and mortality for women of various ages. Currently, a mainstay of palliative treatment for advanced-stage disease resides in surgical debulking and chemotherapy. At times, these patients may not be surgical candidates due to various reasons which may include a large disease burden. Computed tomography-guided percutaneous cryoablation is a minimally invasive technique that has shown promise in treating solid organ metastatic lesions by exposing them to lethal temperatures. We describe a novel technique of palliative cryoablation of a primary small bowel carcinoid tumor that metastasized to the ovary. Hydrodissection was utilized to create a window for safe percutaneous treatment. At the end of freeze cycles, intraoperative CT was performed, demonstrating greater than 90% incorporation of the ovarian tumor within the margins of the lethal ice zone. Our team decided that this was a maximum percentage of freeze due to neighboring vessels and bowel. The patient tolerated this treatment well, and there were no reported post-operative complications. The procedure was clinically successful at shrinking the tumor as demonstrated on a nine-month follow-up CT. Percutaneous cryoablation is already a widely utilized method for treating tumors in various locations including the kidneys and liver. The application of cryoablation can be expanded as an effective and safe palliative technique for treating ovarian tumors. This may be especially useful in patients that are not surgical candidates.

Preoperative Anemia Treatment with Intravenous Iron Therapy in Patients Undergoing Abdominal Surgery: A Systematic Review.

INTRODUCTION: Preoperative anemia is associated with increased morbidity, mortality, and healthcare costs. As a result of the increased incidence of chronic blood loss and iron deficiency anemia in abdominal surgery patients and its impact on patient outcomes, we systematically evaluated the quality of evidence for preoperative intravenous (IV) administration of iron to patients with anemia undergoing major abdominal surgery with the focus on clinical outcomes. METHODS: In this systematic review, PubMed, Cochrane, The Cumulative Index to Nursing and Allied Health Literature, Web Of Science, and Excerpta Medica Database databases were searched up to 2019 using specific keywords. Inclusion criteria were patients that were over 18 years of age, underwent abdominal surgery, and received an IV iron treatment in the preoperative setting. RESULTS: The nine studies included in the final systematic review do not provide consistent evidence of a reduced incidence of allogeneic blood transfusions with preoperative IV iron administration. However, IV iron administration did consistently cause a significant increase in hemoglobin levels relative to oral iron therapy or no iron. CONCLUSION: Overall, these findings are consistent in that IV iron administration is highly effective at rapidly increasing hemoglobin levels in patients with iron deficiency anemia undergoing major abdominal surgery. Unfortunately, there is currently no evidence of reduced incidence of allogeneic blood transfusions or other enhanced outcomes.